Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation.

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.

Evaluation of Oxidative Stress Biomarkers, Pro-Inflammatory Cytokines, and Histological Changes in Experimental Hypertension, Dyslipidemia, and Type 1 Diabetes Mellitus.

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.

Comparative Protective Effect of Nigella sativa Oil and Vitis vinifera Seed Oil in an Experimental Model of Isoproterenol-Induced Acute Myocardial Ischemia in Rats.

The study's aim was to characterize the composition of Nigella sativa seed (NSO) and grape seed (GSO) oils, and to evaluate their cardioprotective and anti-inflammatory effect on isoproterenol (ISO)-induced ischemia in rats. Materials and Methods: NSO and GSO supplements were physicochemically characterized. Liquid chromatography-mass spectrometry (HPLC-MS), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography-mass spectrometry (GC-MS) analyses were used to determine the phytochemical composition in the oils. Total polyphenol content (TPC) and in vitro antioxidant activity were also determined. Pretreatment with 4 mL/kg/day NSO or GSO was administered to rats for 14 days. The experimental ischemia was induced by a single administration of ISO 45 mg/kg after 14 days. An electrocardiogram (ECG) was performed initially and 24 h after ISO. Biological evaluation was done at the end of experiment. Results: The HPLC-MS, GC-MS, and FTIR analyses showed that both NSO and GSO are important sources of bioactive compounds, especially catechin and phenolic acids in GSO, while NSO was enriched in flavonoids and thymol derivatives. Pretreatment with GSO and NSO significantly reduced ventricular conduction, prevented the cardiotoxic effect of ISO in ventricular myocardium, and reduced the level of proinflammatory cytokines and CK-Mb. Conclusion: Both NSO and GSO were shown to have an anti-inflammatory and cardioprotective effect in ISO-induced ischemia.

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes.

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus.

Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.

Ginger (Zingiber officinale) Root Capsules Enhance Analgesic and Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation.

Our study aimed to evaluate the analgesic and antioxidant effects of ginger (Zingiber officinale) root capsule extract (GRCE) in addition to diclofenac (D) sodium treatment in carrageenan-induced acute inflammation (AI). Seven groups of eight Wistar-Bratislava white rats were included in the study. One group was the control (C), and AI was induced in the other six groups. The following treatments were applied: saline solution for C and AI groups, D for the AID group, GRCE for two groups and GRCE and D for another two groups. The GRCE was administered by gavage in two doses (100 mg/Kg b.w. or 200 mg/kg b.w.), while D was administered intraperitoneally in a dose of 5 mg/kg b.w. The association of GRCE with this low dose of diclofenac reduced pain threshold and improved mobility with the best results for the dose of 200 mg/kg b.w. Moreover, this combination reduced, better than D alone, the serum levels of the evaluated pro-oxidant parameters (malondialdehyde, the indirect assessment of NO synthesis, total oxidative status and oxidative stress index) up to 78%, especially oxidative stress index (p < 0.0001). GRCE alone slightly improved the antioxidant parameters (total antioxidant capacity and total thiols), but when associated with, D the results were better, especially for total thiols as their plasma levels increased up to 50% (p < 0.0010), with the best results obtained for the 200 mg/kg b.w. dose of GRCE. In conclusion, ginger root capsules associated with diclofenac might offer additional antioxidant and analgesic effects in a dose-dependent manner in acute inflammation.

Transvenous Lead Extraction Procedure-Indications, Methods, and Complications.

Transvenous lead extraction (TLE) is a complex and technically challenging procedure useful in the management strategy for many complications related to the presence of cardiac implantable electronic devices (CIEDs). The decision to perform lead extraction should take into consideration the clinical indication for the procedure, risks versus benefits, extractor and team experience, and also patient preference for the procedure. A variety of techniques can be used when performing TLE procedures, such as simple traction, traction devices, and various types of sheaths or snares. TLE is a procedure with a potentially high risk of complications that can be divided into major complications, which require rapid intervention, and minor complications, which are more frequent but are not life-threatening. The present review aims to highlight the indications, contraindications, methods, and complications of transvenous lead extraction procedures.

Practical Approaches to Transvenous Lead Extraction Procedures-Clinical Case Series.

Transvenous lead extraction (TLE) is regarded as the first-line strategy for the management of complications associated with cardiac implantable electronic devices (CIEDs), when lead removal is mandatory. The decision to perform a lead extraction should take into consideration not only the strength of the clinical indication for the procedure but also many other factors such as risks versus benefits, extractor and team experience, and even patient preference. TLE is a procedure with a possible high risk of complications. In this paper, we present three clinical cases of patients who presented different indications of TLE and explain how the procedures were successfully performed. In the first clinical case, TLE was necessary because of device extravasation and suspicion of CIED pocket infection. In the second clinical case, TLE was necessary because occlusion of the left subclavian vein was found when an upgrade to cardiac resynchronization therapy was performed. In the last clinical case, TLE was necessary in order to remove magnetic resonance (MR) non-conditional leads, so the patient could undergo an MRI examination for the management of a brain tumor.

ECG Markers of Cardiovascular Toxicity in Adult and Pediatric Cancer Treatment.

When a cardiologist is asked to evaluate the cardiac toxic effects of chemotherapy, he/she can use several tools: ECG, echocardiography, coronary angiography, ventriculography, and cardiac MRI. Of all these, the fastest and easiest to use is the ECG, which can provide information on the occurrence of cardiac toxic effects and can show early signs of subclinical cardiac damage. These warning signs are the most desired to be recognized by the cardiologist, because the dose of chemotherapeutics can be adjusted so that the clinical side effects do not occur, or the therapy can be stopped in time, before irreversible side effects. This review addresses the problem of early detection of cardiotoxicity in adult and pediatric cancer treatment, by using simple ECG recordings.

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation.

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)-AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)-AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

Protective Effects of Liposomal Curcumin on Oxidative Stress/Antioxidant Imbalance, Metalloproteinases 2 and -9, Histological Changes and Renal Function in Experimental Nephrotoxicity Induced by Gentamicin.

BACKGROUND: Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. METHODS: Six groups of seven rats were used: C-(control group) received saline solution i.p. (i.p. = intraperitoneal), G-gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2-with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. RESULTS: Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group (p < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC (p < 0.006). CONCLUSIONS: Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.

Microfluidic endothelium-on-a-chip development, from in vivo to in vitro experimental models.

In the last years, animal testing in medical research has been a controversial topic because of various reasons, such as ethical considerations and species differences. Therefore, more attention has been given to develop new technologies that can replace animal experiments and create in vitro models. Organ-on-a-chip (OOC) technology is a new and advanced technology based on microfluidic devices that can mimic the structure and function of entire organs and tissues as in vitro models. OOC models are miniature tissues and organs that assign characteristics for three-dimensional (3D) cell culture representation that resemble the original organs, together with their specific microenvironment microfluidic systems and specific biophysical processes, in order to mimic the normal physiological conditions and functionalities of the organs. Existing OOC models, such as liver, pancreas, heart, skin, brain, kidney, vessels, have been developed and designed for a specific function study. This review focuses on the main knowledge concerning OOC research and especially vascular endothelium-on-a-chip (EOC) model, developed in order to offer specific tools for studying vascular functions in physiological and pathological conditions. The field of OOC devices is still at the beginning, but in the future, this technology may have important roles in developing novel therapeutic approaches, offering new therapeutic molecules and providing the first step towards personalized medicine.

Effect of Liposomal Curcumin on Acetaminophen Hepatotoxicity by Down-regulation of Oxidative Stress and Matrix Metalloproteinases.

BACKGROUND/AIM: The hepatoprotective role of various molecules in drug-induced hepatotoxicity arouses great interest. We investigated the effect of liposomal curcumin (LCC) on experimental acetaminophen (APAP)-induced hepatotoxicity. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups, and the effect of two LCC concentrations was studied: group 1 - 1 ml intraperitoneal (i.p.) saline, group 2 - APAP pretreatment, group 3 - APAP+silymarin (extract of the silybum marianum with anti-inflammatory, anti-oxidant, and anti-fibrotic properties), group 4 - APAP+LCC1, group 5 - APAP+LCC2. The biomarkers of oxidative stress (nitric oxide and malondialdehyde) and antioxidant status of plasma (thiols and catalase), TNF-α, MMP-2 and MMP-9 serum levels were evaluated. RESULTS: An improvement in oxidative stress, antioxidant status, and TNF-α, MMP-2 and MMP-9 levels was obtained in groups pretreated with LCC compared to silymarin treatment, in a dose-dependent manner. Histopathological examination reinforced the results. CONCLUSION: Liposomal curcumin improves the oxidative stress/antioxidant balance and alleviates inflammation in experimental APAP-induced hepatotoxicity.

An Exploratory Association Analysis of ABCB1 rs1045642 and ABCB1 rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban.

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs-treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.

Gender Differences in the Levels of Periodontal Destruction, Behavioral Risk Factors and Systemic Oxidative Stress in Ischemic Stroke Patients: A Cohort Pilot Study.

Background: Due to the higher frequency of ischemic stroke in men compared to women, we aimed to determine if gender differences exist regarding periodontal status and several plasma biomarkers in patients with a recent large artery atherosclerosis ischemic stroke (IS). Material and methods: Patients with their first IS within less than six weeks who were able to undergo periodontal examinations were evaluated. Demographic data, periodontal status, oxidative stress parameters/plasma antioxidant capacity, and C-reactive protein in patients who suffered a recent large artery atherosclerosis ischemic stroke were reccorded. Results: 93 patients were included in the study. More men were smokers (12/57 vs. 3/36) and consumed alcohol (17/57 vs. 3/36), and more women had higher glycemic values (p = 0.023), total cholesterol (p < 0.001), LDL (low-density lipoprotein)-cholesterol (p = 0.010), and HDL (high-density lipoprotein)-cholesterol (p = 0.005) levels. Significantly more men than women had moderate plus severe periodontal disease (p = 0.018), significantly higher levels of nitric oxide (p = 0.034), and significantly lower levels of total antioxidant capacity (p = 0.028). Conclusions: In this pilot study, men seem to be more prone to oxidative stress and to develop more severe forms of periodontitis among patients with stroke, but the results need validation on a larger sample.

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus.

BACKGROUND: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. METHOD: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1-control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2-STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3-STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4-STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). RESULTS: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). CONCLUSIONS: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

Comparative Effect Of Curcumin Versus Liposomal Curcumin On Systemic Pro-Inflammatory Cytokines Profile, MCP-1 And RANTES In Experimental Diabetes Mellitus.

PURPOSE: Anti-inflammatory proprieties of curcumin were proved to be useful in various diseases, including diabetes mellitus. The aim of this study was to assess the anti-inflammatory comparative effect of curcumin solution with liposomal curcumin formula, regarding the improvement of serum levels of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin), IL-1α, IL-1ß, MCP-1 (monocyte chemoattractant protein-1) and RANTES in experimental diabetes, induced by streptozotocin (STZ), in rats. MATERIALS AND METHODS: Six groups of 7 rats were investigated regarding the effect of i.p. (intraperitoneal) administration of two concentrations of curcumin solution (CC1 and CC2) and two concentrations of liposomal curcumin (LCC1 and LCC2): group 1 - control group with i.p. administration of 1 mL saline solution, group 2 - i.p. STZ administration (60mg/kg bw, bw=body weight), group 3 - STZ+CC1 administration, group 4 - STZ+CC2 administration, group 5 - STZ+ LCC1 administration and group 6 - STZ+ LCC2 administration. The concentrations of curcumin formulas were 1 mg/0.1 kg bw for CC1 and LCC1 and 2 mg/0.1 kg bw for CC2 and LCC2, respectively. Serum levels of C-peptide (as an indicator of pancreatic function) and TNF-α, IL-6, IL-1α, IL-1ß, MCP-1, and RANTES (as biomarkers for systemic inflammation) were assessed for each group. RESULTS: The plasma level of C-peptide showed significant improvements when LCC was administrated, with better results for LCC2 when compared to LCC1 (P<0.003). LCC2 pretreatment proved to be more efficient in reducing the level of TNF-α (P<0.003) and RANTES (P<0.003) than CC2 pretreatment. Upon comparing LCC2 with LCC1 formulas, the differences were significant for TNF-α (P=0.004), IL-1ß (P=0.022), and RANTES (P=0.003) levels. CONCLUSION: Liposomal curcumin in a dose of 2 mg/0.1 kg bw proved to have an optimum therapeutic effect as a pretreatment in DM induced by STZ. This result can constitute a base for clinical studies for curcumin efficiency as adjuvant therapy in type 1 DM.

Catheter ablation of a right posterior accessory pathway in a patient with left ventricular noncompaction: A case report.

RTIONALE: Left ventricular noncompaction (LVNC) is a genetic cardiomyopathy characterized by the presence of a thin compacted layer of myocardium and a spongy subendocardial layer with trabeculations and recesses. LVNC associated Wolf-Parkinson-White syndrome is very rare. PATIENT CONCERNS: A 32-year-old male presented with short episodes of palpitations and a syncope 6 months before his hospitalization. DIAGNOSIS: His ECG revealed the presence of a right posterior accessory pathway. Echocardiography identified trabeculations of the septal, apical, and lateral wall of the left ventricle, consistent with left ventricular noncompaction. Cardiac MRI confirmed the diagnosis, as the ratio between the noncompacted and compacted myocardial layer was 2.3. INTERVENTIONS: The electrophysiological study revealed a malignant right posterior accessory pathway. Catheter ablation was successfully performed at the level of posterior tricuspid annulus. Programmed ventricular stimulation could not induce any arrhythmia at the end of the procedure. OUTCOMES: During 15 months of follow-up, the patient presented no more episodes of palpitations or syncope. LESSONS: Left ventricular noncompaction with right accessory pathway is a rare association with genetic basis and gives a higher risk of sudden cardiac death. Catheter ablation of the accessory pathway is a valuable way of treatment in this category of patients, lowering the risk of sudden cardiac death.

Effects of Curcumin Nanoparticles in Isoproterenol-Induced Myocardial Infarction.

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1ß, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.