Abstract 419: Human ApoB100/CETP Transgenic Mouse is a Useful Animal Model for Evaluation of HDL-C Elevation and Suppression of Atherosclerosis by Peroxisome Proliferator-Activated Receptor Delta Agonist

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Noriyuki Naya ◽  
Keita Fukao ◽  
Akemi Nakamura ◽  
Kohji Nomura ◽  
Seijiro Hara ◽  
...  
Keyword(s):  
Term Treatment ◽  
Serum Lipoprotein ◽  
Peroxisome Proliferator ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Class ◽  
Promising Target ◽  
Long Term Treatment ◽  
Apoe Ko Mice ◽  
Lipoprotein Profiles

PPARδ is one of the transcription factors that regulate lipid metabolism. Recently, PPARδ agonists have been reported to induce the elevation of plasma HDL-C levels in obese mice, rhesus monkeys as well as humans, indicating their potentials as a new class of HDL-C raising agent. In addition, anti-atherosclerotic effects of PPARδ agonists were reported in LDLR-KO and ApoE-KO mice. In these mice, however, the lipoprotein profiles are greatly different from those in humans in terms of the deficiency in CETP and ApoB100, and thus the anti-inflammatory effects were regarded as a main anti-atherosclerotic mechanism of PPARδ agonists. It has been reported that human ApoB100/CETP transgenic (hApoB100/CETP-Tg) mice have similar lipoprotein profiles with humans. In this study, we used hApoB100/CETP-Tg mice placed under a western diet for evaluation of GW501516, one of the most potent and selective PPARδ agonists, in order to investigate the linkage between HDL-C elevation and anti-atherosclerotic potency. For evaluation of plasma HDL-C levels, the hApoB100/CETP-Tg mice were orally treated with GW501516 for 1 week and its potency was compared with fenofibrate, a PPARα agonist used in the clinic. For evaluation of the anti-atherosclerotic effect, the mice were orally treated with GW501516 for 18 weeks and atherosclerosis at the aortic valves was determined by cross-sectional lesion analysis. Serum lipoprotein parameters were periodically monitored and lipoprotein profiles were analyzed by FPLC method. Treatment with GW501516 resulted in significant elevation of plasma HDL-C levels with more potency compared to fenofibrate (24% and 15% elevation at 10mg/kg, respectively). Serum apoA-I was also increased by the similar ratio as HDL-C, and the particle size of HDL was not changed, suggesting that the numbers of HDL particle are increased by GW501516. Long term treatment of GW501516 (3 and 10 mg/kg) resulted in dose-dependent suppression of atherosclerosis (42 and 57% inhibition, respectively) with a strong correlation with HDL-C elevation (p<0.001). By using hApoB100/CETP-Tg mice, PPARδ was confirmed as a promising target of anti-atherosclerotic therapy as a new class of HDL-C raising agent.

scholarly journals Concomitant use of rapamycin and rosiglitazone delays the progression of polycystic kidney disease in Han:SPRD rats: a study of the mechanism of action

2018 ◽  
Vol 314 (5) ◽  
pp. F844-F854 ◽  
Author(s):  
Chunyan Liu ◽  
Hongdong Li ◽  
Xiang Gao ◽  
Ming Yang ◽  
Li Yuan ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Mammalian Target Of Rapamycin ◽  
Term Treatment ◽  
Peroxisome Proliferator ◽  
Polycystic Kidney ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Long Term Treatment

Attributing to their antiproliferative effect, both rapamycin and peroxisome proliferator-activated receptor-γ (PPARγ) can halt the progression of autosomal dominant polycystic kidney disease (ADPKD). Whether combined use could enhance this effect is unknown. The present study used rapamycin and the PPARγ agonist rosiglitazone concomitantly to observe their combined effects on the proliferation of ADPKD cyst-lining epithelial cells and the progression of ADPKD in Han:SPRD rats. Concomitant use of the two drugs inhibited the proliferation of WT9–12 cells significantly through a superimposition effect. Rosiglitazone inhibited the phosphorylation of mammalian target of rapamycin p70S6K. Concomitant use of rosiglitazone and rapamycin further downregulated the p-p70S6K level. Rosiglitazone also inhibited the phosphorylation of Akt and antagonized the activation of Akt induced by rapamycin. Concomitant use of rosiglitazone and rapamycin significantly retarded the deterioration of renal function, decreased cyst cell proliferation and interstitial fibrosis in Han:SPRD rats. Rapamycin significantly increased cholesterol levels in the blood, whereas rosiglitazone mitigated rapamycin-induced hyperlipidemia. These results indicate that the effects of concomitant use of rosiglitazone and rapamycin in inhibiting the proliferation of WT9–12 cells and delaying the progression of ADPKD in Han:SPRD rats are stronger than those of either drug alone. The present study may provide a new strategy for the long-term treatment of ADPKD.

scholarly journals The NFκB Antagonist CDGSH Iron-Sulfur Domain 2 Is a Promising Target for the Treatment of Neurodegenerative Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 934
Author(s):  
Woon-Man Kung ◽  
Muh-Shi Lin
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Management Strategies ◽  
Nuclear Factor Κb ◽  
Peroxisome Proliferator ◽  
Proinflammatory Response ◽  
Pharmacological Management ◽  
Peroxisome Proliferator Activated Receptor ◽  
Iron Sulfur ◽  
Promising Target

Proinflammatory response and mitochondrial dysfunction are related to the pathogenesis of neurodegenerative diseases (NDs). Nuclear factor κB (NFκB) activation has been shown to exaggerate proinflammation and mitochondrial dysfunction, which underlies NDs. CDGSH iron-sulfur domain 2 (CISD2) has been shown to be associated with peroxisome proliferator-activated receptor-β (PPAR-β) to compete for NFκB and antagonize the two aforementioned NFκB-provoked pathogeneses. Therefore, CISD2-based strategies hold promise in the treatment of NDs. CISD2 protein belongs to the human NEET protein family and is encoded by the CISD2 gene (located at 4q24 in humans). In CISD2, the [2Fe-2S] cluster, through coordinates of 3-cysteine-1-histidine on the CDGSH domain, acts as a homeostasis regulator under environmental stress through the transfer of electrons or iron-sulfur clusters. Here, we have summarized the features of CISD2 in genetics and clinics, briefly outlined the role of CISD2 as a key physiological regulator, and presented modalities to increase CISD2 activity, including biomedical engineering or pharmacological management. Strategies to increase CISD2 activity can be beneficial for the prevention of inflammation and mitochondrial dysfunction, and thus, they can be applied in the management of NDs.

scholarly journals What Differs between Patients under Methadone and under Buprenorphine for Opioid Use Disorder (OUD) in Daily Clinical Practice in France? A Short Report

2021 ◽  
Vol 18 (4) ◽  
pp. 1425
Author(s):  
Morgane Guillou-Landreat ◽  
Antoine Dany ◽  
Gaëlle Challet-Bouju ◽  
Edouard Laforgue ◽  
Juliette Leboucher ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Opioid Use Disorder ◽  
Term Treatment ◽  
Pharmacological Therapy ◽  
Daily Clinical Practice ◽  
Short Report ◽  
Opioid Use ◽  
Cross Sectional ◽  
Long Term Treatment ◽  
Social Profiles

(1) Background: Opioid use disorder (OUD) is a complex condition that can require long-term treatment. Pharmacological therapy for OUD involves treatment with opioid agonists (OMT) tailored to individual profiles. The aim of our study in daily clinical practice was to compare the profiles of patients treated with methadone (MTD) and those using buprenorphine (BHD or BHD-naloxone-NX). (2) Methods: A cross-sectional multicentre study explored the psychological, somatic and social profiles of patients with Opioid Use Disorder (OUD) following Opioid Maintenance Treatment (BHD, BHD/NX, or MTD). Descriptive and comparative analyses were performed (3) Results: 257 patients were included, a majority were men using heroin. 68% (178) were on MTD, 32% (79) were on BHD. Patients with MTD were significantly more likely to report socio-affective damage, and more likely to be younger and not to report oral or sublingual use as the main route for heroin or non-medical opioids (4) Conclusions: In daily clinical practice, regarding OUD damage, only socio-affective damage was significantly more prevalent among patients on MTD than among those on BHD in the multivariate model. Age and route of administration also differed, and our results could raise the issue of the type of OMT prescribed in case of non-medical use of prescribed opioids. These hypothesis should be confirmed in larger studies.

scholarly journals Hypomagnesemia Induced by Long-Term Treatment with Proton-Pump Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Simone Janett ◽  
Pietro Camozzi ◽  
Gabriëlla G. A. M. Peeters ◽  
Sebastiano A. G. Lava ◽  
Giacomo D. Simonetti ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Term Treatment ◽  
Cross Sectional ◽  
Magnesium Metabolism ◽  
Poor Renal Function ◽  
Long Term Treatment

In 2006, hypomagnesemia was first described as a complication of proton-pump inhibitors. To address this issue, we systematically reviewed the literature. Hypomagnesemia, mostly associated with hypocalcemic hypoparathyroidism and hypokalemia, was reported in 64 individuals on long-term proton-pump inhibitors. Hypomagnesemia recurred following replacement of one proton-pump inhibitor with another but not with a histamine type-2 receptor antagonist. The association between proton-pump inhibitors and magnesium metabolism was addressed in 14 case-control, cross-sectional studies. An association was found in 11 of them: 6 reports found that the use of proton-pump inhibitors is associated per se with a tendency towards hypomagnesemia, 2 found that this tendency is more pronounced in patients concurrently treated with diuretics, carboplatin, or cisplatin, and 2 found a relevant tendency to hypomagnesemia in patients with poor renal function. Finally, findings likely reflecting decreased intestinal magnesium uptake were observed on treatment with proton-pump inhibitors. Three studies did not disclose any relationship between magnesium metabolism and treatment with histamine type-2 receptor antagonists. In conclusion, proton-pump inhibitors may cause hypomagnesemia. In these cases, switching to a histamine type-2 receptor antagonist is advised.

CLINICALAND MYCOLOGICAL PROFILE OF ONYCHOMYCOSIS IN A HILLY STATE OF NORTH - EAST INDIA .

2021 ◽  
pp. 41-43
Author(s):  
Subrata kumar Das ◽  
Saptadipa Das
Keyword(s):  
Epidemiological Data ◽  
Common Species ◽  
Term Treatment ◽  
Predisposing Factor ◽  
Cross Sectional ◽  
Diagnostic Strategies ◽  
North East India ◽  
North East ◽  
Number Of Patients ◽  
Long Term Treatment

Background: Onychomycosis is a chronic fungal infection of nger nails and toe nails. It is a non life threatening condition and requires long-term treatment. Mostly patients seek medical care for cosmetic purpose unless it gets secondarily infected and produce pain. Aims: The aim of this study was to determine the prevalence of various causative agents of onychomycosis and to study the clinical and mycological patterns of onychomycosis . Material and Methods: This was a cross sectional observational study which was carried over a period of one year , from December 2019 to November 2020 . A total of 47 patients were included in the study , who visited Dermatology OPD of SMIMS , Sikkim, India. After clinical evaluation , nail samples were subjected for KOH mount and culture. Results:This study included 47 patients of clinically diagnosed onychomycosis , 30 males and 17 males . In the present study maximum number of patients belonged to the age group 30-40 years with 28 patients . Most of the study subjects , 22 were agricultural worker . We found that trauma to the nails was the commonest predisposing factor 17. Out of 47 patients 33 patients were KOH positive and 21 patients were culture positive. Most common type of onychomycosis was Distal lateral subungual onychomycosis with 2 cases . Most common species identied in our study was T.rubram with 5 patients , followed by T. mentagrophytes with 3 patients. Conclusion: Along dermatophytes , NDM and yeasts were also common aetiological agents of onychomycosis. Since onychomycosis can cause physical , psychological and occupational problems, the clinico-epidemiological data can be helpful in development of preventive and diagnostic strategies.

Effectiveness of Long-Term Treatment of Multiple Myeloma in Regular Care: Comparison of a Longitudinal and a Cross-Sectional Analysis Approach

2021 ◽  
pp. 1-8
Author(s):  
Tilman Steinmetz ◽  
Angela Ernst ◽  
Martin Hellmich ◽  
Melanie Heinz ◽  
Uwe Totzke
Keyword(s):  
Multiple Myeloma ◽  
Treatment Guidelines ◽  
Term Treatment ◽  
Subsequent Treatment ◽  
New Drugs ◽  
Event Analysis ◽  
Cross Sectional ◽  
Regular Care ◽  
Long Term Treatment ◽  
Cross Sectional Studies

<b><i>Introduction:</i></b> New drugs for multiple myeloma have considerably increased the options for consecutive treatment lines in regular care. Official treatment guidelines still discuss several regimens per line, and therefore, current practice is of topical interest. Large cross-sectional studies revealed a greater than linear loss of patients reaching consecutive treatment lines of ever decreasing effectiveness. <b><i>Methods:</i></b> In a longitudinal approach, we analyzed data of all 145 multiple myeloma patients treated in our outpatient clinic in Germany between January 1, 2012, and December 31, 2019, using a time-to-event analysis with death as competitive risk. <b><i>Results:</i></b> The estimated incidences of reaching the 2nd, 3rd, 4th, and 5th lines of therapy were 88, 66, 44, and 30%, respectively. Median times to subsequent treatment lines were 34, 18, 14, 13, and 15 months, respectively. <b><i>Discussion:</i></b> Percentages of patients reaching later therapy lines were considerably greater than predicted by cross-sectional studies and median times after the 1st line did not suggest a further decrease in effectiveness, while use of new drug regimens was similar to that reported in cross-sectional studies. <b><i>Conclusion:</i></b> Effectiveness of later therapy lines appears to be underestimated by cross-sectional analyses, and the conveyed focus on 1st-line treatment for multiple myeloma needs to be scrutinized.

Impact of α-lipoic acid on liver peroxisome proliferator-activated receptor-α, vascular remodeling, and oxidative stress in insulin-resistant rats

2011 ◽  
Vol 89 (10) ◽  
pp. 743-751 ◽  
Author(s):  
Adil El Midaoui ◽  
Calin Lungu ◽  
Hui Wang ◽  
Lingyun Wu ◽  
Caroline Robillard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipoic Acid ◽  
Tap Water ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Resistant ◽  
Plasma Ffa ◽  
The Impact

This study sought to determine the impact of α-lipoic acid (LA) on superoxide anion (O2•–) production and peroxisome proliferator-activated receptor-α (PPARα) expression in liver tissue, plasma free fatty acids (FFA), and aortic remodeling in a rat model of insulin resistance. Sprague–Dawley rats (50–75 g) were given either tap water or a drinking solution containing 10% D-glucose for 14 weeks, combined with a diet with or without LA supplement. O2•– production was measured by lucigenin chemiluminescence, and PPAR-α expression by Western blotting. Cross-sectional area (CSA) of the aortic media and lumen and number of smooth muscle cells (SMC) were determined histologically. Glucose increased systolic blood pressure (SBP), plasma levels of glucose and insulin, and insulin resistance (HOMA index). All of these effects were attenuated by LA. Whereas glucose had no effect on liver PPAR-α protein level, it decreased plasma FFA. LA decreased the aortic and liver O2•– production, body weight, and plasma FFA levels in control and glucose-treated rats. Liver PPAR-α protein levels were increased by LA, and negatively correlated with plasma FFA. Medial CSA was reduced in all glucose-treated rats, and positively correlated with plasma FFA but not with SBP or aortic O2•– production. Glucose also reduced aortic lumen area, so that the media-to-lumen ratio remained unchanged. The ability of LA to lower plasma FFA appears to be mediated, in part, by increased hepatic PPAR-α expression, which may positively affect insulin resistance. Glucose-fed rats may serve as a unique model of aortic atrophic remodeling in hypertension and early metabolic syndrome.

The role of cross-sectional echocardiography in Kawasaki disease

1991 ◽  
Vol 1 (3) ◽  
pp. 221-224 ◽  
Author(s):  
José A. Ettedgui ◽  
William H. Neches ◽  
Elfriede Pahl
Keyword(s):  
Kawasaki Disease ◽  
Coronary Arteriography ◽  
Term Treatment ◽  
Left Ventricular ◽  
Arterial Stenosis ◽  
Cross Sectional ◽  
Coronary Aneurysms ◽  
Long Term Treatment ◽  
Clear Delineation

SummaryCross-sectional echocardiography is an essential tool in the evaluation ofchildren with Kawasaki disease, both in the acute and chronic stages. In the acute phase of the illness, it is valuable for diagnosis and management of pancarditis and for the long-term monitoring of pericardial effusions, left ventricular function, and the rare cases of chronic valvar dysfunction. When coronary arterial abnormalities are detected, echocardiography can serially evaluate long-term treatment with drugs which prevent the aggregation of platelets and monitor the resolution of coronary aneurysms. The value of cross-sectional echocardiography, nonetheless, is very limited in the detection of coronary arterial stenosis. Coronary arteriography is still important for the diagnosis of obstructive lesions in the coronary arteries and should be used in conjunction with cross-sectional echocardiography for the appropriate long- term management of children with Kawasaki disease at high risk of developing coronary arterial stenosis. Perhaps, in the future, high resolution transesophageal echocardiography will allow clear delineation of coronary arterial anatomy and specifically stenosis, but its role in the evaluation and management of children with Kawasaki disease remains to be explored.

Sign in / Sign up

Export Citation Format

Share Document