RESUMO
In recent years, bisphosphonate chemistry has undergone an exponential growth due to the potential applications of these compounds in medicine and nanobiomaterial research. In this paper we describe the synthesis methods of different families of methacrylic monomers bearing a bisphosphonate with varying lengths of the chain, PEG linkers and more or less hydrolysable functions such as ester, carbamate or amide.
RESUMO
A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2(∗) contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that γFe(2)O(3)@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.
RESUMO
AIM OF THE STUDY: Renal protection and antiurolithiasic effects of two extracts of Paronychia argentea (PA), a traditional Algerian plant commonly known as Algerian tea, were evaluated. This study was carried out to determine whether the aqueous extract (APA) or the butanolic extract (BPA) of aerial parts could prevent or reduce calculi aggregation in experimental calcium oxalate (Ox) nephrolithiasis in Wistar rats. MATERIALS AND METHODS: The two extracts (APA and BPA) were administrated orally and daily, during 28 days to nephrolithiasic treated rats at the dose of 250, 500 mg/kg b.w. and 10, 20mg/kg b.w. respectively. Body weight, renal index, liver index, serum level of creatinine, uric acid, urea, K(+), Ca(2+), Mg(2+), Na(+) and transaminase (alanine aminotransferase, ALT; aspartate aminotransferase, AST), phosphatase alkaline activity (PAL) were evaluated following the 28 days treatment in rats. In addition histopathological changes in kidney and liver were stained in hematoxylin eosin (HE). RESULTS: The effect of the extracts could be advantageous in preventing urinary stone retention by reducing renal necrosis and thus inhibit crystal retention. In contradiction with APA, the two doses of BPA attenuated elevation in the serum creatinine (p<0.01) and blood urea levels (p<0.01) (nephroprotective effect). However, the increase in ALT (27%) and PAL (31-51%) serum levels and in the relative liver weights (p<0.01) in the groups treated with doses of APA may indicate that this extract has not a hepatoprotective effect against oxalate toxicity. CONCLUSIONS: The presented data indicate that administration of the butanolic extract of aerial parts to rats with NaOx induced lithiasis, and reduced and prevented the growth of urinary stones in experimental calcium oxalate nephrolithiasis in Wistar rats.
Assuntos
Oxalato de Cálcio/metabolismo , Caryophyllaceae , Rim/patologia , Nefrolitíase/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Creatinina/sangue , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/metabolismo , Cálculos Renais/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Necrose/prevenção & controle , Nefrolitíase/induzido quimicamente , Nefrolitíase/patologia , Tamanho do Órgão/efeitos dos fármacos , Oxalatos , Componentes Aéreos da Planta , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Ureia/sangueRESUMO
The conformation of the benzodiazepine-like decapeptide, YLGYLEQLLR, corresponding to residues 91-100 of bovine alphaS1-casein, has been examined in SDS micelles using CD, two-dimensional 1H-NMR and restrained molecular-dynamics simulation. Evidence is presented that the decapeptide adopts a rigid structure in water/SDS micellar medium, but not in water or dimethylsulfoxide. The three-dimensional structure, consistent with the proton-proton distances obtained from the quantitative analysis of the two-dimensional NOEs, was generated by restrained energy minimization and molecular-dynamics simulation. In water/SDS micellar medium, YLGYLEQLLR adopts an amphipathic helicoid structure with distinct hydrophobic and hydrophilic faces. The relative disposition of the tyrosine aromatic rings was compared with that of the aromatic rings in the benzodiazepines.