A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies.

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential 'Metal-Protein Attenuating Compound' for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200mgkg-1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24h after intraperitoneal administration. After 48h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well.

Glomerular filtration rate measured by (51)Cr-EDTA clearance: Evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis.

INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ((51)Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using (51)Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ((51)Cr-EDTA) and (99m)Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6+/-21.8 ml/kg/1.73 m(2) in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1+/-28.7 ml/kg/1.73m(2) in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+/-14.8 ml/ kg/1.73m(2), p=0.001) and an insignificant change in the group without RAS (to 62.2+/-23.6 ml/kg/1.73m(2), p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant differences in differential renal function from baseline to post-captopril images in either group. CONCLUSIONS: Captopril induced a decrease in the GFR that could be quantitatively measured with (51)Cr-EDTA. The reduction is more pronounced in hypertensive patients with RAS.

Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m² in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m² in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m², p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m², p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did...

Optimization of antibody labeling with rhenium-188 using a prelabeled MAG3 chelate.

We report the optimization of polyclonal IgG labeling by 188Re using S-benzoyl-MAG(3) as a model for labeling monoclonal antibodies (MoAb). We examined the in vitro stability of the labeled protein and its localization and excretion in mice with induced focal inflammation. Stability in serum was greater than 85.5% after 24 h. Biodistribution and imaging studies following administration to mice showed mainly renal and hepatic excretion and high IT/NT ratios (4.5 and 4.6) at 24 and 48 h, respectively. This indirect method of labeling antibodies using a 188Re-labeled active ester of MAG(3) produced 188Re-MAG(3)-IgG of high in vitro stability and favorable uptake at sites of focal inflammation.

Consideracoes sobre a biodisponibilidade do ferro dos alimentos / Considerations regarding eron biovailability

Neste artigo se apresenta uma revisao documentada com mais de 60 referencias sobre o tema da disponibilidade do ferro. O trabalho oferece uma secao dedicada a terminologia empregada, enfatizando a conveniencia do termo "biodisponibilidade ou disponibilidade biológica de nutrientes" que tem certa discrepancia. Depois estuda os factores extrínsecos ou fisiológicos e os fatores intrínsecos ou dietéticos que afectan a disponibilidade do ferro. A continuacao se apresenta uma discussao sobre a biodisponibilidade do ferro dos alimentos de origem animal e vegetal, dos alimentos fortificados com sais de ferro e dos alimentos com ferro provenientes de contaminacao. O artigo refere como pesquisadores compararam métodos "in vitro" e "in vivo" para determinar a biodisponibilidade do ferro, concluindo que ambos os métodos devem ser associados. Para finalizar explica que apesar das mudancas ocurridas em diversos ambitos, novas questoes surgen sobre a importancia do ferro dos alimentos na solucao do problema da deficiencia desde mineral