Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients

Angiotensin-(1–7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy

ACE (angiotensin-converting enzyme) 2 is expressed in the heart and kidney and metabolizes Ang (angiotensin) II to Ang-(1–7) a peptide that acts via the Ang-(1–7) or mas receptor. The aim of the present study was to assess the effect of Ang-(1–7) on blood pressure and cardiac remodelling in a rat model of renal mass ablation. Male SD (Sprague–Dawley) rats underwent STNx (subtotal nephrectomy) and were treated for 10 days with vehicle, the ACE inhibitor ramipril (oral 1 mg·kg−1 of body weight·day−1) or Ang-(1–7) (subcutaneous 24 μg·kg−1 of body weight·h−1) (all n = 15 per group). A control group (n = 10) of sham-operated rats were also studied. STNx rats were hypertensive (P<0.01) with renal impairment (P<0.001), cardiac hypertrophy (P<0.001) and fibrosis (P<0.05), and increased cardiac ACE (P<0.001) and ACE2 activity (P<0.05). Ramipril reduced blood pressure (P<0.01), improved cardiac hypertrophy (P<0.001) and inhibited cardiac ACE (P<0.001). By contrast, Ang-(1–7) infusion in STNx was associated with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05) and fibrosis (P<0.01). Ang-(1–7) infusion also increased cardiac ACE activity (P<0.001) and reduced cardiac ACE2 activity (P<0.05) compared with STNx-vehicle rats. Our results add to the increasing evidence that Ang-(1–7) may have deleterious cardiovascular effects in kidney failure and highlight the need for further in vivo studies of the ACE2/Ang-(1–7)/mas receptor axis in kidney disease

Recent advances in metal-, organo-, and biocatalyzed one-pot tandem reactions under environmentally responsible conditions

Because of their handedness and wide scope, transitionmetal-, organo-, and biocatalyzed tandem processes have become routine and highly sought-after methodologies because they dramatically increase synthetic efficiency, while decreasing the number of laboratory operations, the quantities of chemicals and solvents used, producing in a simpler way highly complex organic molecules with the desired selectivity. In this current opinion, recent examples of the use of metal-, organo-, and biocatalyzed tandem processes run under environmentally responsible conditions (e.g., use of water, biobased solvents, or without additional solvents) are showcased, highlighting practical and valuable aspects

Reazioni Mediate e Catalizzate Da Metalli In Solventi Non Convenzionali: Aspetti Sintetici e Meccanicistici

Green chemistry integrates environmentally safe and sustainable technologies for chemical research and production. Classical synthetic protocols, even with widespread applicability, have various drawbacks due to the use of harsh conditions, long reaction times, and the generation of large amounts of waste. Over the past few years, our research group has been focusing on the development of methodologies with a low ecological footprint using the so-called Deep Eutectic Solvents (DESs) and water as environmentally responsible reaction media and catalysts, thereby reshaping several organic transformations, which are traditionally carried out using toxic and often harmful petroleum-based volatile organic compounds. In this context, metal-mediated and metal-catalysed organic reactions have been successfully accomplished in the aforementioned reaction media under mild conditions and under airLa chimica verde comprende tecnologie sostenibili e sicure per l’ambiente, la ricerca e la produzione chimica industriale. I protocolli sintetici classici, presentano vari inconvenienti dovuti all’uso di condizioni di reazione drastiche, tempi lunghi e produzione di grandi quantità di rifiuti. Negli ultimi anni, il nostro gruppo di ricerca si è concentrato sullo sviluppo di metodologie a basso impatto ambientale, basate sull’utilizzo di acqua o miscele eutettiche a basso punto di fusione sia come mezzi di reazione che come catalizzatori. In questo contesto, reazioni organiche mediate e catalizzate da metalli sono state realizzate con successo nei suddetti mezzi in condizioni blande, all’aria e in tempi brev

Directed ortho-metalation–nucleophilic acyl substitution strategies in deep eutectic solvents: the organolithium base dictates the chemoselectivity

Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki-Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents

Advances in Deep Eutectic Solvents and Water: Applications in Metal- and Biocatalyzed Processes, in the Synthesis of APIs, and other Biologically Active Compounds

Owing to a growing awareness towards environmental impact, the search for “greener”, safer, and cost-effective solvents able to replace petroleum-derived solvents has never been greater today. In this context, the use of environmentally responsible solvents like water and the so-called Deep Eutectic Solvents (DESs), constructed from bio-based compounds, has recently experienced important growth in several fields of sciences. This short review highlights the key features of the chemistry of water and (hydrated) DESs when applied to metal- and biocatalyzed transformations as well as to the synthesis of Active Pharmaceutical Ingredients (APIs) and other biologically relevant compounds by providing, through discussion of all relevant literature over the past five years, a comparison of the outcomes of the reactions when carried out in one or the other solvent