Effect of a new squalene synthase inhibitor on an ApoE-/- mouse model of atherosclerosis.

Ηypercholesterolemia/hyperlipidemia in conjunction with oxidative stress and inflammatory processes contribute synergistically to the pathogenesis of atherosclerosis. We hereby evaluated the antiatherosclerotic effect of the multi-target derivative 4-methyl-2-(10H-phenothiazin-3-yl)morpholin-2-ol hydrobromide 1 in apoE-/- mice; compound 1 is a potent antihyperlipidemic agent acting through Squalene Synthase inhibition, while it has exhibited an outstanding antioxidant and anti-inflammatory activity in various experimental animal models. The new analogue was evaluated in terms of its antiatherosclerotic/antioxidant effect in the ApoE-/- transgenic mouse model. Its toxicity profile was also assessed by measuring the levels of four sensitive indicators of liver toxicity. Prolonged administration of 1 in ApoE-/- mice fed with a western-type (wt) diet efficiently reduced the aortic atheromatic lesions, an effect that took place through a cholesterol lowering independent manner. In addition, 1 displayed a significant reduction not only of glucose but also of oxidative stress levels, while it did not cause any toxicity. To the best of our knowledge this is the first time that the antiatherosclerotic effect of a Squalene Synthase inhibitor is studied in this specific atherosclerosis mouse model. As a result, compound 1 may serve as a promising starting point towards developing new bioactive analogues against the onset and subsequent development of atherosclerosis.

Rosuvastatin Attenuates Progression of Atherosclerosis and Reduces Serum IL6 and CCL2 Levels in Apolipoprotein-E-deficient Mice.

BACKGROUND/AIM: Apolipoprotein E-deficient (Apoe-/-) mice develop atherosclerotic lesions that closely resemble metabolic syndrome in humans. We sought to investigate how rosuvastatin mitigates the atherosclerotic profile of Apoe-/- mice over time and its effects on certain inflammatory chemokines. MATERIALS AND METHODS: Eighteen Apoe-/- mice were allocated into three groups of six mice each receiving: standard chow diet (SCD; control group); high-fat diet (HFD); and HFD and rosuvastatin at 5 mg/kg/d orally via gavage for 20 weeks. Analysis of aortic plaques and lipid deposition was conducted by means of en face Sudan IV staining and Oil Red O staining. Serum cholesterol, low-density lipoprotein, high-density lipoprotein, plasma glucose and triglyceride levels were determined at baseline and after 20 weeks of treatment. Serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2) and tumor necrosis factor-α (TNFα) levels were measured by enzyme-linked immunosorbent assay at the time of euthanasia. RESULTS: The lipidemic profile of Apoe-/- mice on HFD deteriorated over time. Apoe-/- mice on HFD developed atherosclerotic lesions over time. Sudan IV and Oil Red O-stained sections of the aorta revealed increased plaque formation and plaque lipid deposition in HFD-fed mice compared with SCD-fed mice and reduced plaque development in HFD-fed mice treated with rosuvastatin compared with mice not receiving statin treatment. Serum analysis revealed reduced metabolic parameters in HFD-fed mice on rosuvastatin compared with non-statin, HFD-fed mice. At the time of euthanasia, HFD-fed mice treated with rosuvastatin had significantly lower IL6 as well as CCL2 levels when compared with HFD-fed mice not receiving rosuvastatin. TNFα levels were comparable among all groups of mice, irrespective of treatment. IL6 and CCL2 positively correlated with the extent of atherosclerotic lesions and lipid deposition in atherosclerotic plaques. CONCLUSION: Serum IL6 and CCL2 levels might potentially be used as clinical markers of progression of atherosclerosis during statin treatment for hypercholesterolemia.

[The effects of carotid revascularization on mood symptoms and quality of life in patients with high - grade carotid stenosis].

Carotid occlusive disease has been related to ischaemic strokes and cerebral hypoperfusion, thus affecting patients' quality of life, mainly because of cognitive decline and depressive symptoms. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may, postoperatively, have a positive impact on patients' quality of life and mental condition, though there have been also presented elusive findings and controversial results. The aim of the present study is to evaluate the effect of carotid revascularization (CEA, CAS) on patients' psychological condition and quality of life through a baseline and follow-up examination. We present data of a group of 35 patients (age range:60-80 years, ΜA=70,26-SD=9,05) with severe, left or right, carotid artery stenosis (>75%), presented with or without symptoms, who underwent surgical treatment with CEA or CAS. Baseline and follow-up (6 months post-surgery) evaluation was conducted in order to assess patients' depressive symptoms and quality of life, through completion of the Beck Depression Inventory and WHOQOL-BREF Inventory, respectively. No statistically significant (p < 0,05) effect of the revascularization process on mood or quality of life assessment could be documented for our patients, regardless of the applied technique (CAS or CEA). Our study supports existing evidence that all of the traditional vascular risk factors represent active participants in the inflammatory process, which has also been implicated in the pathophysiology of depression as well as in pathogenesis of atherosclerotic processes. Thus we have to illuminate new links between the two nosological entities, in the crossroads of psychiatry, neurology and angiology, through the pathways of inflammatory reactions and endothelium dysfunctions. Even though the effects of carotid revascularization on patient's mood and quality of life, are often characterized by opposing results, pathophysiological processes of "vascular depression" and "post stroke depression" remain a promising interdisciplinary medical domain, sharing both scientific and clinical interests between the fields of neurosciences and vascular medicine. Our results, regarding the bilateral connection of depression and carotid artery disease, advocate a most probable causality link between atherosclerotic process and depressive symptoms, rather than justifying a direct association between depressive disorders and carotid stenosis and inferred cerebral blood flow reduction per se.

Angiotensin II Blood Serum Levels in Piglets, after Intra-Dermal or Intra-Muscular Vaccination against PRRSV.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces apoptosis in different organs. Angiotensin II (Ang II) is the main effector of the renin-angiotensin system and participates in apoptosis. Thus, this study aimed to investigate changes in piglet serum Ang II levels following intradermal (ID) and intramuscular (IM) vaccination with a commercial PRRS modified live virus (MLV) vaccine. The trial was conducted in a commercial pig farm, including 104 piglets which were randomly allocated to four groups: Group A-Porcilis PRRS ID, Group B-Porcilis PRRS IM, Group C-Diluvac ID and Group D-Diluvac IM. The study piglets were either vaccinated or injected at 2 weeks of age and they were tested by qRT-PCR for PRRSV and by ELISA for Ang II. The results indicated differences in viremia of tested piglets at 7 weeks of age, while piglets at 10 weeks of age were all found qRT-PCR positive for PRRSV. In addition, significant differences were noticed in Ang II in 7-week-old piglets. In conclusion, the present study provides evidence that ID vaccination induces less tissue damage, based on the lower measurements of Ang II in the serum of ID vaccinated piglets.

Coordinated activation of TGF-ß and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication.

Ligands of the transforming growth factor-ß (TGF-ß) superfamily, including TGF-ßs, activins, and bone morphogenetic proteins (BMPs), have been implicated in hepatic development, homeostasis, and pathophysiology. We explored the mechanisms by which hepatocytes decode and integrate injury-induced signaling from TGF-ßs and activins (TGF-ß/Activin) and BMPs. We mapped the spatiotemporal patterns of pathway activation during liver injury induced by acetaminophen (APAP) in dual reporter mice carrying a fluorescent reporter of TGF-ß/Activin signaling and a fluorescent reporter of BMP signaling. APAP intoxication induced the expression of both reporters in a zone of cells near areas of tissue damage, which showed an increase in autophagy and demarcated the borders between healthy and injured tissues. Inhibition of TGF-ß superfamily signaling by overexpressing the inhibitor Smad7 exacerbated acute liver histopathology but eventually accelerated tissue recovery. Transcriptomic analysis identified autophagy as a process stimulated by TGF-ß1 and BMP4 in hepatocytes, with Trp53inp2, which encodes a rate-limiting factor for autophagy initiation, as the most highly induced autophagy-related gene. Collectively, these findings illustrate the functional interconnectivity of the TGF-ß superfamily signaling system, implicate the coordinated activation of TGF-ß/Activin and BMP pathways in balancing tissue reparatory and regenerative processes upon APAP-induced hepatotoxicity, and highlight opportunities and potential risks associated with targeting this signaling system for treating hepatic diseases.

Investigation of Fas (APO-1)-Related Apoptosis in Piglets Intradermally or Intramuscularly Vaccinated with a Commercial PRRSV MLV.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces apoptosis through the activation of death receptors, including cell-surface Fas receptor. The aim of this study was to investigate the impact of intradermal (ID) and intramuscular (IM) vaccination with a commercial PRRSV-modified live vaccine in piglets on Fas-related apoptosis. The study included 104 suckling piglets from a commercial farrow-to-finish pig farm, suffering from positive unstable PRRSV status. Animals were assigned in four groups: group A-Porcilis PRRS ID-vaccinated pigs, group B-Porcilis PRRS IM-vaccinated pigs, group C-Diluvac ID adjuvant-administered pigs, and group D-Diluvac IM adjuvant-administered pigs. Vaccines were administered at 2 weeks of age. Blood samples were collected from the same pigs at 4, 7, and 10 weeks of age. Sera were examined by quantitative real-time reverse transcription-PCR (qRT-PCR) for PRRSV and by ELISA for soluble Fas (sFas). At 4 weeks of age, all groups were negative qRT-PCR for PRRSV; at 7 weeks only group A was negative; and at 10 weeks all groups were positive. sFas was significantly increased in groups C (4 vs. 7, 4 vs. 10, and 7 vs. 10 weeks) and D (7 vs. 10 weeks). Significant differences among groups were noticed only at 10 weeks (A vs. C, A vs. D, B vs. C, B vs. D). A significant positive and moderate correlation between PRRSV viral load and Fas level was observed. In unvaccinated piglets, increased serum sFas levels reveal apoptotic suppression compared with vaccinated piglets. In the latter, vaccine-derived antibodies limit the infection and may attribute to the reduced Fas expression, suggesting a weak induction of lymphocyte-mediated cytotoxicity.

CurveletTransform-Based Texture Analysis of Carotid B-mode Ultrasound Images in Asymptomatic Men With Moderate and Severe Stenoses: A Preliminary Clinical Study.

The curvelet transform, which represents images in terms of their geometric and textural characteristics, was investigated toward revealing differences between moderate (50%-69%, n = 11) and severe (70%-100%, n = 14) stenosis asymptomatic plaque from B-mode ultrasound. Texture features were estimated in original and curvelet transformed images of atheromatous plaque (PL), the adjacent arterial wall (intima-media [IM]) and the plaque shoulder (SH) (i.e., the boundary between plaque and wall), separately at end systole and end diastole. Seventeen features derived from the original images were significantly different between the two groups (4 for IM, 3 for PL and 10 for SH; 9 for end diastole and 8 for end systole); 19 of 234 features (2 for IM and 17 for SH; 8 for end systole and 11 for end diastole) derived from curvelet transformed images were significantly higher in the patients with severe stenosis, indicating higher magnitude, variation and randomness of image gray levels. In these patients, lower body height and higher serum creatinine concentration were observed. Our findings suggest that (a) moderate and severe plaque have similar curvelet-based texture properties, and (b) IM and SH provide useful information about arterial wall pathophysiology, complementary to PL itself. The curvelet transform is promising for identifying novel indices of cardiovascular risk and warrants further investigation in larger cohorts.

Kidney biopsy findings in vancomycin-induced acute kidney injury: a pooled analysis.

BACKGROUND: Acute kidney injury represents a major adverse effect of vancomycin administration. The aim of the present study is to accumulate all biopsy-proven cases of vancomycin nephrotoxicity and assess the association of histopathological features with renal prognosis. METHODS: Medline, Scopus, CENTRAL, Web of Science, and Clinicaltrials.gov were systematically searched from inception to 29 September 2020. All case reports/series providing individual data of patients with biopsy-proven vancomycin nephrotoxicity were held eligible. A time-to-event analysis was performed evaluating the effects of histological diagnosis on renal recovery. RESULTS: Overall, 18 studies were included, comprising 21 patients. Acute tubulointerstitial nephritis was the predominant pattern in 9 patients and was associated with a significantly higher risk of permanent renal dysfunction (HR: 5.08, 95% CI: [1.05-24.50)] compared to acute tubular necrosis. Tubulitis and eosinophilic infiltration were the most common histopathological findings, while interstitial fibrosis was linked to significantly worse renal prognosis (HR: 5.55, 95% CI: 1.13-27.27). Immunofluorescence and electron microscopy features were non-specific. Obstruction by tubular casts composed of vancomycin aggregates and uromodulin has been identified as a new mechanism of nephrotoxicity. CONCLUSIONS: Acute tubular necrosis and tubulointerstitial nephritis represent the main histological patterns of vancomycin-induced acute kidney injury. The presence of fibrosis in the context of interstitial inflammation may be linked to lower recovery rates and worse long-term renal outcomes. A novel cast nephropathy obstructive mechanism has been suggested, necessitating further confirmation. Large-scale studies should define the exact indications of kidney biopsy in cases with suspected vancomycin nephrotoxicity.

Comparative efficacy of fixed-dose statin and antihypertensive agent combinations: A network meta-analysis of randomized controlled trials.

BACKGROUND: The concurrent administration of statins and antihypertensive agents has been associated with improved cardiovascular outcomes, although the optimal fixed-dose combination remains unclear. This meta-analysis aims to compare the blood pressure and lipid-lowering effects of various statin and antihypertensive drug combinations. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 20 March 2021. Randomized controlled trials evaluating the effects of statin-antihypertensive agent combinations on systolic blood pressure or serum lipids were held eligible. A random-effects frequentist model was applied to provide estimates of mean difference of percentage change. RESULTS: Overall, 18 studies were included, comprising 4450 patients. Compared to statin monotherapy no significant difference in the percentage change of low-density lipoprotein cholesterol was achieved by adding any antihypertensive agent. Compared to amlodipine monotherapy, the addition of moderate-intensity statin resulted in a significantly greater percentage reduction of systolic blood pressure (-2.22%, 95% confidence intervals: [-3.82 to -0.62]). Combined high-intensity statin and amlodipine lead to significant increase of high-density lipoprotein cholesterol (8.34%, 95% confidence intervals: [0.73 to 15.95]), while effective triglyceride reduction was achieved by adding amlodipine and telmisartan to high-intensity statin (-14.68%, 95% confidence intervals: [-28.48 to -0.89]). No significant difference of adverse effects was observed. CONCLUSION: The present network meta-analysis suggests that the administration of fixed-dose combinations of statins and antihypertensive agents is safe and effective in reducing blood pressure and serum lipids. The optimal dosing strategy to prevent cardiovascular events remains to be determined.

Reduced global longitudinal strain at rest and inadequate blood pressure response during exercise treadmill testing in male heterozygous familial hypercholesterolemia patients.

BACKGROUND: Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging. PATIENTS-METHODS: We evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained. RESULTS: heFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p < 0.001, respectively). Mean rate pressure product was significantly higher in heFH patients (p = 0.038). Both duration of the ETT and workload in metabolic equivalents was lower in the heFH group (p < 0.001 and p < 0.001, respectively). Baseline to peak rise of systolic and diastolic BP in heFH men was higher (p = 0.008 and p < 0.001 for systolic and diastolic BP, respectively). Furthermore, heFH men had higher rise of HR from baseline to peak, compared to controls; (p = 0.047). GLS in heHF men was slightly decreased (p = 0.014), although the ejection fraction was similar in both groups. CONCLUSION: heFH men have a higher rise in systolic/diastolic BP during ETT, which may reflect early, preclinical hypertension. Furthermore, slight impairment of LV GLS is present, despite the absence of apparent myocardial dysfunction in conventional 2D echocardiography.

The Effect of TISSEELTM on Confined Bowel Perforation: An Experimental Study.

OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats. METHODS: Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups: the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice. RESULTS: The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups. CONCLUSION: Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

Possible Roles of Vitamin D in Bone Grafting.

Bone grafting is one of the most commonly used options to treat large bone defects. Evidence has shown that vitamin D may affect osseointegration, a major component for successful bone grafting. In vitro studies have proved that implants coated with activated vitamin D stimulate bone production and reduce bone resorption around implants. Animal studies have noticed that oral administration of vitamin D may stimulate bone formation as well as strengthen and support the interaction between bone and implants. Vitamin D insufficiency may affect negatively the cortical peri-implant bone formation, suggesting a negative effect in graft incorporation. Few clinical studies have observed that vitamin D administration enhanced graft incorporation and bone formation, while severe vitamin D deficiency is associated with failed implant osseointegration. Even though there are encouraging results of vitamin D supplementation on graft incorporation in animal studies, the use of vitamin D as an adjuvant in bone grafting procedures cannot be fully supported at the moment. However, there is theoretical support in the use of vitamin D after surgery and the use of bone grafts to support the bone structure, relieve pain and increase graft absorption. Further experimental and clinical studies are required to support the administration of vitamin D and its analogues in such cases.

The Effect of Prenatal Food Restriction on Brain Proteome in Appropriately Grown and Growth Restricted Male Wistar Rats.

BACKGROUND: Fetal growth restriction (FGR) has been associated with a higher risk of developing adverse perinatal outcomes and distinct neurodevelopmental and neurobehavioral disorders. The aim of the present study was to investigate the impact of prenatal food restriction on the brain proteome in both FGR and appropriately grown rats and to identify potential pathways connecting maternal malnutrition with altered brain development. METHODS: Ten time-dated pregnant Wistar rats were housed individually at their 12th day of gestation. On the 15th day of gestation, the rats were randomly divided into two groups, namely the food restricted one (n = 6) and the control group (n = 4). From days 15 to 21 the control group had unlimited access to food and the food restricted group was given half the amount of food that was on average consumed by the control group, based on measurements taken place the day before. On the 21st day of gestation, all rats delivered spontaneously and after birth all newborn pups of the food restricted group were weighed and matched as appropriately grown (non-FGR) or growth restricted (FGR) and brain tissues were immediately collected. A multiplex experiment was performed analyzing brain tissues from 4 FGR, 4 non-FGR, and 3 control male offspring. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis in order to identify over-represented processes. RESULTS: Proteomic analysis resulted in the profiling of 3,964 proteins. Gene ontology analysis of the common DEPs using DAVID (https://david.ncifcrf.gov/) showed significant enrichment for terms related to cellular morphology, learning, memory and positive regulation of NF-kappaB signaling. Ingenuity Pathway Analysis showed significant induction of inflammation in FGR pups, whereas significant induction of cell migration and cell spreading were observed in non-FGR pups. CONCLUSION: This study demonstrated that in both FGR and non-FGR neonates, a range of adaptive neurodevelopmental processes takes place, which may result in altered cellular morphology, chronic stress, poor memory and learning outcomes. Furthermore, this study highlighted that not only FGR, but also appropriately grown pups, which have been exposed to prenatal food deprivation may be at increased risk for impaired cognitive and developmental outcomes.

Regulation of Long Non-Coding RNAs by Statins in Atherosclerosis.

Despite increased public health awareness, atherosclerosis remains a leading cause of mortality worldwide. Significant variations in response to statin treatment have been noted among different populations suggesting that the efficacy of statins may be altered by both genetic and environmental factors. The existing literature suggests that certain long noncoding RNAs (lncRNAs) might be up- or downregulated among patients with atherosclerosis. LncRNA may act on multiple levels (cholesterol homeostasis, vascular inflammation, and plaque destabilization) and exert atheroprotective or atherogenic effects. To date, only a few studies have investigated the interplay between statins and lncRNAs known to be implicated in atherosclerosis. The current review characterizes the role of lncRNAs in atherosclerosis and summarizes the available evidence related to the effect of statins in regulating lncRNAs.

Markers of endothelial dysfunction and arterial stiffness in patients with early-stage autosomal dominant polycystic kidney disease: A meta-analysis.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is characterised by increased rates of cardiovascular complications leading to significant morbidity and mortality. This meta-analysis aims to evaluate whether the disease is linked to endothelial dysfunction and arterial stiffness during its early stages. METHODS: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov and Google Scholar databases comparing ADPKD patients with preserved renal function to healthy controls were included. The outcomes of interest were brachial flow-mediated dilatation, carotid-femoral pulse wave velocity, augmentation index, carotid intima-media thickness and central systolic blood pressure, plasma ADMA or homocysteine levels. Standardised mean differences (SMDs) were estimated by a random-effects model in R-3.6.3. RESULTS: A total of 27 studies were included, comprising 1967 individuals. ADPKD was linked to significantly lower flow-mediated dilatation (SMD: -1.44, 95% CI: [-2.35, -0.53]) and higher pulse wave velocity (SMD: 1.44, 95% CI: [0.22, 2.66]) and carotid intima-media thickness (SMD: 1.02, 95% CI: [0.57, 1.47]). No significant associations were noted regarding augmentation index (SMD: 0.62, 95% CI: [-0.19, 1.43]) and central systolic blood pressure (SMD: 1.84, 95% CI: [-0.12, 3.80]). Plasma homocysteine was significantly higher in ADPKD (SMD: 0.81, 95% CI: [0.16, 1.45]), while no difference was calculated for ADMA levels (SMD: 1.14, 95% CI: [-0.25, 2.53]). CONCLUSIONS: Early-stage ADPKD patients present increased vascular stiffness and endothelial dysfunction, as reflected by low flow-mediated dilatation and elevated values of pulse wave velocity, carotid intima-media thickness and plasma homocysteine. The exact effects of early arterial stiffness on long-term outcomes remain to be elucidated.

Intrathoracic schwannoma originating from intrathoracic vagus nerve.

In differential diagnosis of posterior mediastinal mass should be included the intrathoracic vagus nerve tumor. Surgical excision of intrathoracic vagus nerve schwannoma is associated with a low recurrence rate and excellent long-term results.

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice.

The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and Sideritis (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals' overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.

Blood Plasma Resistin and Atrial Fibrillation in Patients With Cardiovascular Disease.

BACKGROUND: Atrial fibrillation (AF) affects quality of life and prognosis of patients with cardiovascular disease. Resistin plays an important role in inflammatory response to internal and external factors. The aim of this study is to evaluate the association between resistin and permanent AF (PAF) in patients with cardiovascular disease. METHODS: In our study, we included 146 patients with cardiovascular disease. Plasma resistin concentrations and demographic characteristics of patients were recorded. The patients were divided in two groups: 118 patients without a history of PAF (NonAF group), and 28 patients with a history of PAF (AF group). Association of resistin with PAF and other variables was examined by parametric and non-parametric tests, and multivariable linear and univariable logistic regression analysis. RESULTS: No differences of demographic characteristics (gender, age and body mass index (BMI)) between two groups were observed (P > 0.05). Higher median levels of resistin were observed in group AF than in group NonAF (6.90 ng/mL vs. 5.83 ng/mL, P = 0.03). Multivariate linear regression analysis (adjusted to gender, age, BMI, hypertension, diabetes mellitus, coronary artery disease, and mitral valve disease) showed that resistin was associated with PAF (ß = 0.79, 95% confidence interval (CI): 0.08 to 1.51, P = 0.03). CONCLUSIONS: Our analysis showed that plasma resistin was associated with PAF, and resistin concentration was higher in patients with AF compared to those without AF.

Metabolic Response of Adult Male Offspring Rats to Prenatal Caffeine Exposure.

Caffeine is the most widely consumed psychoactive substance, with recommendations from health associations and regulatory bodies for limiting caffeine consumption during pregnancy being increasingly common. Prenatal exposure to caffeine has been shown to increase the risk of developing abnormalities in lipid metabolism in adult life. We further investigated the effect of prenatal caffeine exposure (PCE) (20 mg/kg of body weight) on the metabolic "reserve" of male Sprague Dawley offspring fed on a high fructose diet in adult life. Male adult PCE offspring were assigned to four groups; Nw and Nf: offspring of control mothers (N group of mothers), having received tap water or high fructose water respectively; Cw and Cf: offspring exposed to caffeine during gestation (C group of mothers) and receiving tap water or a high fructose water solution, respectively. Cf rats presented increased serum triglyceride level, as well as raised systolic and diastolic blood pressure levels, together with extensive renal tissue oedema in adulthood, compared to the other groups (p<0.05 for all comparisons). These findings show further evidence for potential detrimental metabolic effects of prenatal caffeine exposure during adulthood in this animal model.

Current challenges in the diagnosis and treatment of cardiac myxoma.

Cardiac myxoma is the most common benign cardiac tumor. It is located in the left atrium and typically arises from the foramen ovale in approximately 75% of the general patient population, in the right atrium in 23%, and in the ventricles in only 2%. Symptoms depend on its size, mobility, and relation to surrounding cardiac structures. Neurological complications resulting from cardiac myxoma are seen in 20% to 25% of patients. Molecular genetic studies show that the condition can be inherited in Carney complex due to mutations of the PRKAR1A gene. Cardiac myxoma resection is a cardiac surgery with a low complication rate and the 30­day mortality of up to 10%. Recurrence may be observed months or years after surgery, and its rate is approximately 5%. Long­term follow­up with transthoracic echocardiography is needed in all patients after tumor resection. This review summarizes the available data on cardiac myxoma and, in particular, issues relating to diagnosis and treatment.