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Frontiers in Immunology 2021Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It... (Review)
Review
Parasitic helminths, comprising the flatworms (tapeworms and flukes) and nematodes (roundworms), have plagued humans persistently over a considerable period of time. It is now known that the degree of exposure to these and other pathogens inversely correlates with the incidence of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. Accordingly, there has been recent increased interest in utilizing active helminth worm infections and helminth-derived products for the treatment of human autoimmune and inflammatory diseases and to alleviate disease severity. Indeed, there is an accumulating list of novel helminth derived molecules, including proteins, peptides, and microRNAs, that have been shown to exhibit therapeutic potential in a variety of disease models. Here we consider the blood-dwelling schistosome flukes, which have evolved subtle immune regulatory mechanisms that promote parasite survival but at the same time minimize host tissue immunopathology. We review and discuss the recent advances in using schistosome infection and schistosome-derived products as therapeutics to treat or mitigate human immune-related disorders, including allergic asthma, arthritis, colitis, diabetes, sepsis, cystitis, and cancer.
Topics: Animals; Biological Products; Disease Management; Disease Models, Animal; Humans; Immune System Diseases; Immunologic Factors; Immunomodulation; Mice; Recombinant Proteins; Schistosoma
PubMed: 33692793
DOI: 10.3389/fimmu.2021.619776 -
Journal of Clinical Oncology : Official... Aug 2021BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of...
PURPOSE
BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.
METHODS
We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.
RESULTS
Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.
CONCLUSION
Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
Topics: Adolescent; Adult; Aged; Cystitis; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Prospective Studies; T-Lymphocytes, Cytotoxic; Vascularized Composite Allotransplantation; Young Adult
PubMed: 33929874
DOI: 10.1200/JCO.20.02608 -
Neurogastroenterology and Motility Oct 2012Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial... (Review)
Review
BACKGROUND
Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis.
PURPOSE
The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared.
Topics: Humans; Irritable Bowel Syndrome; Somatoform Disorders
PubMed: 22863120
DOI: 10.1111/j.1365-2982.2012.01993.x -
Journal of Cellular and Molecular... Feb 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder pain/discomfort, urgency, urinary frequency, pelvic pain and nocturia. Although the pathophysiology of IC/BPS is not fully understood, the hypothesis suggests that mast cell activation, glycosaminoglycan (GAG) layer defects, urothelium permeability disruption, inflammation, autoimmune disorder and infection are potential mechanisms. Mesenchymal stem cells (MSCs) have been proven to protect against tissue injury in IC/BPS by migrating into bladders, differentiating into key bladder cells, inhibiting mast cell accumulation and cellular apoptosis, inhibiting inflammation and oxidative stress, alleviating collagen fibre accumulation and enhancing tissue regeneration in bladder tissues. In addition, MSCs can protect against tissue injury in IC/BPS by secreting various soluble factors, including exosomes and other soluble factors, with antiapoptotic, anti-inflammatory, angiogenic and immunomodulatory properties in a cell-to-cell independent manner. In this review, we comprehensively summarized the current potential pathophysiological mechanisms and standard treatments of IC/BPS, and we discussed the potential mechanisms and therapeutic effects of MSCs and MSC-derived exosomes in alleviating tissue injury in IC/BPS models.
Topics: Cystitis, Interstitial; Exosomes; Humans; Mesenchymal Stem Cells; Pelvic Pain; Urinary Bladder
PubMed: 34953040
DOI: 10.1111/jcmm.17132 -
Veterinary Immunology and... May 1989More than 2000 cats sent for necropsy in order to provide a diagnosis were investigated immunohistologically using paraffin sections for the presence of a persistent... (Review)
Review
More than 2000 cats sent for necropsy in order to provide a diagnosis were investigated immunohistologically using paraffin sections for the presence of a persistent infection with feline leukemia virus (FeLV). The spectrum of neoplastic and non-neoplastic diseases associated significantly with FeLV infection was determined statistically. Three-quarters of the cats with persistent FeLV infections died of non-neoplastic diseases and about 23% died of tumors, nearly exclusively those of the leukemia/lymphoma disease complex. A strong association with liver degeneration, icterus and a FeLV-associated enteritis was found in addition to the known association with non-neoplastic diseases and conditions such as anemia, bacterial secondary infections and respiratory tract inflammations due to the immunosuppressive effect of FeLV, hemorrhages and feline infectious peritonitis. Surprisingly, diseases and conditions like feline infectious panleukopenia, enteritis (of other types than FeLV-associated enteritis and feline infectious panleukopenia), glomerulonephritis, uremia and hemorrhagic cystitis were not associated with persistent FeLV infection. Another unexpected finding was that most pathogenic infectious agents demonstrated in the cats were not FeLV-associated either. Thus, immunosuppression due to FeLV infection seems to make the animals susceptible to certain pathogenic infectious agents, but not to the majority.
Topics: Anemia; Animals; Bacterial Infections; Cat Diseases; Cats; Enteritis; Jaundice; Leukemia; Leukemia Virus, Feline; Liver Diseases; Neoplasms; Retroviridae Infections
PubMed: 2549696
DOI: 10.1016/0165-2427(89)90132-3 -
SAGE Open Medicine 2022This systematic review aimed to evaluate the efficacy of different non-steroidal anti-inflammatory drugs therapy (monotherapy or combined with antibiotics) against... (Review)
Review
Efficacy and safety of different therapies of non-steroidal anti-inflammatory drugs against antibiotic monotherapy in the treatment of uncomplicated lower urinary tract infection: A systematic review.
This systematic review aimed to evaluate the efficacy of different non-steroidal anti-inflammatory drugs therapy (monotherapy or combined with antibiotics) against antibiotics monotherapy to understand the possible role of non-steroidal anti-inflammatory drugs in managing uncomplicated urinary tract infections and reduce overall antibiotic prescription. We searched four databases: PubMed, EMBASE, Scopus, and Cochrane CENTRAL. We included randomized controlled trials, which had included non-pregnant females above 18 years, published from 2010 to 2020 AD in the English language. We assessed risk of bias (ROB) using COCHRANE ROB version 2.0. We synthesized the conclusion from low ROB studies. Among five included studies, four studies compared non-steroidal anti-inflammatory drugs monotherapy against antibiotics monotherapy, and one study compared non-steroidal anti-inflammatory drugs + antibiotic therapy against antibiotic monotherapy. All studies with low ROB showed significantly higher events of symptom resolution by day 7 with antibiotic monotherapy compared to non-steroidal anti-inflammatory drugs monotherapy. Overall, adverse events were not significantly different in two of three low risk of bias studies; however, one study reported significantly higher adverse effects with non-steroidal anti-inflammatory drugs. Non-urinary tract infection-related adverse events were more common than urinary tract infections-related adverse events in both non-steroidal anti-inflammatory drugs and antibiotic groups. Urinary tract infection-related adverse events were higher in the non-steroidal anti-inflammatory drugs group compared to antibiotics. For every 20-60 participants treated, one would develop pyelonephritis additionally in non-steroidal anti-inflammatory drugs compared to antibiotics. Antibiotics were superior to non-steroidal anti-inflammatory drugs for treating uncomplicated lower urinary tract infections. However, further studies regarding the characteristics of patients likely to develop pyelonephritis on non-steroidal anti-inflammatory drugs monotherapy, and the effectiveness and safety of a combination of non-steroidal anti-inflammatory drugs and antibiotics therapy are essential to reduce the burden of antibiotics and their associated problems.
PubMed: 36081673
DOI: 10.1177/20503121221122392 -
Therapeutic Advances in Urology 2021Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating, systemic pain syndrome with a cardinal symptom of bladder related pain with associated systemic... (Review)
Review
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating, systemic pain syndrome with a cardinal symptom of bladder related pain with associated systemic symptoms. It is characterized by an inflammation that partially or completely destroys the mucus membrane and can extend into the muscle layer; however, the etiology and pathogenesis is still enigmatic. It has been suggested that mast cell activation, defects in the glycosaminoglycan layer, non-functional proliferation of bladder epithelial cells, neurogenic inflammation, microvascular abnormalities in the submucosal layer, autoimmunity and infectious causes may cause BPS/IC. Available treatment options include general relaxation techniques, patient education, behavioral treatments, physical therapy, multimodal pain therapy, oral (amitriptyline, cimetidine, hydroxyzine) and intravesical treatments (heparin, lidocaine, hyaluronic acid and chondroitin sulfate), hydrodistension and other more invasive treatments. Available treatments are mostly not based on a high level of evidence. Lack of understanding of disease mechanisms has resulted in lack of targeted therapies on this area and a wealth of empirical approaches with usually inadequate efficacy. The aim of this article is to review the available evidence on the pathophysiological mechanisms of BPS/IC as they relate to available treatment options.
PubMed: 34178118
DOI: 10.1177/17562872211022478 -
Cell Reports. Medicine Jul 2023Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a...
Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQβ1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10) and of HLA-DPβ1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10). The three HLA-DQβ1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation.
Topics: Humans; Cystitis, Interstitial; Genome-Wide Association Study; Major Histocompatibility Complex; Chromosomes; Amino Acids
PubMed: 37467720
DOI: 10.1016/j.xcrm.2023.101114 -
Antibiotics (Basel, Switzerland) Feb 2022Recurrent cystitis (RC) has rarely been studied; its management varies and research on a holistic approach of these patients is scarce. We attempted to characterize...
Recurrent cystitis (RC) has rarely been studied; its management varies and research on a holistic approach of these patients is scarce. We attempted to characterize patients suffering from RC and investigated their current care pathways, aiming to offer customized and autonomous management. In this paper, we present a descriptive, single-center, cross-sectional study of women presenting with RC at an infectious disease (ID) clinic. A questionnaire was developed and was completed by ID physicians during patient visits. From October 2016 to January 2019, 202 women were included (mean age 59 years). Sexual intercourse, stress and diarrhoea/digestive symptoms were reported as trigger factors by 35%, 34% and 19% of patients, respectively. A majority (54%) were at risk for complications and were those more exposed to inappropriate antibiotic prescriptions. In total, 56% of women suffered from more than 10 episodes/year and 48% suffered from relapses, mainly due to . Genitourinary syndrome of menopause (GSM) was a frequent complaint (74.5% of women). Fluoroquinolones and 3rd generation cephalosporins were prescribed in 38% and 30% of women, respectively. Most women wished for non-antimicrobial approaches and autonomy. Patients require comprehensive, tailored care in order to benefit from a broader range of treatment options in compliance with recommendations.
PubMed: 35203871
DOI: 10.3390/antibiotics11020269 -
MSphere Oct 2023is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall...
is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species is poorly understood within this age group. To investigate whether uropathogenic (UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding allele is substantially more prevalent in invasive UPEC from adults, we found was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that 30, an allele of the fimbrial gene often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the 30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by , are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children.
Topics: Adult; Humans; Child; United States; Uropathogenic Escherichia coli; Anti-Bacterial Agents; Escherichia coli Infections; Genetic Markers; Virulence Factors; Urinary Tract Infections; Pyelonephritis; Genomics
PubMed: 37581436
DOI: 10.1128/msphere.00184-23