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International Journal of Colorectal... Nov 2017Perianal fistulising Crohn's disease (PFCD) affects a third of Crohn's disease patients and represents a disabling phenotype with poor outcome. The anti-tumour necrosis... (Review)
Review
BACKGROUND
Perianal fistulising Crohn's disease (PFCD) affects a third of Crohn's disease patients and represents a disabling phenotype with poor outcome. The anti-tumour necrosis factor alpha (TNF) therapies have been shown to maintain clinical remission in a third of patients after 1 year of treatment. Maintenance therapy with systematic administration schedules confers greatest benefit, but exposes patients to risks/side effects of continued systemic use and led to consideration of local drug delivery (first described in 2000). In this review, we analyse all published articles on local anti-TNF therapy in the treatment of PFCD.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to systematically search Medline and Embase using the medical subject headings 'fistula', 'anus', 'Crohn disease', 'infliximab' and 'adalimumab'. This was combined with free text searches, e.g. 'local injection' and 'Crohn's perianal disease'. Studies/abstracts describing local injection treatment with anti-TNF were included in this review.
RESULTS
Six pilot studies including a total of 92 patients were included in this review. Outcomes reported were mostly clinical and included 'complete/partial response' to therapy and short-term results varied between 40 and 100%. There were no significant adverse events and the local injections were well tolerated.
CONCLUSIONS
There is paucity of data assessing this treatment modality. Local anti-TNF therapy appears safe, but outcome reporting is heterogeneous, subjective and long-term data are unavailable. Our review suggests a potential role may be in those in whom systemic treatment is contraindicated and calls for standardised reporting of outcomes in this field to enable better data interpretation.
Topics: Adalimumab; Crohn Disease; Gastrointestinal Agents; Humans; Infliximab; Injections, Intralesional; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 28900730
DOI: 10.1007/s00384-017-2899-0 -
Annals of Coloproctology Aug 2016Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We...
Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject.
PubMed: 27626027
DOI: 10.3393/ac.2016.32.4.156 -
Journal of Clinical Laboratory Analysis Feb 2020MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical...
BACKGROUND
MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical application is low.
METHODS
Detection of plasma miRNAs was optimized by analyzing factors influencing miRNA variance and myocardial infarction risk scores during analysis (extraction, reverse transcription, and real-time PCR) and pre-analysis (dietary status, anticoagulants, storage conditions, and hemolysis).
RESULTS
Regarding variable factors during analysis, the centrifugal column method was superior to Trizol LS reagent when extracting miRNA from plasma. Recovery rate was highest with plasma volumes of 200 and 300 µL. During analysis, the main source of miRNA detection inaccuracy was derived from RNA extraction (mainly organic extraction), and not reverse transcription or PCR. MiRNA variance could be reduced by use of an internal reference. During analysis, 95% of risk score variation fluctuated within a range of 6.267. The variable factors pre-analysis mainly involved dietary status, anticoagulant selection, and storage conditions. Hemolysis positively correlated with miRNA levels, but there was no significant change in risk score after internal reference calibration.
CONCLUSION
Preliminary standardization for miRNA detection provides a reference for clinical blood testing of miRNAs.
Topics: Adult; Aged; Anticoagulants; Blood Specimen Collection; Fasting; Female; Hemolysis; Humans; Male; MicroRNAs; Middle Aged; Myocardial Infarction; Real-Time Polymerase Chain Reaction; Reproducibility of Results
PubMed: 31617231
DOI: 10.1002/jcla.23058 -
World Journal of Gastroenterology May 2017Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main... (Review)
Review
Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation (LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Anti-tumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.
Topics: Algorithms; Anastomosis, Surgical; Cholangitis, Sclerosing; Colonoscopy; Colorectal Neoplasms; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Liver Failure; Liver Transplantation; Male; Mesalamine; Postoperative Period; Proctocolectomy, Restorative; Risk Factors; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 28566881
DOI: 10.3748/wjg.v23.i18.3214 -
Journal of Pharmaceutical Analysis Dec 2023Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP)...
Excessive -acetyl--benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The knockout mice () and liver-specific overexpression of () mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, mice were defended against liver damage caused by APAP overdose by inhibiting the glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.
PubMed: 38223455
DOI: 10.1016/j.jpha.2023.08.004 -
PloS One 2024The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was... (Comparative Study)
Comparative Study
The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.
Topics: Animals; Dogs; Cytokines; Dog Diseases; Anal Sacs; Male; Microbiota; Female; RNA, Ribosomal, 16S; Dermatitis, Atopic; Case-Control Studies; Bacteria
PubMed: 38814946
DOI: 10.1371/journal.pone.0298361 -
Journal of Pharmaceutical Analysis Dec 2023This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD).... (Review)
Review
This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including "inflammatory bowel disease", "medicinal plants", "natural molecules", "anti-inflammatory", and "ulcerative colitis", and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κβ-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments.
PubMed: 38223446
DOI: 10.1016/j.jpha.2023.09.012 -
Journal of Clinical Laboratory Analysis Apr 2022Cardiovascular disease (CVD) is the single biggest contributor to global mortality. CVD encompasses multiple disorders, including atherosclerosis, hypertension, platelet... (Review)
Review
BACKGROUND
Cardiovascular disease (CVD) is the single biggest contributor to global mortality. CVD encompasses multiple disorders, including atherosclerosis, hypertension, platelet hyperactivity, stroke, hyperlipidemia, and heart failure. In addition to traditional risk factors, the circulating microbiome or the blood microbiome has been analyzed recently in chronic inflammatory diseases, including CVD in humans.
METHODS
For this review, all relevant original research studies were assessed by searching in electronic databases, including PubMed, Google Scholar, and Web of Science, by using relevant keywords.
RESULTS
This review demonstrated that elevated markers of systemic bacterial exposure are associated with noncommunicable diseases, including CVD. Studies have shown that the bacterial DNA sequence found in healthy blood belongs mainly to the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla. In cardiac events, such as stroke, coronary heart disease, and myocardial infarction, the increased proportion of Proteobacteria and Actinobacteria phyla was found. Lipopolysaccharides are a major component of Proteobacteria, which play a key role in the onset of CVD. Moreover, recently, a study reported the lower cholesterol-degrading bacteria, including Caulobacterales order and Caulobacteraceae family were both considerably reduced in myocardial infarction.
CONCLUSION
Proteobacteria and Actinobacteria were shown to be independent markers of the risk of CVD. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis in CVD. However, the association between blood microbiota and CVD is still inconsistent. Thus, more deep investigations are required in future to fully understand the role of the bacteria community in causing and preventing CVD.
Topics: Bacteria; Cardiovascular Diseases; Dysbiosis; Humans; Microbiota; Myocardial Infarction; Stroke
PubMed: 35293034
DOI: 10.1002/jcla.24354 -
The Pan African Medical Journal 2019The whole of the lesions associated with Crohn's disease affecting the anal canal, the skin of the perineum, the bottom-rectum and the recto vaginal septum are referred...
The whole of the lesions associated with Crohn's disease affecting the anal canal, the skin of the perineum, the bottom-rectum and the recto vaginal septum are referred to as anoperineal lesions of Crohn's disease. The main types of primary lesions include ulcerations, suppurations and stenoses. Crohn's disease-like anoperineal lesions are often suspected in patients with severe inflammatory process, peri-anal skin thickening, œdematous marisques, multiple lesions and lesions extending above pectineal line. Fistulas usually originate from an ulceration or a scar rather than the crypts of the anal canal. Elementary lesions of Crohn's disease are rarely isolated and they are, in most cases, combined lesions. The presence of a stenosis of the anal canal or of the rectum is very often associated with an inflammatory and suppurative process. Anal ulcerations are complicated with suppuration in half of the cases. We report the case of 45-year old woman treated for autoimmune thyroiditis and vitiligo who presented with knife-cut painful perineal ulcerations. The patient reported episodes of diarrhea during interview. Histological examination of skin lesions showed epitheliogigantocellular granuloma without caseous necrosis and digestive exploration suggested Crohn's disease which was confirmed with histology.
PubMed: 31692744
DOI: 10.11604/pamj.2019.33.231.17761 -
Thorax May 1970Cavitation in pulmonary metastases is more common than might be supposed from the small number of cases (75) previously reported. Twenty-five cases of cavitary pulmonary...
Cavitation in pulmonary metastases is more common than might be supposed from the small number of cases (75) previously reported. Twenty-five cases of cavitary pulmonary metastases were seen at the London Chest Hospital from 1964 to 1969. The primary sites were the large intestine (8), opposite lung (4), cervix (3), stomach, oesophagus, pancreas, and larynx (2 each) and anal canal and kidney (1 each). The size of the cavities ranged from 1·0 to 6·0 cm., and their wall thickness from 0·3 to 2·5 cm. Only in three cases was there an identifiable communication with the bronchial tree and only in these three cases were neoplastic cells found in the sputum. The main microscopic feature was vascular invasion, which was found in the vicinity of every metastasis; thrombosis was seen in 14 cases. It seems that the principal cause of necrosis and subsequent cavitation in metastatic tumours of the lung is interference with their blood supply by vascular involvement.
Topics: Adenocarcinoma; Adult; Aged; Bronchi; Cecal Neoplasms; Colonic Neoplasms; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Necrosis; Neoplasm Metastasis; Pulmonary Artery; Pulmonary Circulation; Radiography; Thrombosis
PubMed: 5452295
DOI: 10.1136/thx.25.3.375