ABSTRACT
Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.
Subject(s)
Drainage , Fournier Gangrene , Humans , Fournier Gangrene/surgery , Drainage/methods , Male , Treatment Outcome , Middle Aged , Fasciitis, Necrotizing/surgery , Female , Adult , Debridement/methods , Skin , Abscess/surgeryABSTRACT
BACKGROUND: Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. SHORT CONCLUSION: MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.
Subject(s)
Crohn Disease , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Rectal Fistula , Humans , Quality of Life , Mesenchymal Stem Cell Transplantation/methods , Treatment Outcome , Rectal Fistula/therapy , Crohn Disease/therapyABSTRACT
OBJECTIVE: This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. MATERIALS AND METHODS: We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). RESULTS: Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. CONCLUSIONS: AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.
Subject(s)
Antirheumatic Agents , Autoimmune Diseases , COVID-19 Drug Treatment , Rheumatic Diseases , Antirheumatic Agents/therapeutic use , Humans , Incidence , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiologySubject(s)
Colonic Neoplasms , Laparoscopy , Colectomy , Colonic Neoplasms/surgery , Humans , Lymph Node Excision , Lymph Nodes/surgeryABSTRACT
Objective: To investigate the mechanism of action of peroxisome proliferator-activated receptor α (PPARα)-mediated CCAAT/enhancer binding protein homologous protein (CHOP) signaling molecule with response to inflammation in mice with acute liver failure. Methods: C57BL/6 mice were used as the research subjects, and D-galactose (D-GalN) combined with lipopolysaccharide (LPS) was injected intraperitoneally to establish a mouse model of acute liver failure. PPARα was activated by Wy-14643. CHOP expression was promoted by plasmids. Liver pathological changes and serum transaminases (ALT and AST) were detected in mice to evaluate liver function. The mRNA expression level of inflammatory factors in liver tissue was detected by real-time fluorescence quantitative PCR. LPS-stimulated macrophage was used to establish an inflammation model. PPARα and CHOP expression was inhibited by siRNA. The mRNA expression level of inflammatory factors in the cells was detected by real-time fluorescence quantitative PCR. Results: Promoted PPARα activation had inhibited liver hemorrhage and inflammation in mice with acute liver failure induced by D-GalN/LPS. In addition, the serum level of transaminases and genetic level of inflammatory factors in liver tissues were reduced (P < 0.01). CHOP accelerated expression had reversed the hepatoprotective effect of PPARα activation, aggravated liver injury, and increased inflammatory factors expression (P < 0.01). At the cellular level, the inhibition of PPARα activation had accelerated the increase of inflammatory factors (P < 0.01), while the inhibition of CHOP activation had all over again decreased the inflammatory factors (P < 0.01). Conclusion: PPARα and CHOP are important signaling molecules to regulate the inflammatory response in acute liver failure and liver injury. PPARα acceleration can down-regulate CHOP to inhibit inflammatory factors, which might play a protective role in mice with acute liver failure.
Subject(s)
Liver Failure, Acute/pathology , PPAR alpha/metabolism , Transcription Factor CHOP/metabolism , Animals , Inflammation , Lipopolysaccharides , Liver , Liver Failure, Acute/metabolism , Mice , Mice, Inbred C57BLABSTRACT
This article aims to explore the expression and mechanism of miR-10a-5p in pancreatic cancer. MiR-10a-5p mimic, MiR-10a-5p inhibitor and negative control were transfected into human pancreatic cancer cell line SW1990. Real-time quantitative PCR technology was used to analyze the expression level of miR-10a-5p in pancreatic cancer tissues and cells. The proliferation, invasion and apoptosis of SW1990 cells in each group were detected by CCK-8 analysis, Transwell analysis, TUNEL method and flow cytometry. Targetscan7.2 was used to predict the target protein of MiR-10a-5p, and the expression of related proteins was detected by Western blot analysis. The results showed that the expression of miR- 10a-5p in cancer tissues of patients with pancreatic cancer was significantly higher than that in adjacent tissues (P <0.05). The expression of miR-10a-5p in cancer cells increased significantly, which could promote the proliferation and invasion of SW1990 cells and inhibit apoptosis (P <0.05). Overexpression of miR-10a-5p can regulate the expression of BDNF and SEMA4C. miR-10a-5p can promote the occurrence and development of pancreatic cancer by regulating the BDNF / SEMA4C pathway, and may become a molecular target for the diagnosis and treatment of pancreatic cancer in the future.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , MicroRNAs/genetics , Pancreatic Neoplasms/pathology , Semaphorins/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Signal TransductionABSTRACT
PURPOSE: Hypoxia is an indispensable factor in the progression of metastasis. Hypoxia inducible factor-1α (HIF-1α), the core element in generating the hypoxia response, induces invasion and metastasis by promoting epithelial-mesenchymal transition (EMT). This study explored the underlying mechanism of hypoxia associated with the invasion and metastasis of gastric cancer (GC). METHODS: Six methods were employed to assess the function of the long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) including gene silencing, RT-PCR, the separation of nuclear and cytoplasmic fractions, scrape motility assay, transwell migration assay, and Western-blot. RESULTS: LncRNA PCGEM1 was overexpressed in GC cells and tissues, and was induced by hypoxia in GC cells. Additional experiments confirmed that the knockdown of PCGEM1 significantly repressed the invasion and metastasis of GC cells. SNAI1, a key transcription factor of EMT, was regulated by PCGEM1. Overexpression of SNAI1 rescued the inhibition of PCGEM1-knockdown during the invasion and metastasis of GC cells. In addition, PCGEM1 and SNAI1 jointly affected the biomarkers of EMT. CONCLUSION: Our findings indicated that PCGEM1 is a hypoxia-responsive lncRNA, and contributes to the invasion and metastasis of GC. The potential mechanism is attributed to the regulation of EMT by PCGEM1 and its influence on the expression of SNAI1.
Subject(s)
Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Hypoxia/physiopathology , RNA, Long Noncoding/genetics , Snail Family Transcription Factors/metabolism , Stomach Neoplasms/pathology , Apoptosis , Epithelial-Mesenchymal Transition , Humans , Neoplasm Invasiveness , Snail Family Transcription Factors/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To explore the effect of hypoxia on the Twist1 expression in epithelial-mesenchymal transition of the cervical cancer cells. MATERIALS AND METHODS: In this study, we simulated the normoxia and hypoxia environment, where HeLa cells were cultured, respectively. Cell invasion ability was measured by the transwell assay, while the GLI-1 protein and mRNA expressions were measured by Real-time polymerase chain reaction (RT-PCR) and Western blot assays. After that, HeLa cells were transfected with the GLI-1-specific siRNA, followed by the measurement of mRNA and protein expressions using RT-PCR and Western blot assays, as well as the cell invasion ability by the transwell assay. RESULTS: We found that in hypoxic environment, GLI-1 was up-regulated in HeLa cells, with enhanced invasion ability. However, silencing the expression of GLI-1 could reverse the up-regulation of GLI-1 compromising the invasion ability of HeLa cells. CONCLUSIONS: Hypoxia may account for the increased invasion of HeLa cells, which is realized by the up-regulated GLI-1.
Subject(s)
Nuclear Proteins/metabolism , Tumor Hypoxia , Tumor Microenvironment , Twist-Related Protein 1/metabolism , Uterine Cervical Neoplasms/metabolism , Cell Movement , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Neoplasm Invasiveness , Nuclear Proteins/genetics , Signal Transduction , Twist-Related Protein 1/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein GLI1/metabolismABSTRACT
Objective: To investigate the effect of GHRH on the cognitive function of OSAHS patients by detecting the serum GHRH levels and assessing their cognitive function in patients with OSAHS. Methods: A total of 70 moderate-severe OSAHS patientsand 32 adults with snoring from October 2013 to May 2017 were enrolled for overnight polysomnography(PSG) and cognitive function assessment. Blood samples were taken at the next morning and serum GHRH levels were measured by ELISA. Results: There was no significant difference between OSAHS group (318.73±186.66)pg/ml and control group (291.48±147.36)pg/ml. Compared with control group, the serum GHRH levels were significantly increased in OSAHS patients without cognitive impairment (370.31±197.33)pg/ml, and evidently decreased in those with cognitive impairment (193.63±70.97)pg/ml (both P<0.05). The cognitive function of OSAHS patients was influenced by serum GHRH levels (OR=0.42, 95%CI: 0.24-0.73), body mass index (OR=2.23, 95%CI: 1.03-4.79), and daily sleepiness score (OR=1.80, 95%CI: 1.04-3.09). Conclusion: Serum GHRH levels in patients with moderate-severe OSAHS may play a protective role in patients' cognitive function.
Subject(s)
Cognition , Body Mass Index , Growth Hormone-Releasing Hormone , Humans , Polysomnography , Sleep Apnea, Obstructive , Sleep Stages , SnoringABSTRACT
Triple negative breast cancer (TNBC) is associated with aggressive behaviour and poor prognosis, but has limited treatment options. To explore novel and effective therapies against TNBC, we retrospectively analyzed the efficacy of neoadjuvant intra-arterial chemotherapy through the superior epigastric artery in the treatment of locally advanced TNBC. Fifty-one locally advanced TNBC patients who received this neoadjuvant therapy from Mar 2001 to Mar 2012 were included in this study. The superior epigastric artery was selected for cannulation to deliver chemotherapy drugs. The regimen for intra-arterial chemoinfusion consisted of 75 mg/m2 epirubicin and 75 mg/m2 docetaxel. Clinical and pathological tumor responses, disease free survival (DFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed. In 51 patients treated with neoadjuvant intra-arterial chemoinfusion through the superior epigastric artery, the overall response rate (ORR) was 84.3%; 16 patients achieved pathological complete response (pCR). Following surgical treatment and adjuvant chemotherapy, 5-year DFS and OS were 72.4% and 75.9%, respectively, in the study population. In addition, this neoadjuvant approach showed favorable toxicity profiles. Moreover, patients who achieved pCR showed a superior survival outcome compared with those who did not. Cox regression analysis indicated that Ki-67 expression is an independent predictor for DFS and OS. Our results suggest that intra-arterial chemotherapy through the superior epigastric artery has great therapeutic potential for the treatment of locally advanced TNBC. This approach merits further clinical evaluation and may become a novel therapeutic option for locally advanced TNBC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Docetaxel/administration & dosage , Epigastric Arteries , Epirubicin/administration & dosage , Triple Negative Breast Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Disease-Free Survival , Docetaxel/therapeutic use , Epirubicin/therapeutic use , Female , Humans , Neoadjuvant Therapy , Remission Induction , Retrospective Studies , Survival Rate , Treatment Outcome , Triple Negative Breast Neoplasms/mortalityABSTRACT
OBJECTIVE: Although bariatric surgery including gastrectomy has recently emerged as a useful treatment for type 2 DM with obesity, it is not clear whether gastrectomy itself can have beneficial effects on glucose metabolism. Therefore, in this study, we investigated changes in blood glucose in patients with and without diabetes who underwent gastrectomy. METHODS: From Jan 2010 to May 2014, 77 patients with diabetes and 77 patients without diabetes who underwent gastrectomy at Chonbuk National University Hospital, South Korea, were included. We compared fasting plasma glucose levels and HbA1c value before and after gastric surgery. RESULTS: After gastrectomy, 59 patients (38.3%) showed reduced fasting plasma glucose levels at the 1 year point, and 80 patients (51.9%) exhibited reduced fasting plasma glucose at 3 years, irrespective of their diabetes status. Among 77 patients with diabetes, decreased fasting plasma glucose was observed in 22 (28.6%) and 46 patients (59.7%) 1 and 3 years after gastrectomy, respectively. In patients who exhibited reduced fasting plasma glucose after gastrectomy, the degree of reduced glucose was as follows: 56.4±48.5 vs 23.2±16.1 mg/dL after 1 year, 58.3±52.3 vs 18.4±13.7 mg/dL after 3 years, in DM and non-DM patient respectively. CONCLUSIONS: Although there was a significant drop in mean fasting glucose after gastrectomy, not all patients experienced a drop in fasting glucose. Gastrectomy did not show a consistent association with glucose reduction in patients with and without diabetes, and in about half of the patients, fasting plasma glucose levels increased after gastrectomy. Therefore, bariatric surgery including gastrectomy needs to be performed with care in diabetes, and glucose monitoring including oral glucose tolerance tests should be done for assessing or prediction of the glucose state after gastric surgery in non-DM patients.
ABSTRACT
The aim of the present study was to determine the anti-proliferative and pro-apoptotic effects of dihydromyricetin (DHM) on the AGS human gastric cancer cells and their underlying mechanisms. The effects of DHM on AGS cells were evaluated by using 3-(4, 5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase, and Annexin V/propidium iodide (PI) double-staining assays. The underlying mechanisms were determined by using quantitative real-time polymerase chain reaction. The results demonstrated that DHM significantly (P < 0.05) inhibited AGS cell proliferation and induced cell cytotoxicity in a dose- and time-dependent manner. Additionally, Annexin V/PI double-staining assay showed that DHM promoted cell apoptosis in both, early and late stages. Furthermore, DHM also regulated the expression of apoptotic genes such as p53 and B-cell lymphoma-2 (bcl-2) in a dose- and time-dependent manner. In conclusion, this is the first report demonstrating the anticancer and pro-apoptosis effects of DHM on AGS human gastric cancer cells. The results strongly suggest that DHM may be a potential therapeutic candidate for the treatment of gastric cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Flavonols/pharmacology , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Apoptosis/genetics , Apoptosis Regulatory Proteins/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Stomach Neoplasms/geneticsABSTRACT
BACKGROUND: Liver transplantation (LT) may induce the occurrence of diabetes mellitus. It can be speculated, however, that the LT may have a beneficial effect on glucose metabolism. We therefore conducted a study to examine the changing trends in blood glucose levels before and after LT in patients with prediabetes or type 2 diabetes. METHODS: In this observational study, we enrolled 47 patients (38 prediabetes and 9 diabetes) who underwent LT. We compared the blood glucose levels between the pre-transplantation (24 months) and the post-transplantation (36 months) periods and analyzed the diverse factors affecting glucose levels. RESULTS: The glucose regulation worsened and insulin dose increased in patients with diabetes, which was notably seen during the steroid maintenance period. Following steroid withdrawal, however, there was a decrease in the insulin dose in 55.6% of the patients, and 33.3% of the patients converted from insulin to oral agents. Of the patients with prediabetes, 55.3% developed new-onset diabetes after transplantation (NODAT). However, 18.4% achieved a recovery of glucose levels to normal range. Of the 21 NODAT patients, 52.4% achieved a recovery of glucose level to the prediabetes range after steroid withdrawal. There was a significant correlation between the old age and the persistence of NODAT (P < .05). CONCLUSIONS: LT may have a diverse effect on glycemia, which may lead to changes in glucose control methods. Therefore, glucose metabolism after LT may need to be differentiated by the underlying glucose disturbance status and the time after LT with or without steroid maintenance period.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Liver Failure/surgery , Liver Transplantation , Prediabetic State/blood , Adult , Cross-Sectional Studies , Diabetes Complications/therapy , Diabetes Mellitus, Type 2/complications , Female , Glucose Tolerance Test , Humans , Insulin/blood , Liver Failure/blood , Liver Failure/complications , Longitudinal Studies , Male , Middle Aged , Prediabetic State/complications , Retrospective Studies , Treatment OutcomeSubject(s)
Graves Disease/complications , Heart Diseases/etiology , Thrombosis/etiology , Aged , Diagnosis, Differential , Echocardiography, Transesophageal , Female , Heart Atria/diagnostic imaging , Heart Diseases/diagnosis , Heart Neoplasms/diagnosis , Humans , Myxoma/diagnosis , Thrombosis/diagnosis , Tomography, X-Ray ComputedABSTRACT
INTRODUCTION: Early and normative surgery is the only curative method for multiple endocrine neoplasia type 2 (MEN 2)-related medullary thyroid carcinoma (MTC). AIMS: To study the timing of prophylactic total thyroidectomy (TT) for MEN 2-related MTC with different RET mutations in a Chinese population, and to compare the sensitivity and accuracy of fully-automated chemiluminescence immunoassay (FACLIA) and radioimmunoassay (RIA) for serum calcitonin (Ct). METHODS: We collected 24 asymptomatic individuals from 8 unrelated Chinese families with MEN 2, and analyzed RET mutation and Ct levels. Then we performed TT on 17 of the 24 individuals, including TT (2/17), TT with bilateral level VI lymph-node dissection (B-LND(VI); 12/17) and TT with B-LND(VI) + modified unilateral/bilateral/local neck dissection (3/17). RESULTS: Histopathology revealed bilateral/unilateral MTC in 15/17 (88.2%; median diameter, 1.0 cm) and bilateral C-cell hyperplasia in 2/17 (11.8%; p.V292M/R67H/R982C and p.C618Y). Lymph-node metastasis/fibro-adipose tissue invasion (p.C634R) or solely fibro-adipose tissue invasion (p.C634Y) were found in 2/17 (11.8%). Elevated pre-surgical Ct (pre-Ct) was identified by FACLIA in 17/17 (median age, 24.0), while pre-Ct by RIA was found in only 6/15 (P < 0.001). The median follow-up was 22.0 months, during which 16/17 had no abnormality (one p.C634R individual had elevated Ct), and another 7 carriers still had consistently undetectable Ct by FACLIA. CONCLUSIONS: Our study highlights the importance and feasibility of individualized prophylactic TT for MEN 2-related MTC, based on predictive integrated screening of RET and pre-Ct levels. Besides, we recommend FACLIA to measure Ct for earlier diagnosis, treatment and follow-up monitoring of MTC.
Subject(s)
Calcitonin/blood , Carcinoma, Medullary/congenital , Multiple Endocrine Neoplasia Type 2a/surgery , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Adolescent , Adult , Asian People , Asymptomatic Diseases , Carcinoma, Medullary/diagnosis , Carcinoma, Medullary/prevention & control , Carcinoma, Medullary/surgery , Child , Child, Preschool , China , Female , Humans , Male , Middle Aged , Multiple Endocrine Neoplasia Type 2a/diagnosis , Multiple Endocrine Neoplasia Type 2a/genetics , Multiple Endocrine Neoplasia Type 2a/prevention & control , Mutation , Neck Dissection , Proto-Oncogene Mas , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/prevention & control , Young AdultABSTRACT
OBJECTIVE: In addition to tight glucose control, early intensive therapy has been reported to be more important for the prevention of diabetic micro- and macro-vascular complications. What is not known exactly is the quantitative difference according to timing delay in glucose control and whether early period control is really better than late control in terms of diabetic peripheral neuropathy. In this study, we investigated the effect of timing differences in glucose control on the peripheral nerves in an experimental diabetic model. METHODS: 5 groups (6-8 rats in each group) were comprised of normal glucose rats (designated control), rats with hyperglycemia (designated DM), rats with glucose control for the entire 28-week study period (designated DM + INS [W0-28]), rats with glucose control for the early 14-week period followed by hyperglycemia for the late 14-week period (designated DM + INS [W0-14]), and rats with hyperglycemia for the early 14-week period followed by glucose control in the late 14-week period (designated DM + INS [W15-28]). RESULTS: We found that the current perception threshold (CPT) was lower in the DM + INS (W0-28) and DM + INS (W15-28) groups than in the DM + INS (W0-14) or DM groups (P<0.05). The mean myelinated fiber area of the sciatic nerve was significantly greater in the DM + INS (W0-28) and DM + INS (W15-28) groups (63.5±2.32 and 60.1±2.14 um, respectively) than in the DM + INS (W0-14) or DM groups (55.5±2.81 or 51.5±2.64 um, respectively) (P<0.05), and the intraepidermal nerve fiber (IENF) density was significantly higher in the DM + INS (W0-28) and DM + INS (W15-28) groups (6.9±0.46 and 6.8±0.11, respectively) than in the DM + INS (W0-14) or DM groups (59.5±0.32 and 5.3±0.39/mm, respectively) (P<0.05). CONCLUSION: Our results indicate that continuous glucose control is necessary to alleviate peripheral nerve damage and that glycemic control during the later period may be more important than early period management. The importance of continuous glucose control, including the later period of diabetes, should therefore be emphasized in diabetic peripheral neuropathy.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetic Neuropathies/prevention & control , Epidermis/innervation , Hyperglycemia/prevention & control , Insulin/administration & dosage , Nerve Fibers, Myelinated/drug effects , Sciatic Nerve/drug effects , Animals , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Neuropathies/physiopathology , Disease Progression , Epidermis/drug effects , Epidermis/metabolism , Epidermis/pathology , Gastric Mucosa/drug effects , Gastric Mucosa/innervation , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Glycated Hemoglobin/analysis , Insulin/therapeutic use , Kidney Cortex/drug effects , Kidney Cortex/innervation , Kidney Cortex/metabolism , Kidney Cortex/pathology , Male , Nerve Fibers, Myelinated/metabolism , Nerve Fibers, Myelinated/pathology , Organ Specificity , Rats , Rats, Sprague-Dawley , Sciatic Nerve/metabolism , Sciatic Nerve/pathology , Severity of Illness Index , Time Factors , Ubiquitin Thiolesterase/metabolismABSTRACT
During normal pregnancy trophoblastic debris is shed from the placenta into the maternal blood and endothelial cells may contribute to the phagocytosis of this material. Many researchers believe the majority of this trophoblastic material is apoptotic in normal pregnancy. Previously we demonstrated that phagocytosis of necrotic, but not apoptotic trophoblastic debris induced endothelial cell activation. In macrophages, phagocytosis of necrotic cell bodies leads to inflammation but phagocytosis of apoptotic bodies actively induces tolerogenic immune responses. We undertook this study to determine whether phagocytosis of apoptotic trophoblastic debris had a "tolerogenic" effect on endothelial cells analogous to their effect in macrophages. Apoptotic or necrotic trophoblastic debris was obtained from placental explants and endothelial cell activation was examined by quantifying, cell surface ICAM-1 expression using ELISAs, or monocyte adhesion. The response of endothelial cells to the activating stimuli of necrotic trophoblastic debris, interleukin-6 (IL-6), Lipopolysaccharide (LPS) or phorbol mysterate acetate (PMA) was reduced in endothelial cells that had phagocytosed apoptotic trophoblastic debris. This protective effect was short-lived being not apparent 24 h after removal of the trophoblastic debris. This work demonstrates that the ability of the endothelial cells to respond to a variety of activating stimuli is reduced by prior phagocytosis of apoptotic trophoblast debris. This might explain why endothelial cells are not activated by the small numbers of necrotic trophoblastic debris that may be found in normal pregnancy. This phenomenon may also contribute to the maternal vascular adaptation that occurs in normal pregnancy.
Subject(s)
Apoptosis , Endothelial Cells/physiology , Phagocytosis/physiology , Trophoblasts/cytology , Cell Line , Endothelial Cells/drug effects , Endothelial Cells/immunology , Female , Humans , Immune Tolerance , Interleukin-6/pharmacology , Lipopolysaccharides/pharmacology , Lung/blood supply , Necrosis , Pregnancy , Tetradecanoylphorbol Acetate/pharmacology , Trophoblasts/immunologyABSTRACT
Steroid 21-hydroxylase deficiency is caused by inactivating mutations in the CYP21A2 gene. This paper reports on the mutation spectrum and the genotype-phenotype correlation of 21-hydroxylase deficiency. 72 unrelated patients with congenital adrenal hyperplasia (CAH) were included. Molecular analysis of CYP21A2 was performed, via the multiplex ligation-dependent probe amplification (MLPA) analysis and sequence-specific differenzial PCR amplification of the CYP21A2 and CYP21A1P genes, using 4 pair-wise sequence-specific primers, followed by sequencing of the entire CYP21A2 gene. Large gene deletions were identified in 45 (31.3%) of the 144 unrelated CAH alleles, whereas the most frequent point mutations were intron 2 splice mutations (c.293-13A>G) (41/144, 28.5%). The MLPA analysis successfully identified 23 of 72 patients (31.9%) with single copy deletion in CYP21A2. This paper describes a rapid and accurate method for the molecular diagnosis of 21-hydroxylase deficiency, which relies on the identification of point mutations and structural rearrangements within the CYP21A2 gene.