Targeting liver and adipose tissue in obese mice: Effects of a N-acylethanolamine mixture on insulin resistance and adipocyte reprogramming.

N-acylethanolamines (NAEs) are endogenous lipid-signalling molecules involved in inflammation and energy metabolism. The potential pharmacological effect of NAE association in managing inflammation-based metabolic disorders is unexplored. To date, targeting liver-adipose axis can be considered a therapeutic approach for the treatment of obesity and related dysfunctions. Here, we investigated the metabolic effect of OLALIAMID® (OLA), an olive oil-derived NAE mixture, in limiting liver and adipose tissue (AT) dysfunction of high-fat diet (HFD)-fed mice. OLA reduced body weight and fat mass in obese mice, decreasing insulin resistance (IR), as shown by homeostasis model assessment index, and leptin/adiponectin ratio, a marker of adipocyte dysfunction. OLA improved serum lipid and hepatic profile and the immune/inflammatory pattern of metainflammation. In liver of HFD mice, OLA treatment counteracted glucose and lipid dysmetabolism, restoring insulin signalling (phosphorylation of AKT and AMPK), and reducing mRNAs of key markers of fatty acid accumulation. Furthermore, OLA positively affected AT function deeply altered by HFD by reprogramming of genes involved in thermogenesis of interscapular brown AT (iBAT) and subcutaneous white AT (scWAT), and inducing the beigeing of scWAT. Notably, the NAE mixture reduced inflammation in iBAT and promoted M1-to-M2 macrophage shift in scWAT of obese mice. The tissue and systemic anti-inflammatory effects of OLA and the increased expression of glucose transporter 4 in scWAT contributed to the improvement of gluco-lipid toxicity and insulin sensitivity. In conclusion, we demonstrated that this olive oil-derived NAE mixture is a valid nutritional strategy to counteract IR and obesity acting on liver-AT crosstalk, restoring both hepatic and AT function and metabolism.

Alkalihalobacillus clausii (formerly Bacillus clausii) spores lessen antibiotic-induced intestinal injury and reshape gut microbiota composition in mice.

The antibiotic-induced intestinal injury (AIJ) is associated with diarrhoea and gastrointestinal discomfort. However, the pathological intestinal mechanisms and related side effects associated with antibiotic use/misuse may be counteracted by probiotics. This study aims to evaluate the effect and the protective mechanisms of a probiotic formulation containing Alkalihalobacillus clausii (formerly Bacillus clausii; BC) spores in an experimental model of AIJ. C57/Bl6J mice were orally challenged with a high dose of ceftriaxone for five days along with BC treatment which lasted up to the 15th day. Our results showed the beneficial effect of the probiotic in preserving colonic integrity and limiting tissue inflammation and immune cell infiltration in AIJ mice. BC increased tight junction expression and regulated the unbalanced production of colonic pro- and anti-inflammatory cytokines, converging toward the full resolution of the intestinal damage. These findings were supported by the histological evaluation of the intestinal mucosa, suggesting a potential restoration of mucus production. Notably, BC treatment increased gene transcription of the secretory products responsible for epithelium repair and mucus synthesis and normalized the expression of antimicrobial peptides involved in immune activation. Reconstruction of complex and diverse gut microbiota in antibiotic-induced dysbiosis was recorded upon BC supplementation. Specifically, the expansion of A. clausii, Prevotella rara and Eubacterium ruminatium drove intestinal microbiota rebalance by primarily impacting Bacteroidota members. Taken together, our data indicate that BC administration alleviates AIJ by multiple converging mechanisms leading to restoring gut integrity and homeostasis and reshaping microbiota composition.

Bisphenol A exacerbates anxiety-like behavior and neuroinflammation in prefrontal cortex of adult obese mice.

AIMS: Bisphenol A (BPA) is an endocrine-disrupting chemical inducing several damages such as neurotoxicity, immunotoxicity, and metabolic disorders. Obesity is the main risk factor for the increased occurrence of metabolic alterations as well as mood disorders. Here, we investigated in obese mice the effects of BPA on anxiety-like behavior, associated with neuroinflammation and immune activation. MAIN METHODS: Male C57Bl/6J mice were divided into 4 groups: control group (STD) receiving chow diet and BPA vehicle; STD group treated with BPA (50 µg/kg/die); high-fat diet (HFD) group receiving BPA vehicle; HFD group treated with BPA. BPA treatment started 12 weeks after HFD feeding and lasted 3 weeks. KEY FINDINGS: The open field and elevated plus-maze tests showed in HFD + BPA group the worsening of HFD-induced anxiety-like behavior. The anxiogenic effects of BPA also emerged from hyperactivation of the hypothalamus-pituitary-adrenal gland axis, determined by the increased transcription of Crh and its receptor in the prefrontal cortex (PFC). Furthermore, BPA activated NLRP3 inflammasome and exacerbated the neuroinflammation induced by HFD, increasing IL-1ß, TNF-α and monocyte chemoattractant protein (MCP)-1 in PFC. Furthermore, it induced inflammation and monocyte recruitment in hypothalamus and amygdala. Contextually, BPA significantly amplified the immune activation caused by lipid overload as evidenced by the increased expression of TLR-4 and MCP-1 in the PFC and triggered mastocytosis in the hypothalamus rather than STD mice. SIGNIFICANCE: All these data show that sub-chronic BPA exposure represents an additional risk factor for mood disorders strictly related to obesity, enhancing neuroinflammation and immune activation triggered by HFD feeding.

The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial.

OBJECTIVE: To evaluate the ability of oral supplements with immune-stimulating molecules (Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C) to reduce the inflammation of the upper airway tract and improve the outcome of otitis media with effusion (OME) in children. PATIENTS AND METHODS: Randomized controlled trial. One-hundred ninety-eight children (CI 95%: 12-96 months) were divided into four groups. Group 1 (48 subjects) received 10 ml of oral supplements (OS) with immune-stimulating molecules for three months (20 days consecutively, then 10 days of suspension - the therapeutic scheme was repeated three times); Group 2 (54 children) underwent treatment with 10 ml of OS for 90 consecutive days; Group 3 (48 subjects) received 15 ml of OS for 45 consecutive days; a control group (48 children) underwent the standard treatment for rhinitis and OME. Outcome measures included otoscopy, tympanometry, fibroendoscopy, and the pure tone audiometry (PTA) at T0 (before treatment), T1 (45 days after treatment), and T2 (90 days after treatment). RESULTS: All children treated with OS showed a reduction of Upper Airway Infection (UAI) episodes and OME compared to the control group independent of the administration method and posology. The three groups treated with OS showed statistically significant differences between T0 and T2 for otoscopy, tympanometry, fibroendoscopy, and PTA. In Group 2, the otoscopy and the tympanometry scores improved at T1. Group 2 and 3 had better PTA results than Group 1. CONCLUSIONS: OS with immune-stimulating molecules should be considered as a supporting therapy in children affected by recurrent episodes of UAI associated with OME due to their capacity to improve the immune response and reduce the inflammatory phenomena. OS can improve the fibroendoscopic findings by restoring middle ear ventilation, in addition to their ability to reduce inflammation in the middle ear.

Pre-treatment with Melamil Tripto® induces sleep in children undergoing Auditory Brain Response (ABR) testing.

OBJECTIVES: Previous studies have shown that tryptophan and vitamin B6 used in conjunction with melatonin induce sleep more effectively than melatonin alone. This study aims at evaluating the efficacy of different dosages and timings of administration of a solution containing melatonin, tryptophan, and vitamin B6 for inducing sleep in children undergoing ABR testing. METHODS: 294 children scheduled for Auditory Brain Response (ABR) evaluation were administered a solution containing melatonin, tryptophan, and vitamin B6 to induce sleep before the exam. Two different administration timings (pre-treatment and single shot treatment) and three dosages (0.5 ml in pre-treatment, 1.5 ml in pre-treatment, and 3 ml in single shot) were tested. The following parameters were evaluated: time needed for the subject to fall asleep before ABR testing, subject sl'eep features during ABR testing (quality, stability, duration), recorded ABR quality (including presence of abnormalities in amplitude and latency), subject waking up modality, and time needed for the subject to wake up at the end of the ABR exam. RESULTS: Quality of ABR signals was similar across treatments, and subjects responded in a similar manner in terms of time needed to wake-up and wake-up modality. However, pretreatment with the 1.5 ml dose induced sleep faster than the two other dosages, and the length of the induced sleep was longer than that induced by pre-treatment with 0.5 ml. In general, the pre-treatment with 1.5 ml led to a shorter ABR exam, because reduces the time for inducing sleep, allows a long sleeping phase with a good quality, without variation in the wakening up times. CONCLUSIONS: Melamil Tripto® is an alternative to sedative drugs for inducing sleep in pediatric subjects undergoing ABR testing. A pre-medication with 1.5 ml of MT 1 week before ABR testing further improves the strength of the solution.

Intestinal derotation in emergency surgery.

Intestinal derotation (ID) is a rarely used surgical technique which allows elegant and effective surgical access to the superior mesenteric axis and third and fourth portion of the duodenum. ID proves an extremely useful technique especially in the emergency setting when access to the "surgical soul" is needed. To master this technique the surgeon has to become familiar with the anatomical landmarks of that area along with the embryological background.

Potentiation of phosphodiesterase inhibitor antithrombotic activity with alpha-2 adrenergic blockade.

The antithrombotic activity of pelrinone, a phosphodiesterase III inhibitor was examined in a canine model of coronary thrombosis that uses electrical current to injure the coronary endothelium. Ninety percent of vehicle treated animals developed complete coronary occlusion and thrombus mass was 32.0 +/- 5.8 mg. In a group of animals treated with zomepirac, 10 mg/kg i.v., included as a positive control, thrombus mass was decreased to 10.3 +/- 3.3 mg and incidence of occlusion was reduced to 37.5%. Pelrinone, 5.0 mg/kg i.v. decreased the incidence of occlusion to 50%, thrombus mass to 21.3 +/- 8.3 mg and inhibited platelet aggregation to collagen, ADP and arachidonic acid by 80%, 54% and 87% of baseline, respectively. When yohimbine, an alpha 2-adrenergic antagonist, was co-administered (2.0 mg/kg at the beginning of the experiment +0.5 mg/kg halfway through the experiment) with the same dose of pelrinone, thrombus mass was decreased to 1.0 +/- 0.5 mg and none of the animals developed coronary occlusion. Yohimbine administration by itself at 2.0-3.0 mg/kg showed no evidence of antithrombotic activity (thrombus mass = 32.8 +/- 8.0 mg, incidence of occlusion = 100%). This dose of yohimbine inhibited significantly ADP-induced aggregation in the presence of epinephrine. These results demonstrate that, even though this dose of pelrinone elicited near maximal inhibition of platelet aggregation, the concurrent administration of an alpha 2-adrenergic antagonist was able to potentiate markedly the phosphodiesterase inhibitor antithrombotic activity.

[Cancer of the gastric stump after resection for ulcer]. / Il cancro del moncone gastrico nei resecati per ulcera

Fourteen cases of primary cancer of the gastric stump as a long-term sequel to resection for ulcer are presented. Surgery was undertaken in all cases, though radical intervention was only possible in 6. Questions of diagnosis and surgical tactics associated with this type of neoplasia are discussed. It is felt that early ascertainment could be aided by fibrogastroscopic controls carried out on a large scale at the time of the symptomatological overture. The possibility of preventive examination is also mooted.