ForePass endoscopic bypass device for obesity and insulin resistance-metabolic treatment in a swine model

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Interferon-γ Regulates the Proliferation and Differentiation of Mesenchymal Stem Cells via Activation of Indoleamine 2,3 Dioxygenase (IDO)

The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-β) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Effects of high-fat diet exposure during fetal life on type 2 diabetes development in the progeny

Nutrition during fetal life is a critical factor contributing to diabetes development in adulthood. The aim of our study was to verify: 1) whether a high-fat (HF) diet in young adult mice induces alterations in beta-cell mass, proliferation, neogenesis, and apoptosis, as well as insulin sensitivity and secretion; 2) whether these alterations may be reversible after HF diet suspension; 3) the effects in a first (F1) and second generation (F2) of mice without direct exposure to a HF diet after birth. Type 2 diabetes developed in adult mice on a HF diet, in F1 mice that were HF diet-exposed during fetal or neonatal life, and in F2 mice whose mothers were HF diet-exposed during their fetal life. beta-cell mass, replication, and neogenesis were high in HF diet-exposed mice and decreased after diet suspension. beta-cell mass and replication remained high in F1 mice and decreased in F2 mice whose mothers were exposed to a HF diet. beta-cell neogenesis was present in adult mice on a HF diet and in F1 mice that were HF diet-exposed during fetal and/or neonatal life. We conclude that a HF diet during fetal life, particularly if combined with the same insult during the suckling period, can induce the type 2 diabetes phenotype, which can be directly transmitted to the progeny even in the absence of additional dietary insults

A percutaneous method for single catheter recording of multiple Monophasic action potentials from the epicardial surface in intact anesthetized rodents

A surgical method for programmed electrical stimulation (PES) in mice has been reported by Gutstein et al (2003). We developed a percutaneous approach to record multiple epicardial monophasic action potentials (multi-MAP) in rodents, with a single amagnetic catheter (AC). Methods: Under 6 ECG leads monitoring the AC was introduced with a sub-xyphoid puncture, in 5 anesthetized, spontaneously breathing, Wistar rats (WR) and 5 guinea pigs (GP). The AC was moved at several epicardial sites. 4 MAPs were simultaneously recorded at each site with a fixed (1 mm) inter-electrode distance. MAP signals, differentially amplified and filtered at DC-500 Hz were digitized at 1kHz. The same AC was used for PES at pacing cycles between 200 and 250 ms. Ventricular effective refractory period (VERP) was evaluated with the accuracy of 2 ms. MAP duration (MAPd), at 50% and 90% levels of repolarization, and local activation time among the four MAPs were calculated. Results: All but one animal tolerated the procedure and survived. One rat died for respiratory arrest at the moment of the puncture. One rat was restudied after 6 months and survived also the second procedure. MAPd 90% (ms) were: 69±5.6 (WR) and 172±12.3 (GP). VERP were: 67±9.4 (WR) and 155±15.6 (GP). Conclusion: The percutaneous approach avoids cut-down, is well tolerated and keeps animals alive and available for longitudinal investigations. The multi-MAP method provides information about arrhythmogenic mechanisms (i.e. MAPd/ERP ratio, detection of ventricular repolarization (VR) inhomogeneity and of local block), with high spatial resolution. This animal model can be used for correlative studies between dispersion of MAP duration and surface estimate of QT dispersion and T wave abnormalities

Multichannel Magnetocardiography: a non\u2013invasive tool for acute and longitudinal cardiac electrophysiologic study of experimental animals in anesthetized and awake conditions

Early identification of potential pro-arrhythmic effects of a new drug has become a goal within the drug development process. Several animal models have been used for the early detection of the so-called \u201cTorsadogenic\u201d risk. In order to fill the gap between animal studies in the preclinical phase of new drugs development and clinical assessment of risk indicators, it would be desirable to use the same methods and parameters. 12-lead ECG is the minimum requirement for adequate assessment of the most used risk indexes (i.e. QT/QTc interval prolongation and of its dispersion), although it has been demonstrated that body surface potential mapping (BSPM) is more sensitive than standard ECG for the evaluation of repolarization inhomogeneity. Whilst BSPM is difficult to be performed routinely in small animals, multi-site magnetocardiographic (MCG) recordings can be an alternative to simplify non-invasive cardiac electrophysiologic mapping. Compared to electric recordings, MCG mapping has several advantages: 1) it is contactless, and adequate also for the study of conscious and unrestrained animals without muscle artifacts; 2) the sensors geometry is fixed, which minimize errors in localization of intracardiac sources and of ventricular repolarization (VR) heterogeneities associated with areas of myocardial injury. Thus MCG is ideal for the study of small experimental animals. Mousses, rats and guinea pigs are the most frequently used to evaluate drug effects on VR in normal conditions and to study models of cardiomyopathy. Among them, the guinea pigs, being non aggressive, can be studied also in the unrestrained conscious state. In our laboratory MCG assessment of cardiac intervals and VR magnetic field distribution has been repeated multiple times, for circadian or long-term longitudinal taking into account possible breed- gender- and age-related differences. Finally a percutaneous method for single-catheter recording of multiple monophasic action potentials (Multi-MAP) from the epicardial surface of intact anesthetized spontaneously beathing rodents has been refined, to validate MCG estimate of VR by comparison with Multi-MAP recordings

Magnetocardiographic estimate of cardiac intervals in guinea pigs. Comparison between conscious and anesthetized conditions

Being a contactless method, multi-site magnetocardiographic (MCG) mapping is ideal for non-invasive study of experimental animals electrophysiology. Since Guinea pigs (GPs) are non aggressive, it is possible to study them also in the unrestrained conscious state Our aim was to assess the feasibility and reliability of MCG mapping, for the measurement of cardiac intervals and quantitative estimate of other MCG VR parameters in the awake (Aw) GP, taking into account possible gender-related differences, and in comparison with MCG recordings of the same animals under anesthesia (An). Methods: 12 adult GPs (6 males and 6 females) were investigated with the same unshielded 36-channel MCG instrumentation used for clinical recordings. Two sets of measurements were performed from each animal, at the age of 14 months (weight: 516.8 \ub1 180 gr): 1) awake, in natural prone posture and 2) under anesthesia (supine). RR, PR, QRS, QTpeak, QTend, JTpeak, JTend and Tpeak-end intervals were measured. MCG imaging and quantitative analysis were automatically obtained as magnetic field maps (MFMs) and with the Equivalent Current Dipole (ECD) inverse solutions. Results: The average interval durations, measured in the two sessions, were RR 250\ub1 50 (Aw) 230\ub150 (An); PR: 60\ub17 (Aw), 58\ub16 (An); QRS: 21.2\ub11.3 (Aw) 223.6\ub12.4 (An); QTpeak: 239\ub124(Aw), 235\ub126 (An); QTend: 270\ub125 (Aw) 280\ub121 (An); JTpeak: 195\ub123 (Aw), 195\ub136 (An); JTend: 225\ub123 (Aw), 239\ub133 (An); Tpeak-end: 30\ub18(Aw), 44\ub110 (An). A statistically significant difference was found only for the Tpeak-end interval. No gender-related differences of VR intervals were observed. Although MFMs were different as a function of the posture, the ECD localization, at the QRSpeak, was properly centered in the heart and coincided within a 3-D uncertainty of less that 10 mm. Conclusions: MCG mapping is reliable for the assessment of cardiac intervals and VR, in the awake as in the anaesthetized GPs. No gender-related differences of VR parameters were observed between the two recording settings. In GP MCG mapping doesn\u2019t require anesthesia and can be repeated multiple times, for circadian or long-term longitudinal pharmacological studie

High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats

AIMS/HYPOTHESIS: Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP). METHODS: Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum. An OGTT was performed every 10 days and histological and immunofluorescence evaluations of the duodenum were obtained at 60 days from the beginning of the diets. Plasma glucose, insulin, GIP and glucagon-like peptide-1 (GLP-1) levels were measured. Immunofluorescence analysis of duodenal sections for pancreatic duodenal homeobox-1 (PDX-1), KI67, GLP-1, GIP and insulin were performed. RESULTS: Compared with chow diet, HFD induced a progressive significant increase of the glucose, insulin and GIP responses to OGTT, whereas GLP-1 circulating levels were reduced over time. After 60 days of HFD, cellular agglomerates of KI67 and PDX-1 positive cells, negative for insulin and GLP-1 but positive for GIP staining, were found inside the duodenal mucosa, and apoptosis was significantly increased. CONCLUSIONS/INTERPRETATION: With the limitation that we could not establish a causal relationship between events, our study shows that HFD stimulates duodenal proliferation of endocrine cells differentiating towards K cells and oversecreting GIP. The progressive increment of GIP levels might represent the stimulus for insulin hypersecretion and insulin resistance

HIGH-DOSE ATORVASTATIN REDUCE OXIDATIVE STRESS OF ISCHEMIA/REPERFUSION INJURY AFTER ISOGENEIC KIDNEY TRANSPLANTATION IN RATS

OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering propertie

N-Acetylcysteine and High-Dose Atorvastatin Reduce Oxidative Stress in an Ischemia-Reperfusion Model in the Rat Kidney

To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury