Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein after Roux-en-Y gastric bypass or sleeve gastrectomy: a 1-year prospective observational study.

PURPOSE: Low-grade inflammation in obesity contributes to the development of cardiovascular disease, diabetes mellitus and cancer, and is associated with increased mortality. The purpose of this 1-year prospective observational study was to examine the weight loss effect of bariatric surgery on plasma concentrations of two inflammatory markers, namely high-sensitivity C-reactive protein (hsCRP) and soluble urokinase-type plasminogen activator receptor (suPAR), in patients with obesity. METHODS: Sixteen subjects without obesity and 32 patients with obesity class III, who had already settled upon Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were included in the study. Subjects without obesity were examined once, at baseline; patients with obesity were examined preoperatively (baseline) and 3, 6 and 12 months postoperatively. RESULTS: Plasma suPAR and hsCRP concentrations at baseline were higher in patients with obesity than in lean participants (2.68 ± 0.86 vs 1.86 ± 0.34 ng/mL, p < 0.001 and 9.83 ± 9.55 vs 1.36 ± 1.95 mg/dL, p < 0.001). Levels of suPAR following bariatric surgery increased significantly 3 months after either RYGB or SG (3.58 ± 1.58 vs 3.26 ± 0.7 ng/mL, respectively) and declined at 6 (3.19 ± 1.75 vs 2.8 ± 0.84 ng/mL, respectively) and 12 months (2.6 ± 1.5 vs 2.22 ± 0.49 ng/mL, respectively; p < 0.05 for the effect of time on suPAR levels during the study), whereas those of hsCRP declined consistently after bariatric surgery (3 months: 5.44 ± 3.99 vs 9.47 ± 11.98 mg/dL, respectively; 6 months; 5.39 ± 5.6 vs 10.25 ± 17.22 mg/dL, respectively; and 12 months: 2.23 ± 2.5 vs 3.07 ± 3.63 mg/dL, respectively; p < 0.001 for the effect of time on hsCRP levels during the study). 1-year change in BMI was negatively associated with suPAR levels at 12 months. CONCLUSION: Our findings support an association between obesity and low-grade inflammation. Weight loss following bariatric surgery is associated with a consistent decline in plasma hsCRP, while plasma suPAR levels increase at 3 months and decline by 12 months.

Serum levels of adipokines in gestational diabetes: a systematic review.

OBJECTIVE: To determine the difference of serum levels of 10 adipokines (apelin, chemerin, fatty acid-binding protein-4, fibroblast growth factor-21, monocyte chemoattractant protein-1, nesfatin-1, omentin-1, resistin, vaspin, and visfatin) among women with gestational diabetes and healthy pregnant controls. MATERIALS AND METHODS: Literature search was conducted using the Medline (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2018), Clinicaltrials.gov (2008-2018) and Google Scholar (2004-2018) databases, along with the reference list of the included studies. RESULTS: Ninety-one studies were included in the present review, with a total number of 11,074 pregnant women. A meta-analysis was not conducted due to the high inter-study heterogeneity. Current evidence suggests that fatty acid-binding protein-4 levels are significantly increased in pregnancies complicated with gestational diabetes, while no association of serum apelin and monocyte chemoattractant protein-1 with the disease can be supported. Data regarding the rest adipokines are conflicting, since the available studies did not unanimously indicate a significant change of their levels in gestational diabetes. CONCLUSIONS: The findings of the present systematic review suggest the promising role of fatty acid-binding protein-4 in the prediction of gestational diabetes, while inconsistent evidence exists regarding the rest novel adipokines. Future cohorts are needed to assess their predictive efficacy and fully elucidate their contribution in the disease.

The impact of subcutaneous tissue suturing at caesarean section on wound complications: a meta-analysis.

BACKGROUND: Caesarean wound complications are frequently observed in everyday practice. OBJECTIVES: To study whether subcutaneous tissue closure following caesarean section results in decreased wound complications. SEARCH STRATEGY: We systematically searched Medline (1966-2016), Scopus (2004-2016), ClinicalTrials.gov (2008-2016) and Cochrane Central Register of Controlled Trials CENTRAL (1999-2016) databases together with reference lists from included studies. SELECTION CRITERIA: Randomised and quasi-randomised trials that investigated the impact of subcutaneous tissue suturing on wound complications following caesarean section were held eligible for inclusion. Retrospective studies and prospective nonrandomised studies were excluded from the present meta-analysis. DATA COLLECTION AND ANALYSIS: The methodological quality of studies was assessed with the Jadad scale. Statistical meta-analysis was performed with the RevMan 5.3 software. MAIN RESULTS: Ten studies were finally included in our meta-analysis, which involved 3696 women delivered by caesarean section. Re-approximation of the subcutaneous tissue significantly reduced the odds of developing any type of wound complication [3811 women, random effects model (REM), odds ratio (OR) 0.66, 95% CI 0.47-0.93]. The incidence of seroma was also decreased (1979 women, REM, OR 0.53, 95% CI 0.33-0.84). On the other hand, the incidence of haematoma remained unaffected by subcutaneous closure (1663 women, REM, OR 0.74, 95% CI 0.22-2.42) as well as the likelihood of developing a wound infection (1971 women, REM, OR 0.99, 95% CI 0.70-1.41). CONCLUSIONS: The results of our meta-analysis suggest that subcutaneous tissue closure may benefit women undergoing caesarean section. Current data in women with high body mass index remain very limited; hence, definitive conclusions are precluded for this specific group. TWEETABLE ABSTRACT: Subcutaneous tissue closure may benefit women undergoing caesarean section.

Implementation and effectiveness of the first community lifestyle intervention programme to prevent Type 2 diabetes in Greece. The DE-PLAN study.

AIMS: To report our experience of implementing the first community-based lifestyle intervention programme to detect high-risk individuals and prevent the development of Type 2 diabetes mellitus (T2DM) in a general population sample in Athens, Greece (the DE-PLAN Study). METHODS: The Finnish Type 2 Diabetes Risk Score (FINDRISC) questionnaire was distributed to 7900 people at workplaces and primary-care centres. High-risk individuals were invited to receive an oral glucose tolerance test (OGTT) and, after excluding persons with diabetes, to participate in a 1-year intervention programme, based on bimonthly sessions with a dietitian. RESULTS: Three thousand, two hundred and forty questionnaires were returned; 620 high-risk individuals were identified and 191 agreed to participate. Recruitment from workplaces was the most successful strategy for identifying high-risk persons, enrolling and maintaining them throughout the study. The 125 participants who fully completed the programme (66 did not return for a second OGTT) lost on average 1.0+/-4.7 kg (P=0.022). Higher adherence to the intervention sessions resulted in more significant weight loss (1.1+/-4.8 vs. 0.6+/-4.6 kg for low adherence). Persons with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at baseline lost more weight than those with normal glucose tolerance (1.5+/-4.8 vs. -0.2+/-4.5 kg). The percentage of people with any type of dysglycaemia (IFG/IGT) was lower after the intervention (68.0% at baseline vs. 53.6% 1 year later, P=0.009); 5.6% developed diabetes. CONCLUSIONS: The implementation of a lifestyle intervention programme to prevent T2DM in the community is practical and feasible, accompanied by favourable lifestyle changes. Recruitment from workplaces was the most successful strategy.

The association between the spatial QRS-T angle with cardiac autonomic neuropathy in subjects with Type 2 diabetes mellitus.

AIMS: To examine differences in the spatial QRS-T angle in patients with Type 2 diabetes mellitus with and without cardiac autonomic neuropathy. METHODS: Two hundred and thirty-two patients with diabetes mellitus (105 with cardiac autonomic neuropathy and 127 without cardiac autonomic neuropathy) and 232 control subjects, matched by gender and age, were studied. Diagnosis of cardiac autonomic neuropathy was based on the classic autonomic function tests. All subjects underwent a digital electrocardiographic recording. Electrocardiographic parameters were measured using the Modular Electrocardiographic Analysis (MEANS) program. Left ventricular mass index (LVMi) and global myocardial performance index (Tei index) of the left ventricle were assessed by ultrasonography. RESULTS: The spatial QRS-T angle was higher in the patients with diabetes in comparison with the control subjects (24.5 ± 10.7 vs. 9.7 ± 4.5°, P < 0.001) and in the patients with diabetes and cardiac autonomic neuropathy than in those without cardiac autonomic neuropathy (30.1 ± 11.3 vs. 19.5 ± 7.1, P < 0.001). No differences were found in the QT interval between the studied groups. Multivariate linear regression analysis in subjects with diabetes after controlling for age, gender, BMI, blood pressure, diabetes duration, HbA(1c) , lipids, microalbuminuria and insulin resistance, demonstrated significant and independent associations between the spatial QRS-T angle with presence and severity of cardiac autonomic neuropathy, all parameters of heart rate variability, LVMi and Tei index. CONCLUSIONS: The spatial QRS-T angle is increased in patients with Type 2 diabetes who have cardiac autonomic neuropathy, suggesting increased ventricular arrhythmogenicity, and is associated with the structural and functional properties of the myocardium. Further research is warranted to evaluate its role in cardiovascular risk stratification of patients with diabetes.

Atherosclerosis regression study in rabbits upon olive pomace polar lipid extract administration.

BACKGROUND AND AIMS: Virgin olive oil polar lipid extract (OOPL) and olive pomace polar lipid extract (PPL) have similar antiatherosclerotic effects in cholesterol-fed rabbits. Our aim was to compare the effect of PPL with that of simvastatin on the progression of atherogenesis. METHODS AND RESULTS: Rabbits were fed an atherogenic diet for 6 weeks in order to develop dyslipidemia and atheromatous lesions. Following documentation of these events in random animals (group A, n=6), the remaining were fed for 3 weeks with: standard chow alone (group B, n=6), chow supplemented with PPL (group C, n=6), and chow supplemented with simvastatin (group D, n=6). Blood was collected at 0, 6 and 9 weeks, to determine plasma lipid levels, plasma PAF-AH activity, platelet aggregation (PAF-EC(50)), resistance of plasma to oxidation (RPO) and extent of atheromatous lesions in aortas. The atherogenic diet induced dyslipidemia and increased PAF-AH activity. Dyslipidemia and PAF-activity reduced more effectively in groups C and D. RPO decreased in group B only. PAF-EC(50) values decreased in group C only. Atherogenesis progression in group C was prevented to an extent indistinguishable from that in group D. PAF-AH activity was positively correlated, whereas RPO was negatively correlated with the extent of atheromatous lesions. CONCLUSION: PPL, as a dietary supplement, is equipotent to simvastatin in preventing the progression of atherogenesis.

Acute kidney injury following the concurrent administration of antipseudomonal ß-lactams and vancomycin: a network meta-analysis.

BACKGROUND: Acute kidney injury is a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. OBJECTIVES: This meta-analysis aims to comparatively assess the nephrotoxicity of antipseudomonal ß-lactams when combined with vancomycin. DATA SOURCES: Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. STUDY ELIGIBILITY CRITERIA: Studies evaluating acute kidney injury risk following the concurrent use of antipseudomonal ß-lactams and vancomycin were selected. PARTICIPANTS: Adult and paediatric patients treated in hospital or intensive care unit. INTERVENTIONS: Administration of vancomycin combined with any antipseudomonal ß-lactam. METHODS: Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. RESULTS: Forty-seven cohort studies were included, with a total of 56 984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates than vancomycin monotherapy (odds ratio (OR) 2.05, 95% confidence intervals (CI) 1.17-3.46) and its concurrent use with meropenem (OR 1.84, 95% CI 1.02-3.10) or cefepime (OR 1.80, 95% CI 1.13-2.77). In paediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR 4.18, 95% CI 1.01-17.29) or vancomycin plus cefepime OR 3.71, 95% CI 1.08-11.24). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. CONCLUSIONS: The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.

Serum adiponectin and resistin in rats under three isocaloric diets: The effect of sibutramine.

The aim of the study was to investigate the effects of (1) macronutrients on food intake, body composition and serum resistin and adiponectin and (2) sibutramine(S) on the above parameters in rats fed with isocaloric diets. Three groups of male Wistar rats (n=63) were fed with high fat diet (HFD), high carbohydrate diet (HCD) or high protein diet (HPD) for 13weeks. In the last 3weeks each group was divided into three subgroups and received S 5mg/kg or 10mg/kg, or vehicle. Body weight was measured weekly, gastrocnemius muscle, perirenal, retroperitoneal and epididymal fat were isolated, fat/lean ratio was calculated and serum adiponectin and resistin were assayed. S did not affect lean body mass in any group. HFD was associated with elevated fat/lean ratio regardless of S administration. S at 10mg/Kg decreased fat/lean ratio in the HCD and HPD and adiponectin in the HFD group. S did not affect resistin in any group. Adiponectin was paradoxically elevated in the HFDS10 compared to the HCD or HPD S10 groups. Resistin was lower in the HCD compared to the HPD and HFD groups. Results suggest a preferential effect of S on body fat. The detrimental effect of S on adiponectin can be attributed to its sympathomimetic properties. Adiponectin was paradoxically elevated in the HFD and resistin in the HPD group, results that require further investigation.

The effect of lead intoxication on endocrine functions.

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Malignant pleural effusion and talc pleurodesis. Experimental model regarding early kinetics of talc particle dissemination in the chest after experimental talc pleurodesis.

PURPOSE: Talc remains a commonly used agent for pleurodesis malignant pleural effusion. Nevertheless, it is associated with a 3-9% incidence of pulmonary reactions ranging from simple pneumonitis to acute respiratory distress syndrome (ARDS). The underlying lung pathology and the size and rate of talc particle dissemination have been implicated as the cause of these complications. There seems to be an acknowledged lack of evidence regarding detailed very early intrathoracic talc particle migration. MATERIALS AND METHODS: Thirty white male New Zealand rabbits underwent experimental pleurodesis and were randomly assigned to 3 (A, B, C) study groups (10 in each group). Rabbits were sacrificed 6, 12 and 18 h after talc administration. Samples from both lungs, mediastinum and parietal pleura were obtained. The number of talc crystals (m) deposited was counted and averaged along all slices of the various tissue samples. RESULTS: A high degree of early talc deposition and subsequent epithelial injury in all examined tissues was observed. Diffuse talc deposition occurred in both lungs, but in a different manner. On the side of talc administration, talc particles were deposited in a time-dependent fashion. On the contralateral side, talc was rapidly deposited during the first hours after the procedure, then the rate of deposition decreased, and increased again between 12 and 18 h after the procedure. CONCLUSION: Large-sized talc particles are deposited on both lungs very early after pleurodesis. At the same time inflammatory pulmonary changes appear bilaterally. Despite contradicting data in the literature, these findings should always be kept in mind when performing this procedure in high risk patients.

Paraoxonase-1: Characteristics and Role in Atherosclerosis and Carotid Artery Disease.

Paraoxonase-1 (PON-1) is a calcium-dependent enzyme that is synthesized in the liver and then secreted in blood where it is bound to high density lipoprotein (HDL). PON-1 is a hydrolase with a wide range of substrates, including lipid peroxides. It is considered responsible for many of the antiatherogenic properties of HDL. PON-1 prevents low density lipoprotein (LDL) oxidation, a process that is considered to contribute to the initiation and development of atherosclerosis. PON-1 activity and levels are influenced by gene polymorphisms; of the 2 common variants, one is in position 192 (Q192R) and one in position 55 (M55L). Also, many drugs affect PON-1 activity. The role of PON-1 in carotid atherosclerosis is inconsistent. Some studies show an association of PON-1 polymorphisms with carotid plaque formation, whereas others do not. The aim of this review is to summarize the characteristics of PON-1, its interactions with drugs and its role in atherosclerosis and especially its relationship with carotid artery disease.

Cardiosphere-Derived Cells Attenuate Inflammation, Preserve Systolic Function, and Prevent Adverse Remodeling in Rat Hearts With Experimental Autoimmune Myocarditis.

BACKGROUND: Cardiosphere-derived cells (CDCs) have yielded promising efficacy signals in early-phase clinical trials of ischemic and nonischemic cardiomyopathy. The potential efficacy of CDCs in acute myocarditis, an inflammatory cardiomyopathy without effective therapy, remains unexplored. Given that CDCs produce regenerative, cardioprotective, anti-inflammatory, and anti-fibrotic effects (all of which could be beneficial in acute myocarditis), we investigated the efficacy of intracoronary delivery of CDCs in a rat model of experimental autoimmune myocarditis. METHODS: Lewis rats underwent induction of experimental autoimmune myocarditis by subcutaneous footpad injection of purified porcine cardiac myosin supplemented with Mycobacterium tuberculosis on days 1 and 7. On day 10, rats were randomly assigned to receive global intracoronary delivery of 500 000 CDCs or vehicle. Global intracoronary delivery was performed by injection of cells or vehicle into the left ventricular (LV) cavity during transient occlusion of the aortic root. Rats were euthanized 18 days after infusion. Cardiac volumes and systolic function were assessed by serial echocardiography, performed on days 1, 10, and 28. Myocardial inflammation, T-cell infiltration, and cardiac fibrosis were evaluated by histology. RESULTS: Experimental autoimmune myocarditis was successfully induced in 14/14 rats that completed follow-up. Left ventricular ejection fraction (LVEF) and volumes were comparable on days 1 and 10 between groups. CDC infusion resulted in increased LVEF (81.5% ± 3% vs 65.4% ± 8%, P < .001) and decreased LV end-systolic volume (43 ± 15 vs 100 ± 24 µL, P < .001) compared to placebo administration at 18 days post-infusion. Cardiosphere-derived cell infusion decreased myocardial inflammation (7.4% ± 7% vs 20.7% ± 4% of myocardium, P = .007), cardiac fibrosis (16.6% ± 13% vs 38.1% ± 3% of myocardium, P = .008), and myocardial T-cell infiltration (30.4 ± 29 vs 125.8 ± 49 cells per field, P = .005) at 18 days post-infusion compared to placebo administration. CONCLUSION: Intracoronary delivery of CDCs attenuates myocardial inflammation, T-cell infiltration, and fibrosis while preventing myocarditis-induced systolic dysfunction and adverse remodeling in rats with experimental autoimmune myocarditis.

Beneficial effects of rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus.

AIM: Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients. METHODS: Seventy individuals with Type 2 diabetes were assigned randomly to either a rosiglitazone group (8 mg/day, RG) or a control group (CG) for 6 months. All participants took gliclazide 160 mg plus metformin 1700 mg in stable dose. None of the individuals had diabetic complications or had previously participated in an exercise programme. Anthropometric parameters, VO2 peak, oxygen pulse, glycaemic indices, lipid profile, adiponectin, insulin resistance, blood pressure and serum MMP-9, TIMP-1, TIMP-2 levels were assessed at baseline and at the end of the study. After Bonferroni adjustment, a P-value < 0.017 was assumed to be statistically significant. RESULTS: Rosiglitazone treatment significantly increased VO2 peak (P < 0.0001), the duration of the exercise test (P < 0.0001), oxygen pulse (P = 0.010) and TIMP-2 levels (P = 0.008) in comparison with CG. Insulin resistance, hyperglycaemia, diastolic blood pressure and MMP-9 levels were also reduced (P < 0.017). Fat mass, lipid profile, TIMP-1 levels and MMP9 : TIMP-1 ratio were unaltered after rosiglitazone treatment. There were no significant changes in these parameters in control subjects. In univariate analysis, the rosiglitazone-induced increment of VO2 peak was associated with alterations in plasma adiponectin (r = 0.691), HOMA-IR (r = -0.782) and HbA(1c) (r = -0.676) (P < 0.017). These relationships retained significance after multiple regression analysis (P = 0.005). CONCLUSIONS: Rosiglitazone treatment increases cardiorespiratory fitness and modulates favourably serum adiponectin, MMP-9 and TIMP-2 levels. Whether these effects produce cardiovascular benefits in the long term requires further investigation.

The hamster model of sequential oral oncogenesis.

Oral squamous cell carcinoma (OSCC) is a common cancer characterised by low survival rate and poor prognosis. The multistep process of oral carcinogenesis is affected by multiple genetic events such as alterations of oncogenes and tumour suppressor genes. The use of appropriate experimental animal models that accurately represent the cellular and molecular changes which are associated with the initiation and progression of human oral cancer is of crucial importance. The Syrian golden hamster cheek pouch oral carcinogenesis model is the best known animal system that closely correlates events involved in the development of premalignant and malignant human oral cancers. Therefore, we established an experimental system of chemically induced oral carcinogenesis in hamsters, in order to study different stages of tumour formation: normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. We investigated the expression of oncogenes EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, apoptosis markers Bax and Bcl-2, tumour suppressor genes p53 and p16, and cell proliferation marker Ki-67 in the sequential stages of hamster oral oncogenesis. Here, we describe the findings of the experimental model in regard to the involvement of signal transduction pathways in every stage of cancer development. Increased apoptosis and cell proliferation were observed in early stages of oral oncogenesis. Furthermore, the increased expression of transmembrane receptors (EGFR, erbB2, FGFR-2 and FGFR-3) as well as the increased expression of nuclear transcriptional factors in early stages of oral cancer indicates that these molecules may be used as early prognostic factors for the progression of OSCC. Since the expression of both H-ras and N-ras do not seem to affect signal transduction during oral oncogenesis, it can be assumed that a different signalling pathway, such as the PI3K and/or PLCgamma pathway, may be implicated in the pathogenesis of OSCC.

Laparoscopic bowel injury: role of the site and the instrument type: study with an animal model.

BACKGROUND: Unrecognized laparoscopic bowel injuries are complications that can occur during any laparoscopic procedure. These complications have variable morbidity and mortality rates, and their early clinical signs of inflammation are not typical. Therefore, a study was planned to predict the mechanical behavior of the injured bowel, taking into consideration two parameters: the size of the instrument and the site of the injury. METHODS: For this study, 78 Wistar rats were divided into eight study groups and one control group with two subgroups. Bowel injury was created using different sizes of needles and electrocautery on two different bowel sites: the jejunum and the terminal ileum. The animals were killed 48 h after surgery, followed by harvesting of the injured part of the bowel and measurement of the intraluminal pressure at which the bowel ruptured. RESULTS: The mean jejunum and terminal ileum rupture pressures on the injured bowel were significantly lower than on the intact bowel. The mean terminal ileum rupture pressures were significantly lower than those of the jejunum. CONCLUSIONS: The terminal ileum appears to be more fragile than the jejunum regardless of the size of the instrument that caused the injury. However, wider instrument tips cause more serious consequences.

Adrenaline attenuates the acute lung injury after intratracheal lipopolysaccharide instillation: an experimental study.

Endotoxin is a major cause of endotoxinemia, sepsis, and pneumonia due to gram-negative bacteria. Experimental endotoxin administration via the tracheal route has been extensively used to study the biological and pathophysiologic pathways of inflammation. In particular, experimental endotoxin instillation in the respiratory tree has allowed an extended research with regard to the local response of the lungs to the pathogenic stimulus. This study aims (a) to define early events in the inflammatory cascade and (b) to evaluate the efficacy of adrenaline to ameliorate the acute pulmonary inflammation in vivo after administration of intratracheal lipopolysaccharide (LPS) in an in vivo animal model. Two groups of animals were used for that purpose, a control group (single LPS administration) and a study group (subcutaneous adrenaline infusion following LPS administration). We found that mononuclear recruitment, along with an increased population of CD4+ T lymphocytes, is an early event during the course of LPS-challenged inflammation. In the study group, we determined that adrenaline mediated the lung inflammation in a statistically significant degree. By the use of immunohistochemistry, we identified (1) an increased population of CD4+ T lymphocytes in the inflammatory infiltrate, further endorsing the hypothesis that T-helper lymphocytes, along with macrophages, secrete cytokines which amplify the inflammatory response, and (2) an upregulation of ICAM-1 expression, suggesting an important role in the early pathogenesis of LPS-induced acute lung injury. Our study establishes that systemic adrenaline administration after LPS instillation may ameliorate the inflammatory lung response in vivo.

Effect of isocaloric diets and sibutramine on food intake, body mass variation and serum TNF-alpha levels in rats.

BACKGROUND/AIM: The effect of isocaloric diets and sibutramine on dietary behaviour and TNF-alpha is poorly understood. The aim of the study was to investigate the effects of isocaloric diets and sibutramine on food intake, body mass variation and serum TNF-alpha in free-feeding rats. METHODS: Three groups of male Wistar rats (n = 63) were fed a high-fat diet, high-carbohydrate diet or high-protein diet for 13 weeks. In the last 3 weeks, each group was divided into 3 subgroups. Each subgroup received sibutramine 5 mg/kg, sibutramine 10 mg/kg or vehicle. Food intake was measured daily during the last week of the experiment; serum TNF-alpha was assayed and the body weight increasing rate was calculated. RESULTS: The high-fat diet was associated with increased food intake, a greater weight gain ratio and increased TNF-alpha levels. Sibutramine treatment did not affect the dietary behaviour of high-protein- or high-carbohydrate-fed rats, while it significantly attenuated the daily food intake and body weight gain rate in the high-fat group, at the dose of 10 mg/kg. TNF-alpha levels were not affected by sibutramine. CONCLUSIONS: High-fat feeding was associated with an increase in daily food intake, TNF-alpha levels and body weight gain rate, as well as with enhanced responsiveness to the anorectic effects of sibutramine. However, sibutramine did not affect TNF-alpha.

The use of mice and rats as animal models for cardiopulmonary resuscitation research.

Cardiopulmonary resuscitation (CPR) after the induction of cardiac arrest (CA) has been studied in mice and rats. The anatomical and physiological parameters of the cardiopulmonary system of these two species have been defined during experimental studies and are comparable with those of humans. Moreover, these animal models are more ethical to establish and are easier to manipulate, when compared with larger experimental animals. Accordingly, the effects of successful CPR on the function of vital organs, such as the brain, have been investigated because damage to these vital organs is of concern in CA survivors. Furthermore, the efficacy of several drugs, such as adrenaline (epinephrine), vasopressin and nitroglycerin, has been evaluated for use in CA in these small animal models. The purpose of these studies is not only to increase the rate of survival of CA victims, but also to improve their quality of life by reducing damage to their vital organs after CA and during CPR.

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

Diabetes may increase risk for oral cancer through the insulin receptor substrate-1 and focal adhesion kinase pathway.

In light of recent epidemiological studies that associate diabetes mellitus with increased risk for oral cancer, we investigated in diabetic (type I) and normal rats with induced oral squamous cell carcinoma whether the molecular basis for that putative association involves insulin receptor substrate-1 (IRS-1) and focal adhesion kinase (FAK). Fourteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Oral sections were studied using monoclonal antibodies against IRS-1 and FAK proteins. Expression of IRS-1 was significantly higher in diabetic than normal rats, but it decreased in diabetic animals with tumor, especially in more advanced stages. FAK expression was significantly higher in rats with cancer in comparison to the ones without it, regardless the diabetes status. These data suggest that the IRS-1/FAK pathway is altered by diabetes resulting in reduced cell adhesion and possibly increasing risk for oral cancer.