The anti-inflammatory and immunological properties of SGLT-2 inhibitors.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic oral drugs that act on proximal renal tubules promoting renal glucose excretion. Although SGLT-2i belong to the class of hypoglycemic agents, in the last years great interest has emerged in studying their pleiotropic effects, beyond their ability to lower glucose levels. PURPOSE: In this review we are describing the anti-inflammatory and immunological properties of SGLT-2i; furthermore, we are addressing how the mechanisms associated with the aforementioned anti-inflammatory properties may contribute to the beneficial effects of SGLT-2i in diabetes. METHODS: A systematic search was undertaken for studies related the properties of SGLT-2i in reducing the inflammatory milieu of acute and chronic disease by acting on the immune system, independently by glycemia. RESULTS: Recently, some data described the anti-inflammatory and immunological properties of SGLT-2 in both pre-clinical and clinical studies. Numerous data confirmed the cardio- and -renal protective effects of SGLT-2i in patients with heart failure and kidney diseases, with or without diabetes. CONCLUSIONS: SGLT-2i are promising drugs with anti-inflammatory and immunological properties. Despite the mechanism of action of SGLT-2i is not fully understood, these drugs demonstrated anti-inflammatory effects, which may help in keeping under control the variety of complications associated with diabetes.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

The structured assessment of depression in brain-damaged individuals: translation and validation study of the Italian version.

The aim of this study was to translate the structured assessment of depression in brain-damaged individuals (SADBD) questionnaire into the Italian language, validate, and test reliability and validity of the Italian version. Consecutive patients with stroke were screened in the Department of Neurology, Avogadro University in Novara and the Department of Neurorehabilitation, Maugeri Foundation, Veruno, Italy. Thirty patients were included in the study. The internal consistency ranged between 0.78 and 0.87. The intra-rater test-retest reliability was 0.93 for BDIderived items and 0.82 for HRSD-derived items; while the inter-rater test-retest reliability was 0.94 for BDI-derived items and 0.93 for HRSD-derived items. Correlation between the SADBD diagnosis made by the physician and the nurse was 0.51; correlation between caregiver and physician diagnosis was 0.60. The Italian version of the SADBD was demonstrated to be acceptable, reliable and a valid measure of depression in patients with stroke.

Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results.

Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases. The purpose of this study was to examine the effects of supplementation on exercise performance and maximal voluntary isometric muscular contraction (MVIC) in Amyotrophic Lateral Sclerosis (ALS) patients. We report the results obtained in 28 patients with probable/definite ALS. In each patient we acquired the dynamometric measurement of MVIC in 10 muscle groups of upper and lower limbs and a measure of fatigue by means of an high-intensity intermittent protocol in elbow flexors and knee extensors muscles. All patients completed the protocols at the baseline and after supplementation of 20 g per day for 7 days and after supplementation of 3 g per day for 3 and 6 months. MVIC increased after 7 days of supplementation in 20 patients (70%) in knee extensors and in 15 (53%) of them also in elbow flexors. A statistically significant difference between pre and post-treatment mean values of MVIC was found both in elbow flexors (P<0.05) and knee extensors (p<0.04). The analysis of the slopes of fatigue test showed a statistically significant improvement after 7 days of supplementation in 11 patients (39%) in elbow flexors and in 9 patients (32%) also in knee extensors muscles. During the 6-month follow-up period all the examined parameters showed a linear progressive decline. In conclusion, our preliminary results have demonstrated that supplementation temporary increases maximal isometric power in ALS patients so it may be of potential benefit in situations such as high intensity activity and it can be proposed as a symptomatic treatment.

Changes in expression of the oligosaccharides in the human fetal skin.

Lectin histochemistry was used to investigate the glycoconjugate saccharidic moieties in the skin of human fetuses ranging in age from the 8th to the 13th week of gestation. For this purpose, seven HRP-conjugated lectins were employed (Con A, WGA, PNA, DBA, SBA, UEAI and LTA). The distribution and changes of the sugar residues of glycoconjugates at the level of the various layers of the fetal epidermis, as well of the underlying mesenchyme were studied. We have shown that UEAI reactivity is a characteristic finding of the cells of the intermediate layer at the 11th and 12th week of gestation. LTA reactivity was detected only at the free border of the peridermal cells from the 10th to the 13th week of gestation. We demonstrated the presence of PNA binding sites at both the basal and peridermal cells from the 8th week of gestation, whereas other authors have stated that the appearance of PNA reactivity coincides with the onset of fetal skin stratification (11th-12th week of gestation). Moreover, some typical features in lectin reactivity at the level of the mesenchymal cells and fibres have been pointed out.

Unexplained bilateral occipital calcification and reduced vision.

An eight year-old girl, investigated because of convulsions, was found to have isolated bilateral presumably cortical and subcortical calcification, reduced visual acuity and prolonged visual evoked response latencies. There were no clinical manifestations of a phakomatosis.