Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease.

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study.

Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF).

Methods: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT.

Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation.

The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks.

Angiotensin II Modulates Calcium/Phosphate Excretion in Experimental Model of Hypertension: Focus on Bone.

A link between hypertension and long-term bone health has been suggested. The aim of this study was to investigate the effects of chronic angiotensin II administration on urinary calcium/phosphate excretion, bone mineral density, bone remodeling and osteoblast population in a well-established experimental model of hypertension, in the absence of possible confounding factors that could affect bone metabolism. Male Sprague-Dawley rats, divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis, = 8); (b) Ang II+losartan (Los, 50 mg/kg/day, , = 6); (c) control group (physiological saline, sub cutis, = 9); and (d) control+losartan ( = 6) were treated for four weeks.

Angiotensin Type 2 and Mas Receptor Activation Prevents Myocardial Fibrosis and Hypertrophy through the Reduction of Inflammatory Cell Infiltration and Local Sympathetic Activity in Angiotensin II-Dependent Hypertension.

Compound 21 (C21), an AT2 receptor agonist, and Angiotensin 1-7 (Ang 1-7), through Mas receptor, play an important role in the modulation of the protective arm of the renin-angiotensin system. The aim of this study was to investigate in an experimental model of angiotensin II-dependent hypertension whether the activation of the potentially protective arm of the renin-angiotensin system, through AT2 or Mas receptor stimulation, counteracts the onset of myocardial fibrosis and hypertrophy, and whether these effects are mediated by inflammatory mechanism and/or sympathetic activation. Sprague Dawley rats ( = 67) were treated for 1 ( = 25) and 4 ( = 42) weeks and divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis); (b) Ang II+Compound 21 (C21, 0.

Sodium-glucose cotransporter 2 inhibition prevents renal fibrosis in cyclosporine nephropathy.

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes.

Methods: Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period.

Head down tilt 15° in experimental intracerebral hemorrhage: a randomized noninferiority safety trial.

Background And Purpose: Head down tilt 15° (HDT15°), applied before recanalization, increases collateral flow and improves outcome in experimental ischemic stroke. For its simplicity and low cost, HDT15° holds considerable potential to be developed as an emergency treatment of acute stroke in the prehospital setting, where hemorrhagic stroke is the major mimic of ischemic stroke. In this study, we assessed safety of HDT15° in the acute phase of experimental intracerebral hemorrhage.

Resting Whole Body Energy Metabolism in Class 3 Obesity; from Preserved Insulin Sensitivity to Overt Type 2 Diabetes.

Context: Insulin resistance and diabetes may influence separately or in combination whole body energy metabolism.

Objective: To assess the impact of insulin resistance and/or overt type 2 diabetes on resting energy expenditure (REE) in class 3 obese individuals.

Design And Setting: Retrospective, cross-sectional analysis of a set of data about individuals attending the outpatients service of a single center of bariatric surgery between January 2015 and December 2017.

Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy.

Context: Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism.

Objective: To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE).

Design: Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center from January 2013 to July 2019.

Potential of calcium nitrate to mitigate the aluminum toxicity in Phaseolus vulgaris: effects on morphoanatomical traits, mineral nutrition and photosynthesis.

Common bean (Phaseolus vulgaris) cultivation occurs mainly in regions with acidic soils, where high aluminum (Al) concentration is a major constraint to crop production. In this study, we evaluated tolerance and sensitivity traits to Al exposure and calcium (Ca) deficiency in bean plants, and determined the efficiency of Ca to mitigate the toxic Al effects. Two bean cultivars (BRS Estilo and Campos Gerais) were grown in three soil conditions: (I) soil liming with calcium hydroxide Ca(OH) and Al unavailable (-Al+Ca); (II) fertilized soil with calcium nitrate [Ca(NO)·4HO] and Al available (+Al+Ca); and (III) soil without Ca addition and Al available (+Al-Ca).

Renal Anti-Fibrotic Effect of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension.

Background: Clinical trials have shown that empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, promotes nephroprotective effects in diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is not known whether the renal beneficial action is present even in non-diabetic kidney disease. The aim of this study was to evaluate the effect of Empa administration on the development of renal fibrosis in an experimental model of angiotensin II (Ang II)-dependent hypertension.

Fasting Whole-Body Energy Homeostasis and Hepatic Energy Metabolism in Nondiabetic Humans with Fatty Liver.

Background: Fatty liver is believed to be sustained by a higher than normal adipose-derived NEFA flux to the liver. Also, hepatic energy metabolism may be a rate-limiting step of intrahepatic fat (IHF) accumulation.

Aims: To assess whole-body energy metabolism and hepatic high-energy phosphates (HEPs) in individuals with fatty liver.

Activation of angiotensin type 2 (AT2) receptors prevents myocardial hypertrophy in Zucker diabetic fatty rats.

Aims: Compound 21 (C21), selective AT2 receptor agonist, has cardioprotective effects in experimental models of hypertension and myocardial infarction. The aims of the study was to evaluate the effect of C21, losartan, or both in Zucker diabetic fatty (ZDF) rats (type 2 diabetes) on (1) the prevention of myocardial hypertrophy; (2) myocardial expression of phosphatase and tensin homolog (PTEN), a target gene of miR-30a-3p, involved in myocardial remodelling.

Methods: Experiments were performed in ZDF (n = 33) and in control Lean (8) rats.

NAFLD/NASH in patients with type 2 diabetes and related treatment options.

Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.

Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood pressure independent effect.

Compound 21 (C21), selective agonist of angiotensin type-2 (AT-2) receptors, shows anti-inflammatory effects in experimental models of hypertension and nephroprotection in diabetes. The aim of the present study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague-Dawley rats.

Different regulation of miR-29a-3p in glomeruli and tubules in an experimental model of angiotensin II-dependent hypertension: potential role in renal fibrosis.

The aim of this study was to evaluate the role of the angiotensin II (Ang II) induced-differential miRNA expression in renal glomerular and tubulo-interstitial fibrosis in an experimental model of Ang II-dependent hypertension. To clarify this issue, Sprague Dawley rats were treated with Ang II (200 ng/kg per minute, n = 15) or physiological saline (n = 14) for 4 weeks. Systolic blood pressure and albuminuria were measured every 2 weeks.

Brachial and central blood pressure in HIV-infected subjects.

HIV infected subjects present an unfavorable cardiovascular (CV) risk profile that is determined by the infection itself, highly active anti-retroviral therapy (HAART) and other factors, such as chronic kidney disease (CKD). Information is scant and contradictory on whether these factors are associated with arterial stiffness and blood pressure (BP) alteration. Our study aimed to evaluate those parameters in HIV-positive subjects both with and without HAART and with and without CKD, which was defined as the presence of microalbuminuria with a normal glomerular filtration rate.

Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats.

The aim of this study was to evaluate the effect of compound 21 (C21), a selective AT2 receptor agonist, on diabetic nephropathy and the potential additive effect of C21, when associated with losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The experiments lasted 15 wk (from 5 to 20 wk of age) and were performed in 40 ZDF rats and 12 control lean rats. ZDF rats were divided into 4 groups: 1) 9 rats were treated with losartan; 2) 10 rats were treated with C21; 3) 9 rats were treated with losartan plus C21; and 4) 12 rats were maintained without any treatment.

Urinary exosomes and diabetic nephropathy: a proteomic approach.

Urinary exosomes (UE) are nanovesicles released by every epithelial cell facing the urinary space and they are considered a promising source of molecular markers for renal dysfunction and structural injury. Exosomal proteomics has emerged as a powerful tool for understanding the molecular composition of exosomes and has potential to accelerate biomarker discovery. We employed this strategy in the study of diabetic nephropathy (DN) and the consequent end stage renal disease, which represent the dramatic evolution of diabetes, often leading the patients to dialysis or kidney transplantation.

Renal antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.

Background And Aim: Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis.

NF-κB mediated miR-26a regulation in cardiac fibrosis.

Micro-RNAs (miRNAs) are a class of small non-coding RNAs, recently emerged as a post-transcriptional regulator having a key role in various cardiac pathologies. Among them, cardiac fibrosis that occurs as a result from an imbalance of extracellular matrix proteins turnover and is a highly debilitating process that eventually lead to organ dysfunction. An emerging theme on is that miRNAs participate in feedback loop with transcription factors that regulate their transcription.

The combined effect of ADL impairment and delay in time from fracture to surgery on 12-month mortality: an observational study in orthogeriatric patients.

Background: Delayed surgery (ie, >48 hours from arrival in hospital) and pre-fracture disability are thought to be long-term risk factors for mortality in patients with hip fracture (HF). However, the combined effect on mortality of these two conditions has not been satisfactorily assessed in previous studies.

Objective: To assess the combined effect of pre-fracture disability and delayed surgery on 12-month mortality in a population of elderly patients after HF surgical treatment.