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Analytical Cellular Pathology... 2023Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is...
BACKGROUND
Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients.
METHODS
The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG.
RESULTS
Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; < 0.05). The expression of RANKL, TNF-, IL-1, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group ( < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM.
CONCLUSIONS
DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1, IL-6, and TNF-) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.
Topics: Humans; Tumor Necrosis Factor-alpha; Interleukin-6; Aggrecans; Reactive Oxygen Species; Cartilage, Articular; Diabetes Mellitus
PubMed: 37197158
DOI: 10.1155/2023/7573165 -
Journal of Indian Association of... 2017To assess the modifications in the technique of laparoscopic-assisted anorectal pull-through (LAARP) practiced at our institute and to analyze the postoperative outcome...
AIM
To assess the modifications in the technique of laparoscopic-assisted anorectal pull-through (LAARP) practiced at our institute and to analyze the postoperative outcome and associated complications.
MATERIALS AND METHODS
A retrospective study was done to analyze the results for LAARP procedure done for high anorectal malformations (ARMs) from January 2001 to May 2016. A total of 68 patients had undergone LAARP, with 62 male and 6 female children. Staged procedure was done in 55 patients and one child with rectovestibular fistula of 5 months of age had a single-stage procedure. Technical modifications such as traction over the fistula which helps in identification and dissection of the puborectalis muscle, dividing the fistula without ligation, railroading with Hegar's dilators over the suction cannula which creates adequate pull-through channel, have helped save time and make the procedure simpler. The patients were followed up with clinical evaluation and continence scoring.
RESULTS
All the patients withstood surgery well. One patient with rectovesical fistula required conversion to gain adequate length of the distal rectum, for whom the colostomy was closed and relocated at splenic flexure level. The complications were mucosal prolapse (8 cases), anal stenosis (5), adhesive obstruction (2), distal rectal necrosis (3), and urethral diverticulum (2). The progress has been satisfactory and weight gain is adequate. 71.15% patients had good continence on follow-up.
CONCLUSION
LAARP procedure is safe for high ARMs with good continence and correctable side effects. It has completely replaced posterior sagittal anorectoplasty procedure for high anomalies in our practice.
PubMed: 28413307
DOI: 10.4103/jiaps.JIAPS_266_16 -
BMC Complementary Medicine and Therapies Jan 2021Ulcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates...
BACKGROUND
Ulcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory cells, leading to ulceration and haemorrhage through cytotoxic reactive oxygen species. 6-Paradol, a dietary component in several plants belonging to the Zingiberaceae family, has shown anti-inflammatory and antioxidant activities. Current study evaluates the effect of 6-paradol in amelioration of ulcerative colitis in rats for the first time.
METHODS
6-Paradol (95% purity) was obtained from seeds of Aframomum melegueta. Rats were divided randomly into six groups (n = 8). Group one was administered normal saline; group two was treated with the vehicle only; group three, sulfasalazine 500 mg/kg; and groups four, five, and six, were given 6-paradol (50, 100, 200, respectively) mg/kg orally through gastric gavage for 7 days. Colitis was induced on 4th day by intrarectal administration of 2 ml acetic acid (3%), approximately 3 cm from anal verge. On 8th day, rats were sacrificed, and distal one-third of the colon extending proximally up to 4 cm from anal orifice was taken for biochemical and gross examination. Two centimetres of injured mucosal portion was taken for histopathological investigations. SPSS (ver.26) was used for statistical analysis.
RESULTS
Colonic and serum glutathione (GSH) levels decreased, while colonic and serum malondialdehyde (MDA), colonic myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6), serum tumour necrosis factor-α (TNF-α) levels, and colon weight to length ratio were increased significantly in the colitis untreated group compared to normal control. Treatment with 6-paradol considerably improved all these parameters, especially at a dose of 200 mg/kg (p < 0.001), revealing non-significant differences with sulfasalazine 500 mg/kg and normal control (p = 0.998). Sulfasalazine and 6-paradol in a dose dependent manner also markedly reversed mucosal oedema, atrophy and inflammation, cryptic damage, haemorrhage, and ulceration. There were non-significant differences between low and medium doses and between medium and high doses of 6-paradol for IL-6 and serum MDA levels.
CONCLUSION
6-Paradol demonstrated protection against acetic acid-induced ulcerative colitis, probably by anti-inflammatory and antioxidant actions.
Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Colitis, Ulcerative; Colon; Glutathione; Guaiacol; Ketones; Male; Rats; Rats, Sprague-Dawley; Seeds; Zingiberaceae
PubMed: 33441125
DOI: 10.1186/s12906-021-03203-7 -
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 -
Analytical Cellular Pathology... 2023The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA...
BACKGROUND
The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA.
METHODS
miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin-eosin (HE) and safranin O-fast Green (S-O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage.
RESULTS
The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment.
CONCLUSIONS
miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.
Topics: Rats; Animals; MicroRNAs; Fibroblast Growth Factor 9; Osteoarthritis; Inflammation; Apoptosis; Interleukin-6; Chondrocytes; Interleukin-1beta
PubMed: 37035017
DOI: 10.1155/2023/5911546 -
Clinical Gastroenterology and... Jan 2023Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively...
BACKGROUND & AIMS
Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis.
METHODS
Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis.
RESULTS
Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05).
CONCLUSIONS
This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.
Topics: Humans; Pouchitis; Colitis, Ulcerative; Incidence; Cohort Studies; Proctocolectomy, Restorative; Denmark; Colonic Pouches
PubMed: 35525393
DOI: 10.1016/j.cgh.2022.04.015 -
Annals of Coloproctology Feb 2021Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal... (Review)
Review
Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal surgeons. Accurately classifying a perianal fistula is the initial step in its management in CD patients. Surgical management is selected based on the type of perianal fistula and the presence of rectal inflammation; it includes fistulotomy, fistulectomy, seton procedure, fistula plug insertion, video-assisted ablation of the fistulous tract, stem cell therapy, and proctectomy with stoma creation. Perianal fistulas are also managed medically, such as antibiotics, immunomodulators, and biologics including anti-tumor necrosis factor-alpha agents. The current standard treatment of choice for perianal fistula in CD patients is the multidisciplinary approach combining surgical and medical management; however, the rate of long-term remission is low and is reported to be 50% at most. Therefore, the optimum management strategy for perianal fistulas associated with CD remains controversial. Currently, the goal of management for CD-related perianal fistulas are controlling symptoms and maintaining long-term anal function without proctectomy, while monitoring progression to anorectal carcinoma. This review evaluates perianal fistula in CD patients and determines the optimal surgical management strategy based on recent evidence.
PubMed: 33730796
DOI: 10.3393/ac.2021.02.08 -
Contrast Media & Molecular Imaging 2022To explore the efficacy of Chinese herbal fumigation and sitz-bath combined with red ointment in the treatment of postoperative wound healing and pain control in anal... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the Effectiveness of a Combination of Chinese Herbal Fumigation Sitz-Bath and Red Ointment in Managing Postoperative Wound Healing and Pain Control in Anal Fistula Patients.
OBJECTIVE
To explore the efficacy of Chinese herbal fumigation and sitz-bath combined with red ointment in the treatment of postoperative wound healing and pain control in anal fistula patients.
METHODS
A total of 118 anal fistula patients were selected as the study population, randomly divided into two groups, i.e., the research group ( = 60) and the control group ( = 60). The control group was treated with red ointment therapy for postoperative wound healing and pain while the research group was treated with a combination of ointment and traditional Chinese medicine fumigation sitz-bath, Postoperative wound healing, pain control, and safety evaluation were compared between the two groups. Results. The total effective rate in the research group was 96.67%, which was significantly higher than that in the control group (93.10%), and the difference was statistically significant ( < 0.05). The VAS scores and postoperative wound healing times in the research group were significantly lower than those in the control group. The difference was statistically significant ( < 0.05). A day after postoperative treatment, there was no significant difference ( > 0.05) in TNF- and IL-6 levels between the two study groups; however, from day 3 to day 14 the levels were statistically different. TNF- and IL-6 levels in research group were significantly lower than those in the control group. The difference was statistically significant ( < 0.05). The incidence of postoperative complications in the research group at 6.67% was statistically significant ( < 0.05), significantly lower than 13.79% in the control group. Conclusion. Postoperative intervention with Chinese herbal fumigation and sitz-bath combined with red ointment can effectively reduce the wound healing duration and lower the degree of pain experienced by anal fistula patients, thereby improving their quality of life.
Topics: China; Fumigation; Humans; Interleukin-6; Ointments; Pain; Quality of Life; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha; Wound Healing
PubMed: 36176927
DOI: 10.1155/2022/1905279 -
Frontiers in Medicine 2019Quality of life after ileal pouch-anal anastomosis (IPAA) surgery is generally good. However, patients can be troubled by pouch-related symptoms and pouch disorders that... (Review)
Review
Quality of life after ileal pouch-anal anastomosis (IPAA) surgery is generally good. However, patients can be troubled by pouch-related symptoms and pouch disorders that can be inflammatory, mechanical/surgical, and functional. Management of patients with IPAA begins with measures to maintain a healthy pouch such as optimizing pouch function, providing tailored advice on a healthy diet and lifestyle, screening for and addressing metabolic complications of IPAA, pouch surveillance, and risk stratification for risk of pouchitis and pouch failure. Pouchitis is the most common inflammatory disorder. Primary pouchitis is a spectrum currently classified into three progressive phases-an antibiotic-responsive, an antibiotic-dependent, and an antibiotic-refractory phase. It is predominately microbially mediated in acute antibiotic-responsive pouchitis and predominately immune mediated in chronic antibiotic-refractory pouchitis (CARP). Secondary prophylaxis is recommended for recurrent antibiotic-responsive and for antibiotic-dependent pouchitis. Secondary causes of antibiotic-refractory pouchitis should be ruled out before a diagnosis of CARP is made. CARP is best classified as primary sclerosing cholangitis associated, immunoglobulin G4-associated, and autoimmune. Primary sclerosing cholangitis-associated CARP can be treated with budesonide or oral vancomycin. Early recognition of immunoglobulin G4-associated pouchitis minimizes ineffective antibiotic use. Autoimmune CARP can be managed in a manner similar to UC. The current place of immunosuppressives in the treatment algorithm depends on availability and early access to biological agents. Vedolizumab and ustekinumab are the preferred first- and second-line biologics for autoimmune CARP owing to their efficacy, better side effect profile, and low immunogenicity and need for concomitant immunomodulatory therapy. Antitumor necrosis factor should be reserved for autoimmune CARP failing the above and for CD of the pouch. There are no guidelines for the surveillance of pouches for dysplasia. Incidence varies based on a patient's risk. Since incidence is low, a risk-stratified approach is recommended.
PubMed: 32064264
DOI: 10.3389/fmed.2019.00337 -
Journal of Pharmaceutical and... Jan 2014Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that modulate immune responses in various diseases. Due their...
Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low-molecular-weight peptides that modulate immune responses in various diseases. Due their complexity, standardized methods to identify their physicochemical properties and determine that production batches are biologically active must be established. We aimed to develop and validate a size exclusion ultra performance chromatographic (SE-UPLC) method to characterize Transferon™, a DLE that is produced under good manufacturing practices (GMPs). We analyzed an internal human DLE standard and 10 representative batches of Transferon™, all of which had a chromatographic profile characterized by 8 main peaks and a molecular weight range between 17.0 and 0.2kDa. There was high homogeneity between batches with regard to retention times and area percentages, varying by less than 0.2% and 30%, respectively, and the control chart was within 3 standard deviations. To analyze the biological activity of the batches, we studied the ability of Transferon™ to stimulate IFN-γ production in vitro. Transferon™ consistently induced IFN-γ production in Jurkat cells, demonstrating that this method can be included as a quality control step in releasing Transferon™ batches. Because all analyzed batches complied with the quality attributes that were evaluated, we conclude that the DLE Transferon™ is produced with high homogeneity.
Topics: Adjuvants, Immunologic; Cell Movement; Chemotaxis; Chromatography, High Pressure Liquid; Cytokines; Humans; Inflammation; Interferon-gamma; Jurkat Cells; Leukocytes; Molecular Weight; Peptides; Reproducibility of Results; Signal Transduction
PubMed: 24099727
DOI: 10.1016/j.jpba.2013.09.004