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1.
Clin Exp Dermatol ; 43(7): 798-805, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29740850

ABSTRACT

BACKGROUND: Artemisia scoparia Waldst. et Kitaib (AS) (Oriental wormwood, known as Bissuk in Korea) is a plant used in cosmetic and pharmaceutical treatments. However, the effect of AS on atopic dermatitis (AD) has not been described. AIM: To examine the inhibitory effect of AS on AD using a murine model. METHODS: We applied either AS, the butanol-extracted fraction of AS (Bu-OH) or 3,5-dicaffeoyl-epi-quinic acid (DEQA, a major component of Bu-OH) topically for 3 weeks to 2,4-dinitrofluorobenzene (DNFB)-induced skin lesions in BALB/c mice. RESULTS: AS, Bu-OH and DEQA suppressed the clinical symptoms of DNFB-induced skin lesions and he associated scratching behaviour. Numbers of inflammatory cells infiltrating skin lesions were significantly reduced by AS or Bu-OH application but not by DEQA. In addition, AS significantly suppressed serum levels of histamine and IgE, while Bu-OH significantly suppressed serum levels of histamine, IgE, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4 and IL-6, and DEQA significantly suppressed serum levels of histamine, IgE, TSLP and IL-4 in DNFB-induced AD mice. In skin lesions, AS and Bu-OH significantly reduced inflammatory cytokines, whereas DEQA did not. AS, Bu-OH and DEQA all significantly suppressed caspase-1 activities. CONCLUSIONS: These results demonstrate the anti-AD effects of AS, Bu-OH and DEQA, and suggest that all three have therapeutic potential.


Subject(s)
Artemisia , Caspase 1/metabolism , Chlorogenic Acid/analogs & derivatives , Dermatitis, Atopic/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Administration, Topical , Animals , Caspase 1/genetics , Chlorogenic Acid/therapeutic use , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Dinitrofluorobenzene , Disease Models, Animal , Medicine, Korean Traditional , Mice , Mice, Inbred BALB C , RNA, Messenger/metabolism , Skin/pathology
2.
Transplant Proc ; 50(4): 1005-1008, 2018 May.
Article in English | MEDLINE | ID: mdl-29731056

ABSTRACT

BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival. RESULTS: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization. CONCLUSION: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival.


Subject(s)
Graft Rejection/immunology , Graft Survival/immunology , Kidney Transplantation/adverse effects , Macrophages/immunology , Adult , Female , Graft Rejection/pathology , Humans , Kaplan-Meier Estimate , Kidney Transplantation/methods , Kidney Transplantation/mortality , Macrophages/pathology , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Transplantation, Homologous
3.
Clin Exp Allergy ; 48(7): 875-889, 2018 07.
Article in English | MEDLINE | ID: mdl-29752758

ABSTRACT

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.


Subject(s)
Cytokines/adverse effects , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism , Rhinitis, Allergic/etiology , Rhinitis, Allergic/metabolism , Anaphylaxis , Animals , Cell Degranulation/immunology , Cell Differentiation/immunology , Cell Line , Cytokines/metabolism , Disease Models, Animal , Humans , Mast Cells/immunology , Mast Cells/metabolism , Mast Cells/ultrastructure , Mice , Mice, Knockout , Ovalbumin/adverse effects , STAT6 Transcription Factor/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Thymic Stromal Lymphopoietin
4.
Lupus ; 27(8): 1338-1347, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29688144

ABSTRACT

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01-1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03-2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24-0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85-1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03-9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12-28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.


Subject(s)
Autoantibodies/blood , Lupus Vasculitis, Central Nervous System/immunology , Lupus Vasculitis, Central Nervous System/mortality , Adolescent , Adult , Female , Humans , Logistic Models , Male , Multivariate Analysis , Prevalence , Prospective Studies , Risk Factors , Severity of Illness Index , Young Adult
5.
AJNR Am J Neuroradiol ; 39(5): 864-868, 2018 05.
Article in English | MEDLINE | ID: mdl-29519788

ABSTRACT

BACKGROUND AND PURPOSE: During stent-assisted coiling of ICA aneurysms, stent tips are sometimes unintentionally embedded into ICA branches. Stent tips can be visualized because they have radiopaque markers. Concerns regarding stent tip misplacement include risks of artery perforation and occlusion. The aim of this study was to evaluate the long-term outcomes of ICA branches with embedded stent tips. MATERIALS AND METHODS: ICA branches with embedded stent tips were identified among 35 patients with unruptured ICA aneurysms treated with stent-assisted coiling between November 2003 and November 2014. Patient clinical and angiographic outcomes associated with the embedded stent tip were analyzed. RESULTS: Most of the 35 studied aneurysms were paraclinoid ICA aneurysms (n = 30). The most commonly involved ICA branch was the posterior communicating artery (26 patients, 74.3%), followed by the anterior choroidal artery (8 patients, 22.9%) and ophthalmic artery (1 patient, 2.9%). During the follow-up period (38.6 ± 17.9 months), no new neurologic deficits developed. Neither hemorrhagic nor thromboembolic events occurred. Angiography was performed during the final follow-up evaluation at a mean of 32.7 ± 18.0 months, and all ICA branches with embedded stent tips showed patent blood flow without severe luminal narrowing. CONCLUSIONS: In our experience, placement of a stent tip into ICA branches during stent-assisted coiling was not associated with any major adverse events.


Subject(s)
Carotid Artery, Internal/pathology , Embolization, Therapeutic/adverse effects , Endovascular Procedures/adverse effects , Intracranial Aneurysm/therapy , Stents/adverse effects , Adult , Aged , Embolization, Therapeutic/instrumentation , Endovascular Procedures/instrumentation , Female , Humans , Male , Middle Aged , Treatment Outcome
6.
Transplant Proc ; 48(8): 2656-2662, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27788797

ABSTRACT

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.


Subject(s)
Biopsy , Kidney Transplantation , Kidney/pathology , Transplants/pathology , Adult , Aged , Female , Graft Survival , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Tissue Donors , Treatment Outcome
7.
Transplant Proc ; 48(3): 887-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234759

ABSTRACT

BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution. RESULTS: Sixteen patients (14.4%) had PTDM at the time of diagnosis of PTIgAN, which increased to 28 patients (25.2%) at the last follow-up (10.4 years after transplantation). Donor ages were younger in PTIgAN patients with concurrent PTDM. However, other clinical and demographic data were not significantly different between PTIgAN patients with and without PTDM. Histologically, Banff "mm" scores were higher and "M1" of the Oxford classification was more frequent in PTIgAN patients with concurrent PTDM than in patients without PTDM, but the difference did not reach statistical significance. Serum creatinine levels and proteinuria at the time of biopsy and overall graft survival did not vary according to the presence of PTDM both at biopsy and at the last follow-up. CONCLUSIONS: Concurrent PTDM does not significantly influence graft function or outcome for 10 years after transplantation in PTIgAN patients.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/etiology , Forecasting , Glomerulonephritis, IGA/surgery , Kidney Transplantation/adverse effects , Postoperative Complications , Adult , Biopsy , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Female , Follow-Up Studies , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/epidemiology , Graft Survival , Humans , Incidence , Kidney/ultrastructure , Male , Microscopy, Electron , Prevalence , Republic of Korea/epidemiology , Retrospective Studies , Transplantation, Homologous
8.
Orthop Traumatol Surg Res ; 102(2): 257-60, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26969206

ABSTRACT

UNLABELLED: Sciatica can occur due to a spinal lesion, intrapelvic tumor, diabetic neuropathy, and rarely piriformis syndrome. The causes of piriformis syndrome vary by a space-occupying lesion. A ganglionic cyst can occur in various lesions in the body but seldom around the hip joint. In addition, sciatica due to a ganglionic cyst around the hip joint has been reported in one patient in Korea who underwent surgical treatment. We experienced two cases of sciatica from a piriformis ganglionic cyst and we report the clinical characterics and progress after non-operative treatment by ultrasonography-guided aspiration. The two cases were diagnosed by magnetic resonance imaging and were treated by ultrasonography-guided aspiration. We followed the patients for more than 6months. The symptoms of piriformis syndrome from the ganglion improved following aspiration and this conservative treatment is a treatment method that can be used without extensive incision or cyst excision. LEVEL OF EVIDENCE: Level IV historical case.


Subject(s)
Ganglion Cysts/complications , Piriformis Muscle Syndrome/etiology , Sciatica/etiology , Adult , Female , Ganglion Cysts/diagnosis , Humans , Magnetic Resonance Imaging , Male
9.
Transplant Proc ; 47(3): 622-5, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25891698

ABSTRACT

The term "isolated v-lesion" was proposed at the 2009 Banff conference on allograft pathology. It is still debated whether the isolated v-lesion is a part of the antibody-mediated or T cell-mediated rejection and whether the isolated v-lesion has any prognostic significance of its own. To investigate the characteristics of the isolated v-lesion, we identified infiltrating inflammatory cells in renal allograft biopsy specimens with these lesions. We selected 11 allograft renal biopsy specimens which were compatible with the original definition of the isolated v-lesion (v1 or v2 with i ≤ 1 and t ≤ 1) and had enough paraffin-embedded tissue for immunohistochemistry. We performed immunohistochemistry for markers of T cells (CD3, CD4, and CD8), B cells (CD20), NK/T cells (CD56), and macrophages (CD68). The number of positive cells was counted in each compartment of the renal tissue including the arteries, peritubular capillaries, glomeruli, tubules, and interstitium. Arteries were infiltrated by CD3/CD8-positive T cells and CD68-positive macrophages. Three cases showed T cell-dominant infiltrates and four cases showed macrophage-dominant infiltrates. Glomeruli showed a similar inflammatory cell profile to that of arteries. Tubulitis was composed of CD3/CD8-positive T cells. The components of interstitial inflammation were more variable with the presence of CD20-positive B cells. In six cases, interstitial infiltrates were predominantly composed of CD3/CD8-positive T cells, and two of these cases showed almost exclusive infiltrates of T cells. However, four cases showed co-dominant infiltrates of T and B cells, and one case showed predominant B cell infiltrates. The isolated v-lesion has a heterogeneous pathogenesis, and B cell-predominant infiltrates in some cases suggest that this lesion could be related to an antibody-related process.


Subject(s)
Allografts/immunology , Graft Rejection/immunology , Kidney Transplantation , Kidney/immunology , Lymphocytes/metabolism , Macrophages/metabolism , Adult , Aged , Allografts/pathology , Biomarkers/metabolism , Biopsy , Female , Graft Rejection/pathology , Humans , Immunohistochemistry , Kidney/pathology , Male , Middle Aged , Transplantation, Homologous
10.
Enzyme Microb Technol ; 67: 59-66, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25442950

ABSTRACT

This study aimed to develop viable enzymes for bioconversion of resveratrol-glucoside into resveratrol. Out of 13 bacterial strains tested, Lactobacillus kimchi JB301 could completely convert polydatin into resveratrol. The purified enzyme had an optimum temperature of 30-40°C and optimum pH of pH 5.0 against polydatin. This enzyme showed high substrate specificities towards different substrates in the following order: isorhaponticin>>polydatin>>mulberroside A>oxyresveratrol-3-O-glucoside. Additionally, it rarely hydrolyzed astringin and desoxyrhaponticin. Based on these catalytic specificities, we suggest this enzyme be named stilbene glucoside-specific ß-glucosidase. Furthermore, polydatin extracts from Polygonum cuspidatum were successfully converted to resveratrol with a high yield (of over 99%). Stilbene glucoside-specific ß-glucosidase is the first enzyme isolated from lactic acid bacteria capable of bio-converting various stilbene glucosides into stilbene.


Subject(s)
Bacterial Proteins/isolation & purification , Bacterial Proteins/metabolism , Glucosides/metabolism , Lactobacillus/enzymology , Stilbenes/metabolism , beta-Glucosidase/isolation & purification , beta-Glucosidase/metabolism , Biotransformation , Disaccharides/metabolism , Industrial Microbiology , Lactobacillus/genetics , Resveratrol , Substrate Specificity
11.
Asian-Australas J Anim Sci ; 27(4): 537-42, 2014 Apr.
Article in English | MEDLINE | ID: mdl-25049985

ABSTRACT

This study was carried out to optimize cholesterol removal in whole egg using crosslinked ß-cyclodextrin (ß-CD) and to recycle the ß-CD. Various factors for optimizing conditions were concentration of the ß-CD, mixing temperature, mixing time, mixing speed and centrifugal speed. In the result of this study, the optimum conditions of cholesterol removal were 25% crosslinked ß-CD, 40°C mixing temperature, 30 min mixing time, 1,200 rpm mixing speed and 2,810×g centrifugal speed. The recycling was repeated five times. The cholesterol removal was 92.76% when treated with the optimum conditions. After determining the optimum conditions, the recyclable yields of the crosslinked ß-CD ranged from 86.66% to 87.60% in the recycling and the percentage of cholesterol removal was over 80% until third recycling. However, the cholesterol removal efficiency was decreased when the number of repeated recycling was increased. Based on the result of this study, it was concluded that the crosslinked ß-CD was efficient for cholesterol removal in whole egg, and recycling is possible for only limited repeating times due to the interaction of the ß-CD and egg protein.

12.
Transplant Proc ; 45(8): 2937-40, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24157007

ABSTRACT

BACKGROUND: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function. METHODS: Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria. RESULTS: Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001). CONCLUSION: A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation.


Subject(s)
Graft Survival , Kidney Transplantation , Living Donors , Biopsy , Female , Glomerular Filtration Rate , Humans , Kidney/pathology , Male , Retrospective Studies
13.
Neuroscience ; 253: 389-97, 2013 Dec 03.
Article in English | MEDLINE | ID: mdl-24036377

ABSTRACT

We have previously shown that chloride ion flux plays an important role in receptor tyrosine kinase A (TrkA)-mediated signaling pathway during nerve growth factor (NGF)-induced differentiation in pheochromocytoma (PC12) cells. Here we found out that chloride channel 4 (CLC-4) is responsible for the NGF-induced neurite outgrowth in neuronal cells. Using a patch-clamp technique, we found that NGF treatment increased anionic conductance in PC12 cells, an effect which was blocked by transfection of siRNA of CLC-4. Also, the NGF-induced TrkA phosphorylation and subsequent Akt/moesin phosphorylation was suppressed in the CLC-4 knock down cells. Moreover, CLC-4 knock down also suppressed the neurite outgrowth in response to long-term treatment of NGF in PC12 cells and in primary cortical neurons. In summary, our results suggest that CLC-4 is an important mediator of the TrkA-mediated signaling pathway and thus, the NGF-induced differentiation of neuronal cells.


Subject(s)
Cerebral Cortex/cytology , Chloride Channels/metabolism , Nerve Growth Factor/pharmacology , Neurites/drug effects , Neurons/cytology , Signal Transduction/drug effects , Animals , Cells, Cultured , Chloride Channels/genetics , Dose-Response Relationship, Drug , Drug Interactions , Embryo, Mammalian , Enzyme Inhibitors/pharmacology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neurites/physiology , PC12 Cells , Potassium Channel Blockers/pharmacology , Rats , Receptor, trkA/metabolism , Signal Transduction/physiology , Tetraethylammonium/pharmacology , Time Factors
14.
Br J Pharmacol ; 170(2): 245-54, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23713957

ABSTRACT

BACKGROUND AND PURPOSE: Antagonists of the N-type voltage gated calcium channel (VGCC), Cav 2.2, have a potentially important role in the treatment of chronic neuropathic pain. ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. CVID is reported to have a greater therapeutic index than MVIIA in neuropathic pain models, and it has been suggested that this is due to faster reversibility of binding, but it is not known whether this can be improved further. EXPERIMENTAL APPROACH: We examined the potency of CVID, MVIIA and two intermediate hybrids ([K10R]CVID and [R10K]MVIIA) to reverse signs of neuropathic pain in a rat nerve ligation model in parallel with production of side effects. We also examined the potency and reversibility to inhibit primary afferent synaptic neurotransmission in rat spinal cord slices. KEY RESULTS: All ω-conotoxins produced dose-dependent reduction in mechanical allodynia. They also produced side effects on the rotarod test and in a visual side-effect score. CVID displayed a marginally better therapeutic index than MVIIA. The hybrids had a lesser effect in the rotarod test than either of their parent peptides. Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed recovery that was largely dependent upon the magnitude of inhibition and not the conotoxin type. CONCLUSIONS AND IMPLICATIONS: These findings indicate that CVID provides only a marginal improvement over MVIIA in a preclinical model of neuropathic pain, which appears to be unrelated to reversibility from binding. Hybrids of these conotoxins might provide viable alternative treatments.


Subject(s)
Analgesics, Non-Narcotic/pharmacology , Neuralgia/drug therapy , omega-Conotoxins/pharmacology , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/toxicity , Animals , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Hyperalgesia/drug therapy , Male , Neuralgia/physiopathology , Peptides/administration & dosage , Peptides/chemistry , Peptides/pharmacology , Rats , Rats, Sprague-Dawley , Rotarod Performance Test , Spinal Cord/drug effects , Spinal Cord/metabolism , Synaptic Transmission/drug effects , omega-Conotoxins/administration & dosage , omega-Conotoxins/toxicity
15.
Lymphology ; 46(4): 160-72, 2013 Dec.
Article in English | MEDLINE | ID: mdl-25141459

ABSTRACT

The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis.


Subject(s)
Hyaluronoglucosaminidase/administration & dosage , Lymphangiogenesis/drug effects , Lymphatic Vessels/drug effects , Lymphedema/drug therapy , Acute Disease , Animals , Disease Models, Animal , Female , Gene Expression , Glycoproteins/agonists , Glycoproteins/genetics , Glycoproteins/metabolism , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Injections, Intralesional , Lymphangiogenesis/genetics , Lymphatic Vessels/metabolism , Lymphatic Vessels/pathology , Lymphedema/genetics , Lymphedema/metabolism , Lymphedema/pathology , Membrane Glycoproteins/agonists , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Transport Proteins , Mice , Neutrophils/drug effects , Neutrophils/pathology , Tail , Transforming Growth Factor beta1/antagonists & inhibitors , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor Receptor-3/agonists , Vascular Endothelial Growth Factor Receptor-3/genetics , Vascular Endothelial Growth Factor Receptor-3/metabolism
16.
Transplant Proc ; 44(3): 616-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22483451

ABSTRACT

Transplant glomerulopathy (TG) a morphological feature of chronic active antibody-mediated rejection, is associated with donor-specific antibody, peritubular capillary deposition of C4d, and multilayering of peritubular capillary basement membranes. To evaluate the significance of accompanying nonimmunologic injuries in TG, we retrospectively reviewed 2839 renal allograft cases at our institute among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples showed accompanying diseases such as chronic calcineurin inhibitor toxicity, hepatitis viral infection, posttransplant diabetes, and glomerulonephritis. Comparing the pure form of TG with TG-mixed diseases, there was no difference in patient demography, serum creatinine values, and proteinuria. Among histological parameters, severe hyalinosis was more frequently observed among the TG plus other diseases group. The two groups did not show significant difference in graft survival (P = .216).


Subject(s)
Glomerulonephritis/etiology , Graft Survival , Kidney Transplantation/adverse effects , Glomerulonephritis/physiopathology , Humans , Retrospective Studies
17.
Transplant Proc ; 44(3): 619-20, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22483452

ABSTRACT

Membranous nephropathy (MN) may develop as recurrence or de novo after transplantation. Recently, autoimmune or alloimmune responses to unspecified glomerular antigens have been considered as a pathogenetic mechanism. To explore the relationship between antibody-mediated injury and posttransplantation MN, we tested C4d positivity using polyclonal antibody in renal allograft biopsy samples diagnosed as posttransplantation MN. A total of 19 cases (16 males and 3 females), including 2 recurrent and 7 de novo forms, were the subject of the study. On light microscopy, stage II was the most common (n = 9). In addition to glomerular capillary immunoglobulin (Ig)G deposits, all but 2 cases having only sclerotic glomeruli were C4d-positive in glomerular capillary walls. Twelve cases were also positive in cortical peritubular capillaries (PTCs): diffuse in 8 cases and focal in 4 cases. Two of 3 cases associated with acute rejection and 3 of 4 cases associated with chronic rejection were PTC C4d-positive. The frequency of C4d positivity in PTCs was significantly higher than that of posttransplantation IgA nephropathy (P = .028). In conclusion, a higher frequency of PTC C4d positivity suggests an involvement of chronic antibody-mediated injury in the evolution of posttransplantation MN.


Subject(s)
Autoantibodies/immunology , Basement Membrane/metabolism , Complement C4b/metabolism , Glomerulonephritis, Membranous/immunology , Kidney Transplantation/immunology , Peptide Fragments/metabolism , Adult , Female , Humans , Immunohistochemistry , Male
18.
Acta Anaesthesiol Scand ; 56(6): 770-6, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22288930

ABSTRACT

BACKGROUND: Dose requirements of thiopental depend on patient characteristics and infusion rate. We determined thiopental dose requirements for induction of anaesthesia, and the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation in spinal cord-injured (SCI) patients undergoing general anaesthesia. METHODS: Twenty patients with traumatic complete SCI undergoing elective surgery were enrolled. Twenty patients without SCI served as control. Anaesthesia was induced with thiopental, followed by remifentanil 1 µg/kg and rocuronium 0.8 mg/kg, and maintained with 2% sevoflurane and 50% nitrous oxide in oxygen after tracheal intubation. Thiopental was administered at a rate of 50 mg/15 s until abolition of the eyelash reflex. Thiopental doses, BIS values, systolic arterial blood pressure (SAP), heart rate (HR) and plasma catecholamine concentrations were measured. RESULTS: Total thiopental dose required to abolish the eyelash reflex based on total body weight (BW) (5.26 ± 0.87 vs. 3.91 ± 1.07 mg/kg, P < 0.001) or lean BW (6.56 ± 1.37 vs. 5.24 ± 1.36 mg/kg, P < 0.01) were significantly smaller in the SCI group than in the control. SAP was decreased by induction of anaesthesia with thiopental and remifentanil, and increased by tracheal intubation in both groups. However, the peak SAP after intubation was smaller in the SCI patients. HR increased significantly above baseline values following intubation in both groups with no significant intergroup differences. Hypertension was more frequent in the control group. Norepinephrine concentrations remained unaltered following intubation in both groups. CONCLUSIONS: These results suggest that the dose requirements of thiopental for induction of general anaesthesia and subsequent tracheal intubation are reduced in the SCI patients.


Subject(s)
Anesthesia, Intravenous , Anesthetics, Intravenous/administration & dosage , Intubation, Intratracheal/methods , Spinal Cord Injuries/complications , Thiopental/administration & dosage , Adult , Anesthesia, General , Anesthetics, Inhalation , Arousal/physiology , Blood Pressure/physiology , Catecholamines/blood , Consciousness Monitors , Dose-Response Relationship, Drug , Female , Heart Rate/physiology , Humans , Male , Methyl Ethers , Monitoring, Intraoperative , Nitrous Oxide , Oxygen/blood , ROC Curve , Reflex/drug effects , Sample Size , Sevoflurane
19.
Amino Acids ; 42(5): 1609-18, 2012 May.
Article in English | MEDLINE | ID: mdl-21344174

ABSTRACT

The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1ß, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.


Subject(s)
Anti-Allergic Agents/administration & dosage , Glutamates/administration & dosage , Mast Cells/drug effects , Plant Extracts/administration & dosage , Tea , Anaphylaxis/drug therapy , Animals , Cell Line , Gene Expression Regulation/drug effects , Histamine/metabolism , Humans , Hypersensitivity/drug therapy , Hypersensitivity/mortality , Immunoglobulin E/metabolism , Male , Mast Cells/cytology , Mice , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Tetradecanoylphorbol Acetate/analogs & derivatives , Tumor Necrosis Factor-alpha/metabolism , p-Methoxy-N-methylphenethylamine/administration & dosage
20.
Biotechnol Lett ; 34(3): 515-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22072113

ABSTRACT

Alliinase (alkylsulphenate lyase, EC 4.4.1.4), which catalyses the production of allicin, was immobilized in alginate microparticles. Addition of pyridoxal 5'-phosphate to the microparticles enhanced alliinase activity. Encapsulated alliinase were significantly higher (30 and 22%, respectively) than those of non-encapsulated alliinase at 60°C and at pH 2. Therefore, microencapsulation of alliinase with alginate can offer an effective way of sustaining enzyme activity during oral administration and passage through the stomach.


Subject(s)
Alginates/chemistry , Capsules/chemistry , Carbon-Sulfur Lyases/metabolism , Enzymes, Immobilized/metabolism , Carbon-Sulfur Lyases/chemistry , Disulfides , Enzyme Activators/metabolism , Enzyme Stability , Enzymes, Immobilized/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Hydrogen-Ion Concentration , Pyridoxal/analogs & derivatives , Pyridoxal/metabolism , Sulfinic Acids/metabolism , Temperature
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