Indicaxanthin from Opuntia ficus-indica fruit ameliorates glucose dysmetabolism and counteracts insulin resistance in high-fat-diet-fed mice

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between in-flammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remark-able, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility.

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in -PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if -PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a -PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a traceamine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous -PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of -PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through -PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus

5.16 Left Ventricular Geometry In Chronic Kidney Disease

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NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet

Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT1R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance

Synchronous Bilateral Paget's Disease of the Nipple Associated with Bilateral Breast Carcinoma

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Gastro-intestinal symptoms as clinical manifestation of peritoneal and retroperitoneal spread of an invasive lobular breast cancer: report of a case and review of the literature

BACKGROUND: Distant spread from breast cancer is commonly found in bones, lungs, liver and central nervous system. Metastatic involvement of peritoneum and retroperitoneum is unusual and unexpected. CASE PRESENTATION: We report the case of a 67 year-old-woman who presented with gastrointestinal symptoms which revealed to be the clinical manifestations of peritoneal and retroperitoneal metastatic spread of an invasive lobular breast cancer diagnosed 15 years before. CONCLUSION: To the best of our knowledge, the case presented is the third one reported in literature showing a wide peritoneal and extraperitoneal diffusion of an invasive lobular breast cancer. The long and complex diagnostic work up which led us to the diagnosis is illustrated, with particular emphasis on the multidisciplinary approach, which is mandatory to obtain such a result in these cases. Awareness of such a condition by clinicians is mandatory in order to make an early diagnosis and start a prompt and correct therapeutic approach

Ruolo della timectomia nel trattamento della miastenia gravis: considerazioni e casistica personale

L’effetto terapeutico della timectomia sul decorso clinico della miastemia gravis è ancora quanto mai controverso. Infatti, mentre la chirurgia è ormai universalmente accettata per i timomi, il suo ruolo è ancora discutibile in pazienti con miastenia gravis. La via chirurgica di elezione per la timectomia totale è rappre - sentata dalla sternotomia mediana. Altre metodologie chirurgiche includono l’accesso cervicale e la sternotomia parziale. Queste tecni - che, seppure con alterne fortune, hanno mostrato risultati eccellenti nella exeresi del timo. Più recentemente la timectomia toracoscopica video-assistita è stata proposta come una tecnica meno invasiva e parimenti efficace per l’asportazione di quest’organo ed il trattamento della miastenia gravis. Scopo del presente lavoro è quello di riferire l’esperienza degli Autori in tema di timectomia, analizzando i dati riportati dalla lette - ratura internazionale sulla mortalità operatoria, le eventuali compli - canze e i risultati estetici delle diverse tipologie di accesso chirurgico

Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice

The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD

Granular Cell Tumor of the Breast: Clinical Presentation, Pathological Diagnosis and Treatment

Introduction: Granular cell tumor is a rare neoplasm of soft tissue and only in 1% of cases, it can shows a malignant behaviour. It is presumed to be a tumor originating from perineural or putative Schwann cells of peripheral nerves. Materials and Methods: We reviewed five patients affected by Granular cell tumor of the breast treated between January 2011 and January 2021 at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome, Italy. Results: All of the granular cell tumors presented as solitary, painless and firm lump, highly suggestive of malignancy. The radiological findings were heterogeneous and non-specific. All lesions presented as masses, more clearly evident on ultrasound as hypoechoic lesions, with irregular shape, blurred contours and borderline features. The tumors were composed of large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei, being immunohistochemically positive for S100, Vimentin (with variable staining), CD56; negative for HMB45, MelanA, AE1/AE3, EMA, and Desmin. Conclusion: Granular cell tumor is a rare, usually benign breast disease that can have very similar characteristics to breast cancer both clinically and radiologically. Treatment of choice consists in wide resection or lumpectomy with margin assessment (no ink on tumor)