Imbalance of Myoinositol and D-Chiro-Inositol in Saliva of Children With Type-1 Diabetes Mellitus: A Cross-Sectional Study.

Objective: Earlier work suggests Myoinositol (MI) and D-chiro- inositol (DCI) imbalance in urine and plasma of diabetic patients, and their potential for monitoring insulin resistance. This study aimed to assess levels of Myoinositol (MI) and D-chiro- inositol (DCI) in saliva of children with type 1 diabetes mellitus (DM-1) and controls, to verify if concentrations of MI and DCI are similarly altered in saliva, exploring their potential for monitoring DM-1.

Design, Patients And Measurements: This cross-sectional clinical study enroled 45 patients (DM-1, n = 25; Controls, n = 20).

Pharmacological evaluation of a new nanoformulation in the erectile tissue of rabbits and humans.

The failure of achieving a penile erection for satisfactory sexual intercourse is known as erectile dysfunction (ED). The primary mediator for penile erection is nitric oxide (NO). ED is often associated with endothelial/nitrergic dysfunction characterized by a reduction of the bioavailability of NO.

Anti-bacterial, anti-biofilm and synergistic effects of phenazine-based ruthenium(II) complexes.

Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on -[Ru(bpy)(dppz)(SO)(NO)](PF) (PR02, bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-:2',3'-]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties.

Rutin ameliorates nitrergic and endothelial dysfunction on vessels and corpora cavernosa of diabetic animals.

Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop autonomic neuropathies. Increased oxidative stress has a major role in the development of both nitrergic and endothelial dysfunction.

Nitroprusside─Expanding the Potential Use of an Old Drug Using Nanoparticles.

For more than 70 years, sodium nitroprusside (SNP) has been used to treat severe hypertension in hospital emergency settings. During this time, a few other clinical uses have also emerged such as in the treatment of acute heart failure as well as improving mitral incompetence and in the intra- and perioperative management during heart surgery. This drug functions by releasing nitric oxide (NO), which modulates several biological processes with many potential therapeutic applications.

Diterpenoids from Leaves of Cultivated Plectranthus ornatus.

Two new diterpenoid derivatives 7,12,17-triacetoxy-619-dihydroxy-13,16-spirocicloabiet-8-ene-11,14-dione ( 1: ) and 6-acetoxy-3,7,12-trihydroxy-13,16-spirocicloabiet-8-ene-11,14-dione ( 2: ) along with 11 ( 3: - 13: ) miscellaneous compounds were isolated from the leaves of Codd. Their structures were elucidated by spectroscopic analysis and gauge independent atomic orbitals C NMR calculations. The isolated compounds were screened for their effects on intestinal motility using guinea-pig ileum and duodenum and by their cytotoxicity against 4 human cancer cell lines (HCT-116, SF-295, PC-3, and HL-60).

Pentacyanoferrate(II) complex of pyridine-4- and pyrazine-2-hydroxamic acid as source of HNO: investigation of anti-tubercular and vasodilation activities.

A pharmacophore design approach, based on the coordination chemistry of an intimate molecular hybrid of active metabolites of pro-drugs, known to release active species upon enzymatic oxidative activation, is devised. This is exemplified by combining two anti-mycobacterial drugs: pyrazinamide (first line) and delamanid (third line) whose active metabolites are pyrazinoic acid (PyzCOOH) and likely nitroxyl (HNO (or NO)), respectively. Aiming to generate those active species, a hybrid compound was envisaged by coordination of pyrazine-2-hydroxamic acid (PyzCONHOH) with a Na[Fe(CN)] moiety.

A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity.

Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors.

Renal protective effect of pinitol in experimental diabetes.

Pinitol is a natural antidiabetic agent shown to prevent or ameliorate metabolic and overall vascular and neural function. In the present study we have evaluated the potential benefits of pinitol on renal function of streptozotocin (STZ)-induced diabetic rats. Both euglycemic or 8-week or 16-week diabetic rats were treated with either saline (1 ml/kg/12h; p.

Antihypertensive potential of cis-[Ru(bpy)(ImN)(NO)], a ruthenium-based nitric oxide donor.

The aim of this study was to investigate the antihypertensive properties of cis-[Ru(bpy)ImN(NO)] (FOR0811) in normotensive and in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Vasorelaxant effects were analyzed by performing concentration response curve to FOR0811 in rat aortic rings in the absence or presence of 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ), L-cysteine or hydroxocobalamin. Normotensive and L-NAME-hypertensive rats were treated with FOR0811 and the effects in blood pressure and heart rate variability in the frequency domain (HRV) were followed.

Effect of indole alkaloids from roots of Rauvolfia ligustrina in the noradrenergic neurotransmission.

The new glucosyl sarpagan alkaloid designated as 21(R*)-(O-β-glucosyl)-hydroxy-sarpagan-17-oic acid, along with eleven known alkaloids were isolated from a soluble alkaloidal fraction from the ethanol extract of Rauvolfia ligustrina. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiment, GIAO C NMR calculations, and comparison with literature data. All the isolated alkaloids were screened by their neuroinhibitory effects using the electrically stimulated mice vas deferens bioassay.

Early consumption of high-fat diet worsens renal damage in spontaneously hypertensive rats in adulthood.

The association between hypertension and obesity has been shown to be an important cause of kidney disease. We aimed to investigate the impact of a high-fat diet (HFD) administered in spontaneously hypertensive rats (SHR) after weaning in renal morphology and functional parameters. Male post-weaned SHR were divided into two groups: standard control diet (CD) (3% lipids; n = 8) or HFD (30% lipids; n = 8) during 8 weeks.

PKB is a central molecule in the modulation of Na-ATPase activity by albumin in renal proximal tubule cells.

Evidence points to a possible role of tubular sodium reabsorption in worsening renal injury. Proximal tubule (PT) albumin overload is a critical process in the development of tubule-interstitial injury (TII), and consequently in progression of renal disease. We studied the possible correlation between changes in albumin concentration in the lumen of PT with modification of Na-ATPase activity.

Post-weaning Exposure to High-Fat Diet Induces Kidney Lipid Accumulation and Function Impairment in Adult Rats.

We investigated the kidney morphofunctional consequences of high-fat diet intake since post-weaning in adult rats. Male Wistar rats were divided into two groups: ND (normal diet; = 10) and HD (high-fat diet; = 10). The high-fat diet was introduced post-weaned and animals were followed for 8 weeks.

Incorporation of Nitroprusside on Silica Nanoparticles-A Strategy for Safer Use of This NO Donor in Therapy.

Silica-based nanoparticles have been developed as powerful platforms for drug delivery and might also prevent undesired side effects of drugs. Here, a fast method to synthesize positively charged mesoporous silica nanoparticles (ζ = 20 ± 0.5 mV, surface area = 678 m g, and 2.

In vitro and in vivo leishmanicidal activity of a ruthenium nitrosyl complex against Leishmania (Viannia) braziliensis.

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. There are many complications presented by the current treatment, as high toxicity, high cost and parasite resistance, making the development of new therapeutic agents indispensable. The present study aims to evaluate the leishmanicidal potential of ruthenium nitrosyl complex cis-[Ru(bpy)(SO)(NO)](PF) against Leishmania (Viannia) braziliensis.

Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model.

Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using and methods, being compared with a normal control group. We investigated in model of the role of the renin Angiotensin system (RAS) in the kidney.

Effect of co-administration of two different phosphodiesterase inhibitors and a β-adrenoceptor agonist in an experimental model of detrusor overactivity.

The purpose of this study was to evaluate in vitro the effect of the combination of BRL 37344 (ß-adrenoceptor agonist) with tadalafil (phosphodiesterase type 5 inhibitor) or rolipram (phosphodiesterase type 4 inhibitor) in an experimental model of detrusor overactivity. The experiments were carried out in two phases using bladder strips of mice. In the first phase, on the top of 40 mM potassium-induced contraction, strips isolated from control mice were exposed to increasing concentrations of each study drug.

Thiocarbonyl-bound metallonitrosyl complexes with visible-light induced DNA cleavage and promising vasodilation activity.

Nitric oxide has been involved in many key biological processes such as vasodilation, platelet aggregation, apoptosis, memory function, and this has drawn attention to the development of exogenous NO donors. Metallonitrosyl complexes are an important class of these compounds. Here, two new ruthenium nitrosyl complexes containing a thiocarbonyl ligand, with the formula cis-[Ru(phen)(L)(NO)](PF) (phen = phenantroline, L = thiourea or thiobenzamide), were synthesized and characterized by electronic spectroscopy, FTIR, NMR mass spectrometry and voltammetric techniques.

Neuroinhibitory meroterpenoid compounds from Cordia oncocalyx.

Five new meroterpenoid compounds designed as rel-10β,11β-epoxy-2,11-dimethoxy-8α-hydroxy-8aβ-methyl-5α,6,7,8,8a,9,10,10aβ-octahydro-1,4-anthracendione (1), rel-10β,11β-epoxy-8α,5-dihydroxy-2-methoxy-8aβ-methyl-5,6,7,8,8a,9,10,10aβ-octahydro -1.4-anthracendione (2), rel-1,4,8α-trihydroxy-5-furanyl-2-methoxy-8aβ-methyl-6,7,8, 8a,9,10-hexahydro-10-anthracenone (3), rel-10α,11α-epoxy-8α,11β-dihydroxy-8aβ-methyl-5β,6,7,8,8a,9,10,10aβ-octahydro-1,4-anthracenediol (4) and rel-1,4,8α-trihydroxy-5-carboxyethyl-2-methoxy-8aβ-methyl-6,7,8,8a,9,10-hexahydro-10-anthra-cenone (5), besides seven (6-12) known compounds were isolated from the heartwood and sapwood ethanol extracts of Cordia oncocalyx. Moreover, the main isolated compounds were screened using the electrically driven mice vas deferens bioassay, which has a rich pharmacological receptors diversity.

Effects of cardiotonic steroids on isolated perfused kidney and NHE3 activity in renal proximal tubules.

Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of the renal Na/K-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na reabsorption in the proximal tubule, depends on the Na gradient generated by the NKA pump.

Low-level laser therapy (904nm) can increase collagen and reduce oxidative and nitrosative stress in diabetic wounded mouse skin.

Background And Objective: Over the last decade we have seen an increased interest in the use of Low-Level Laser Therapy (LLLT) in diseases that involve increased oxidative stress. It is well established that hyperglycemia in diabetes elicits a rise in reactive oxygen species (ROS) production but the effect of LLLT remains unclear. This study aimed to investigate whether LLLT was able to improve oxidative/nitrosative stress parameters in the wound healing process in diabetic mice.

Uroguanylin modulates (Na++K+)ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways.

Background: The natriuretic effect of uroguanylin (UGN) involves reduction of proximal tubule (PT) sodium reabsorption. However, the target sodium transporters as well as the molecular mechanisms involved in these processes remain poorly understood.

Methods: To address the effects of UGN on PT (Na(+)+K(+))ATPase and the signal transduction pathways involved in this effect, we used LLC-PK1 cells.

Non-nitric oxide based metallovasodilators: synthesis, reactivity and biological studies.

There is an increasing number of compounds developed to target one or more pathways involved in vasodilation. Some studies conducted with azaindole and indazole derivatives showed cardiovascular activity associated with these compounds. Fast and easy structural modification of these organic molecules can be achieved using metal complexes promoting a much larger spatial change than organic strategies, potentially leading to novel drugs.

A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date.