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1.
Article in Zh | MEDLINE | ID: mdl-35255587

ABSTRACT

Objective: Using CFD technology to grasp the distribution and diffusion of hydrogen fluoride in an electrolytic fluorine plant, provide guidance and scientific basis for enterprises to carry out occupational health management in enterprises, install hazardous substance alarm devices, and protect workers' occupational health. Methods: In July 2019, the diffusion law of hydrogen fluoride gas produced in an electrolytic fluorine plant is selected as the research object. Through the establishment of models and grids, the Fluent numerical simulation method is finally used to simulate the diffusion and distribution of hydrogen fluoride gas under ventilation conditions. Results: The results showed that the average concentration of hydrogen fluoride was 0.045 mg/m(3) in the workplace, and the absorbed zone height (1.5 m) was 0.02 mg/m(3) in the inspection channel, which was in accordance with the national standard. However, there is eddy current above the electrolyzer near the inlet, may lead to the accumulation of hydrogen fluoride gas. Conclusion: The research of CFD numerical simulation method on the distribution and diffusion of hydrogen fluoride concentration in electrolytic fluorine plant can be applied to the prevention, control and management of occupational hazards in electrolytic fluorine plant.


Subject(s)
Occupational Exposure , Occupational Health , Computer Simulation , Fluorides , Humans , Hydrofluoric Acid , Occupational Exposure/prevention & control
2.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 40(11): 872-875, 2022 Nov 20.
Article in Zh | MEDLINE | ID: mdl-36510727

ABSTRACT

In the process of occupational hazard management, computational fluid dynamics technology can be used to reflect the distribution pattern of occupational hazards in the production process, so as to quickly and accurately guide the formulation of occupational disease prevention and control programs. This paper summarizes and analyzes the current research results on the prevention and control of occupational hazards in workplaces through computational fluid dynamics technology, and describes the application of these research results in the process of occupational disease prevention and control. On this basis, this paper presents the problems and application limitations of existing research and points out the future key research directions, which are of great reference value for guiding further systematic and in-depth research on simulation, experimentation and management of occupational hazards that can cause occupational diseases.


Subject(s)
Hydrodynamics , Occupational Diseases , Humans , Computer Simulation , Safety Management , Technology
3.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(10): 993-999, 2021 Oct 24.
Article in Zh | MEDLINE | ID: mdl-34674437

ABSTRACT

Objective: Explore the usage of anti-hypertension drugs and the rationality of hypertension prescription among the primary health centers in Dongcheng District, Beijing. Method: This cross-sectional and retrospective study was applied to analyze the hypertension prescriptions from the 8 community health centers in Dongcheng District. The anatomical, therapeutic and chemical classification (ATC) codes were used to determine the drug category. ATC information was used to filter data containing antihypertensive drugs, and group the number and proportion of ATC categories. The type of drug was judged by its generic name. According to the diagnosis information in the prescription, the prescription containing the Western medicine diagnosis of hypertension was screened out. The comorbidities of hypertension in the study included 7 types of diseases including diabetes, chronic kidney disease, coronary heart disease, heart failure, atrial fibrillation, stroke, and dyslipidemia. The analysis of prescription rationality included rationality of combination medication, rationality of drug dosage and rationality of drug price. The agreed daily dose (DDD) method was used to analyze the rationality of drug dosage. The drug utilization index (DUI) was used as a quantitative indicator to estimate the rationality of medication, and overdose was expressed by DUI>1. The reasonableness of the drug price was judged based on the price of the drug and whether it was a drug in the "4+7" plan. Results: A total of 658 140 prescriptions were extracted as the final data set, involving 7 categories and 60 commonly used anti-hypertensive drugs, and the corresponding cost of medication was ï¿¥96.58 million. Drugs were prescribed according to comorbidities, and the choice followed the international guidelines. Calcium channel blockers (CCB) were the most prescribed drugs in the prescriptions of patients with comorbidities, and α-adrenergic receptor antagonists were the least prescribed drugs. The proportion of diuretics prescribed in hypertensive patients complicating with heart failure was 21.17% (505/2 385), which was much higher than that of patients complicating with other comorbidities (P<0.05). The proportion of diuretics prescribed in hypertension patients complicating with dyslipidemia was lower than that of patients with other comorbidities (2 639 (0.94%), P<0.05), and ß-blockers (BB) or angiotensin Ⅱreceptor blockers (ARB) were more likely to be selected (BB: 59 348 (21.08%), ARB: 51 356 (18.24%))in these patients. The proportion of BB in prescriptions for hypertension patients with chronic kidney disease was lower than that of patients with other comorbidities (P<0.05). The proportion of BB in prescriptions for hypertension patients with coronary heart disease was higher than that of other comorbidities (P<0.05). Hypertension patients with atrial fibrillation or stroke accounted for a higher proportion of CCB prescriptions (P<0.05). Single antihypertensive drug prescriptions accounted for the highest proportion, 61.19% (402 745/658 140). Two-combination prescriptions accounted for the highest proportion of combination prescriptions, 72.19% (184 392/255 395). CCB based two-combination prescriptions accounted for the highest proportion, 122 350(66.36%). ARB-based tri-combination prescriptions accounted for the highest proportion, 48 915(89.50%),followed by CCB based tri-combination prescriptions (44 732(81.85%)).There were 2 174 (0.33%) prescriptions with unreasonable combination therapies and DUI>1 were found in 48 out of 60 commonly used drugs. In all possible antihypertensive drugs, only 40.92% (109 227/266 993)followed the "4+7" plan. Conclusions: The anti-hypertensive agents from these prescriptions in the primary health centers are diverse, and the choice is generally complied with the guidelines, but some unreasonable situations existed, especially on the combined anti-hypertensive medication, overdose, and"4+7"plan is not followed completely.


Subject(s)
Antihypertensive Agents , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Beijing/epidemiology , Calcium Channel Blockers/therapeutic use , Community Health Centers , Cross-Sectional Studies , Humans , Hypertension/drug therapy , Prescriptions , Retrospective Studies
4.
Zhonghua Gan Zang Bing Za Zhi ; 26(7): 557-560, 2018 Jul 20.
Article in Zh | MEDLINE | ID: mdl-30317784

ABSTRACT

Glucocorticoids is a type of steroid hormone secreted from zona fasciculata of adrenal cortex.As an immune and inflammatory inhibitor, glucocorticoids has been used to treat many kinds of diseases.T cell response plays a crucial role in the pathogenesis of liver diseases. However, the role of glucocorticoids in the mechanism and treatment of liver disease in current clinical practice is controversial. This paper summarizes the progress of glucocorticoid use for the treatment of liver diseases in recent years. References will be provided for how to grasp the indications,application timing and proper dosage of glucocorticoids in liver diseases.


Subject(s)
Adrenal Cortex , Glucocorticoids/therapeutic use , Liver Diseases/drug therapy , Humans , Steroids , Zona Fasciculata/physiology
5.
Gene Ther ; 24(4): 234-240, 2017 04.
Article in English | MEDLINE | ID: mdl-28221337

ABSTRACT

A major challenge in tendon injury is the weak intrinsic healing capacity of tendon that may cause rupture of the repair after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. A total of 128 deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 109 particles of AAV2-VEGF or saline before surgically repaired. At postoperative 4, 6 and 8 weeks, the gliding excursions of tendon were recorded and adhesions around the repair site scored. At 2, 4, 6 and 8 weeks, the ultimate strengths of the healing tendons were tested. Terminal deoxynucleotide transferase dUTP nick end labeling assay were performed to detect cellular apoptosis and immunofluorescence staining to detect type III collagen and matrix metalloprotease-2 (MMP2) expression in tendon tissues. The gliding excursion and adhesion score were similar between AAV2-VEGF-treated tendons and the control tendons. Delivery of AAV2-VEGF significantly increased ultimate strength of the healing tendons at postoperative 4, 6 and 8 weeks (P<0.05). Apoptotic reaction was inhibited from postoperative 2 to 8 weeks in tendon core area or surface area. Type III collagen expression was enhanced at 2, 4, 6 and 8 weeks and MMP2 expression enhanced at 2 and 4 weeks after AAV2-VEGF transfection. The current study confirms the therapeutic efficacy of AAV2-VEGF in improving healing strength of tendon without aggravating adhesion formation after tendon injury, shedding light on the application of molecular therapy in modulating tendon healing.


Subject(s)
Gene Transfer Techniques , Tendon Injuries/therapy , Vascular Endothelial Growth Factor A/therapeutic use , Wound Healing/genetics , Animals , Apoptosis/genetics , Chickens , Dependovirus/genetics , Disease Models, Animal , Tendon Injuries/genetics , Vascular Endothelial Growth Factor A/genetics
6.
Gene Ther ; 23(2): 167-75, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26381218

ABSTRACT

Adhesion formation after digital flexor tendon injury greatly affects gliding function of the tendon, which is a major clinical complication after hand surgery. Transforming growth factor beta 1 (TGF-ß1) has a critical role in adhesion formation during tendon healing. Persistent regulation of TGF-ß1 through application of microRNA (miRNA) specifically inhibiting the function of TGF-ß1 (TGF-ß1-miRNA) holds promise for treatment of such a complication. Adeno-associated virus (AAV) was used to transfer TGF-ß1-miRNA to the chicken digital flexor tendons, which had been injured and surgically repaired. Four doses of AAV2-TGF-ß1-miRNA (2 × 10¹¹, 2 × 10¹°, 2 × 109 and 2 × 108 vector genomes (vg)) were used to determine the transfection efficiency. At postoperative 3 weeks, we found a positive correlation between the administered AAV2-TGF-ß1-miRNA doses and transfection efficiency. The transfection rate ranged from 10% to 77% as the doses increased. Production of TGF-ß1 protein in the tendons decreased on increasing vector dosage. When 2 × 10¹¹ and 2 × 10¹°) vg were injected into the tendon, gliding excursion of the repaired tendon and work of flexion of chicken toes were significantly increased and adhesion score decreased 6 and 8 weeks later, indicating the improvement of tendon gliding and decreases in adhesion formations. However, the ultimate strength of the tendons transfected at the dose of 2 × 10¹° vg was 12-24% lower than that of the control tendons. The results of this study demonstrate that application of TGF-ß1-miRNA had a mixed impact on tendon healing: adhesion around the tendon is reduced but strength of the tendon healing is adversely affected. Future studies should aim at maintaining the beneficial effects of reducing tendon adhesions, while eliminating the adverse effects of decreasing the healing strength.


Subject(s)
Dependovirus/genetics , Genetic Therapy , MicroRNAs/genetics , Tendon Injuries/therapy , Tissue Adhesions/prevention & control , Transforming Growth Factor beta1/therapeutic use , Animals , Chickens , Female , Gene Silencing , Transfection , Transforming Growth Factor beta1/biosynthesis , Transforming Growth Factor beta1/genetics , Wound Healing
7.
J Theor Biol ; 361: 87-100, 2014 Nov 21.
Article in English | MEDLINE | ID: mdl-25017724

ABSTRACT

Wound healing is a complex process in which a sequence of interrelated phases contributes to a reduction in wound size. For diabetic patients, many of these processes are compromised, so that wound healing slows down. In this paper we present a simple ordinary differential equation model for wound healing in which attention focusses on the dominant processes that contribute to closure of a full thickness wound. Asymptotic analysis of the resulting model reveals that normal healing occurs in stages: the initial and rapid elastic recoil of the wound is followed by a longer proliferative phase during which growth in the dermis dominates healing. At longer times, fibroblasts exert contractile forces on the dermal tissue, the resulting tension stimulating further dermal tissue growth and enhancing wound closure. By fitting the model to experimental data we find that the major difference between normal and diabetic healing is a marked reduction in the rate of dermal tissue growth for diabetic patients. The model is used to estimate the breakdown of dermal healing into two processes: tissue growth and contraction, the proportions of which provide information about the quality of the healed wound. We show further that increasing dermal tissue growth in the diabetic wound produces closure times similar to those associated with normal healing and we discuss the clinical implications of this hypothesised treatment.


Subject(s)
Diabetes Mellitus , Models, Biological , Wound Healing , Wounds and Injuries , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetes Mellitus/physiopathology , Humans , Wounds and Injuries/metabolism , Wounds and Injuries/pathology , Wounds and Injuries/physiopathology
8.
J Clin Pharm Ther ; 39(1): 56-60, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24383939

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The many interactions between warfarin and other drugs and foods generate great challenges for clinicians and patients in maintaining stable anitcoagulation. Interactions due to variable vitamin K content of different dietary items influence the therapy of nearly all patients on warfarin. Unfortunately, there is no widely acceptable, patient-friendly strategy for managing such interactions. In this contribution, we propose a practical approach to managing this troublesome interaction, consisting of 'maintaining constant weekly dietary vitamin K intake scores'. METHODS: Twenty-three vitamin K-rich vegetables commonly seen in Taiwanese meals were identified and classified into seven score grades according to their relative vitamin K content per serving. The scores were based on published vitamin K content of different foods. RESULTS AND DISCUSSION: The vitamin K score was equivalent to 5 points for spinach and garland chrysanthemum per bowel, followed by (baby) bok choy, amaranth, arden lettuce (4 points); leaf mustard, edible rape, sweet potato leaf, bai cai and Chinese leek (3 points); and okra and Chinese celery (0·5 points). This classification can be used to guide patients in recording their weekly vitamin K scores with a view to maintaining it when on warfarin. WHAT IS NEW AND CONCLUSION: We suggest a novel approach to patient counselling on warfarin to maintain consistent dietary vitamin K intake and achieve a more stable anticoagulation response. A prospective randomized controlled trial to validate this pragmatic approach would be useful.


Subject(s)
Vitamin K/administration & dosage , Warfarin/administration & dosage , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Blood Coagulation/drug effects , Diet , Food-Drug Interactions , Humans , Male , Taiwan , Vegetables , Vitamin K/adverse effects , Warfarin/adverse effects
9.
West Indian Med J ; 63(1): 94-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-25303182

ABSTRACT

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

11.
Eur Rev Med Pharmacol Sci ; 27(20): 9987-10000, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37916369

ABSTRACT

CFHR5 nephropathy is a type of clinical C3 glomerulopathy, which is a monogenic genetic disease caused by the internal replication of CFHR5 gene, a protein related to the complement regulatory factor H family. The disease seems to be prevalent only in people of Greek Cypriot descent. Because of the special variation of the internal replication of exon 2 and exon 3 of CFHR5 protein in the occurrence of disease, it has had a serious impact on local residents. At present, the mechanism of glomerular damage caused by CFHR5 protein mutations is still unclear. The purpose of this article is to review the clinical research advances of this disease in the past 10 years, including the study of mutant genes, the analysis of mutant proteins and the role of alternative pathways in glomerular injury. It covers the progress in diagnosis and clinical treatment of the disease and looks forward to the future development prospects of its treatment. It is hoped that the recent results will be summarized for the follow-up in-depth study of CFHR5 nephropathy.


Subject(s)
Complement System Proteins , Kidney Diseases , Humans , Complement System Proteins/genetics , Kidney Diseases/genetics , Mutation
12.
J Clin Oncol ; 41(29): 4605-4612, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37797409

ABSTRACT

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA2, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m2 and a 96-hour infusion of fluorouracil 1,000 mg/m2/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P = .003) and 1.96 (P = .007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

13.
Anim Microbiome ; 5(1): 46, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37770990

ABSTRACT

BACKGROUND: The dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiome has been linked to systemic illness, but few studies have evaluated its association with immune-mediated hematological disease. To address this knowledge gap, 16S rRNA gene sequencing was used to profile the fecal microbiota of dogs with spontaneous IMHA and ITP at presentation and following successful treatment. In total, 21 affected and 13 healthy control dogs were included in the study. RESULTS: IMHA/ITP is associated with remodeling of fecal microbiota, marked by decreased relative abundance of the spirochete Treponema spp., increased relative abundance of the pathobionts Clostridium septicum and Escherichia coli, and increased overall microbial diversity. Logistic regression analysis demonstrated that Treponema spp. were associated with decreased risk of IMHA/ITP (odds ratio [OR] 0.24-0.34), while Ruminococcaceae UCG-009 and Christensenellaceae R-7 group were associated with increased risk of disease (OR = 6.84 [95% CI 2-32.74] and 8.36 [95% CI 1.85-71.88] respectively). CONCLUSIONS: This study demonstrates an association of immune-mediated hematological diseases in dogs with fecal dysbiosis, and points to specific bacterial genera as biomarkers of disease. Microbes identified as positive or negative risk factors for IMHA/ITP represent an area for future research as potential targets for new diagnostic assays and/or therapeutic applications.

14.
Zhonghua Yi Xue Za Zhi ; 97(42): 3283-3285, 2017 Nov 14.
Article in Zh | MEDLINE | ID: mdl-29141370
15.
Nat Commun ; 13(1): 447, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35105878

ABSTRACT

Trojan asteroids are small bodies orbiting around the L4 or L5 Lagrangian points of a Sun-planet system. Due to their peculiar orbits, they provide key constraints to the Solar System evolution models. Despite numerous dedicated observational efforts in the last decade, asteroid 2010 TK7 has been the only known Earth Trojan thus far. Here we confirm that the recently discovered 2020 XL5 is the second transient Earth Trojan known. To study its orbit, we used archival data from 2012 to 2019 and observed the object in 2021 from three ground-based observatories. Our study of its orbital stability shows that 2020 XL5 will remain in L4 for at least 4 000 years. With a photometric analysis we estimate its absolute magnitude to be [Formula: see text], and color indices suggestive of a C-complex taxonomy. Assuming an albedo of 0.06 ± 0.03, we obtain a diameter of 1.18 ± 0.08 km, larger than the first known Earth Trojan asteroid.

16.
Cancer ; 117(20): 4740-06, 2011 Oct 15.
Article in English | MEDLINE | ID: mdl-21455999

ABSTRACT

BACKGROUND: On the basis of retrospective experience at individual centers, it appears that patients with stage IV melanoma who undergo complete resection have a favorable outcome compared with patients with disseminated stage IV disease. The Southwest Oncology Group (SWOG) performed a prospective trial in patients with metastatic melanoma who were enrolled before complete resection of their metastatic disease and provided prospective outcomes in the cooperative group setting. METHODS: Based on their physical examination and radiologic imaging studies, patients with a stage IV melanoma judged amenable to complete resection underwent surgery within 28 days of enrollment. All eligible patients were followed with scans (computed tomography or positron emission tomography) every 6 months until relapse and death. RESULTS: Seventy-seven patients were enrolled from 18 different centers. Of those, 5 patients were ineligible; 2 had stage III disease alone; and 3 had no melanoma in their surgical specimen. In addition, 8 eligible patients had incompletely resected tumor. Therefore, the primary analysis included 64 completely resected patients. Twenty patients (31%) had visceral disease. With a median follow-up of 5 years, the median relapse-free survival was 5 months (95% CI, 3-7 months) whereas median overall survival was 21 months (95% CI, 16-34 months). Overall survivals at 3 and 4 years were 36% and 31%, respectively. CONCLUSIONS: In a prospective multicenter setting, appropriately selected patients with stage IV melanoma achieved prolonged overall survival after complete surgical resection. Although median relapse-free survival was only 5 months, patients could still frequently undergo subsequent surgery for isolated recurrences. This patient population is appropriate for aggressive surgical therapy and for trials evaluating adjuvant therapy.


Subject(s)
Melanoma/pathology , Melanoma/surgery , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Adult , Aged , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Patient Selection , Positron-Emission Tomography , Prognosis , Prospective Studies , Tomography, X-Ray Computed , Treatment Outcome , United States
17.
Eur Respir J ; 38(4): 841-50, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21565918

ABSTRACT

Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses. Wildtype (WT) mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1(+/-) and ROCK2(+/-), respectively) were sensitised and challenged with ovalbumin. ROCK expression and activation were assessed by western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment. Compared with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1(+/-) and ROCK2(+/-) mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1(+/-) and ROCK2(+/-) lungs. Airway responsiveness was comparable in WT, ROCK1(+/-), and ROCK2(+/-) mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1(+/-) or ROCK2(+/-) mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1(+/-) and ROCK2(+/-) versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses.


Subject(s)
Bronchial Hyperreactivity/immunology , Hypersensitivity/immunology , rho-Associated Kinases/immunology , Animals , Bronchial Hyperreactivity/genetics , Bronchial Hyperreactivity/pathology , Bronchoalveolar Lavage Fluid/immunology , Cells, Cultured , Coculture Techniques , Dendritic Cells/cytology , Dendritic Cells/immunology , Eosinophils/immunology , Eosinophils/pathology , Female , Gene Expression/immunology , Goblet Cells/immunology , Goblet Cells/pathology , Hypersensitivity/genetics , Hypersensitivity/pathology , Interleukin-13/immunology , Interleukin-5/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Pneumonia/genetics , Pneumonia/immunology , Pneumonia/pathology , Respiratory Mechanics/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , rho-Associated Kinases/genetics
19.
Am J Physiol Heart Circ Physiol ; 298(6): H2154-63, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20382965

ABSTRACT

We have recently demonstrated that the inhibition of histone deacetylases (HDAC) protects the heart against ischemia-reperfusion (I/R) injury. The mechanism by which HDAC inhibition confers myocardial protection remains unknown. The purpose of this study is to investigate whether the disruption of NF-kappaB p50 would eliminate the protective effects of HDAC inhibition. Wild-type and NF-kappaB p50-deficient mice were treated with trichostatin A (TSA; 0.1 mg/kg ip), a potent inhibitor of HDACs. Twenty-four hours later, the hearts were perfused in Langendorff model and subjected to 30 min of ischemia and 30 min of reperfusion. Inhibition of HDACs by TSA in wild-type mice produced marked improvements in left ventricular end-diastolic pressure, left ventricular rate pressure product, and the reduction of infarct size compared with non-TSA-treated group. TSA-induced cardioprotection in wild-type animals was absent with genetic deletion of NF-kappaB p50 subunit. Notably, Western blot displayed a significant increase in nuclear NF-kappaB p50 and the immunoprecipitation demonstrated a remarkable acetylation of NF-kappaB p50 at lysine residues following HDAC inhibition. EMSA exhibited a subsequent increase in NF-kappaB DNA binding activity. Luciferase assay demonstrated an activation of NF-kappaB by HDAC inhibition. The pretreatment of H9c2 cardiomyoblasts with TSA (50 nmol/l) decreased cell necrosis and increased in cell viability in simulated ischemia. The resistance of H9c2 cardiomyoblasts to simulated ischemia by HDAC inhibition was eliminated by genetic knockdown of NF-kappaB p50 with transfection of NF-kappaB p50 short interfering RNA but not scrambled short interfering RNA. These results suggest that NF-kappaB p50 acetylation and activation play a pivotal role in HDAC inhibition-induced cardioprotection.


Subject(s)
Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/drug effects , Histone Deacetylases/metabolism , Hydroxamic Acids/pharmacology , Myocardial Reperfusion Injury/prevention & control , NF-kappa B p50 Subunit/genetics , NF-kappa B p50 Subunit/metabolism , Acetylation , Animals , Cells, Cultured , DNA/metabolism , Disease Models, Animal , Male , Mice , Mice, Knockout , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , NF-kappa B p50 Subunit/drug effects , Necrosis/prevention & control , RNA, Small Interfering/pharmacology , Ventricular Function, Left/physiology
20.
Int J Androl ; 33(4): 581-7, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-19622086

ABSTRACT

XXY mouse has been characterized as an experimental model for men with Klinefelter's syndrome (XXY male phenotype). To test whether donor XY germ cells could proliferate and differentiate in the XXY testicular environment, donor testicular cells from adult (2-3 months old) and immature (10 days old) XY green fluorescence protein (GFP) transgenic mice were transplanted into the seminiferous tubules of adult (4-7 months old) and young (6 weeks old) XXY recipient mice respectively. Twelve weeks after transplantation, GFP positive spermatogonia were found in 21.74% (five out of 23) of adult XXY recipients who received adult donor cells. The GFP positive segments of seminiferous tubules were observed in 44.44% (four out of nine) young XXY recipients who received donor cells from 10 days old GFP mice. We found using immunohistochemistry and cell morphology that donor-derived GFP positive germ cells were spermatogonia, spermatocytes, round spermatids and spermatozoa in some of the seminiferous tubules of young XXY recipient mice. The results demonstrated that the donor XY germ cells were able to qualitatively complete spermatogenesis in some of the seminiferous tubules of XXY mice.


Subject(s)
Germ Cells/transplantation , Klinefelter Syndrome/genetics , Testis/cytology , Animals , Cell Differentiation , Cell Proliferation , Green Fluorescent Proteins/genetics , Male , Mice , Mice, Transgenic , Spermatozoa/cytology
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