Valerio Podio

In Vitro and In Vivo Study of Solid Lipid Nanoparticles Loaded with Superparamagnetic Iron Oxide

Solid Lipid Nanoparticles (SLN) are already under investigation as a pharmaceutical tool able to change the pharmacokinetic and biodistribution of carried molecules. SLN are able to target drugs to lymph after duodenal administration and to overcome the Blood Brain Barrier (BBB). In this study, superparamagnetic SLN have been prepared, have colloidal size, in vitro analysis showed relaxometric properties similar to Endorem®. In vivo Magnetic Resonance Imaging (MRI) of the central nervous system (CNS) with both SLN and Endorem® showed that superparamagnetic SLN have slower blood clearance than Endorem®. MRI data are consistent with CNS uptake of SLN lasting up to the end of the experiment (135 min). These findings confirm the ability of SLN to overcome the BBB; SLN might be used as a CNS MRI contrast agent.

Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans

Reduced cardiac mass and performances are present in GH deficiency and are coun-teracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocar-dial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexare-lin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6±88.1 vs 1739.3±262.2 μg/l/min for 90 min) while aldosterone and cate-cholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4±2.1 vs 62.1±2.3%, 90.6±3.4 vs 92.0±2.5 mm Hg, 62.3±1.8 vs 66.7±2.7 bpm). HEX increased LVEF (70.7±3.0 vs 64.0±1.5%, p<0.03) without significant changes in MBP and HR (92.8±4.7 vs 92.4±3.2 mmHg, 63.1±2.1 vs 67.0±2.9 bpm). LVEF significantly raised at 15 min, peaked at 30 min and lasted up to 60 min after HEX. These findings suggest that in man, the acute administration of Hexarelin exerts a short-lasting, positive inotropic effect. This effect seems GH-in-dependent and might be mediated by specific GHS myocardial receptors.

Long-Term Functional Evaluation of the Treated Kidney in a Prospective Series of Patients Who Underwent Laparoscopic Partial Nephrectomy for Small Renal Tumors

BACKGROUND Renal scintigraphy may allow long-term monitoring of ischemic damage after partial nephrectomy (PN). OBJECTIVE Evaluate use of renal scintigraphy for evaluating long-term effects of warm ischemia on renal function in patients with a normal contralateral kidney. DESIGN, SETTING, AND PARTICIPANTS We prospectively examined kidney function of 54 patients who underwent laparoscopic PN (LPN). Minimum follow-up time was 4 yr. INTERVENTION LPN was performed with warm ischemia by transperitoneal or retroperitoneal approach. MEASUREMENTS Demographic, perioperative, and pathologic data and postoperative complications were registered. Split renal function (SRF) and effective renal plasma flow (ERPF) were evaluated by renal scintigraphy preoperatively, at 3 and 12 mo postoperatively, then yearly. Baseline weighted differentials (b-WDs) of both SRF and ERPF in the affected kidney were calculated between baseline condition and every time point. Multivariate linear regression was used to find independent variables for increased b-WDs at 3 and 48 mo. P values<0.05 were considered significant. RESULTS AND LIMITATIONS The SRF and ERPF of kidneys treated by LPN decreased significantly at month 3 and subsequently remained stable through the duration of follow-up. Conversely, neither serum creatinine nor estimated glomerular filtration rate changed significantly during follow-up. The regression model showed statistical significance at month 3 for warm ischemia time (WIT) and age, whereas at 48 mo, statistical significance was reached by WIT alone. No new onset of cardiovascular disease was registered. No evidence of local recurrence was recorded with computed tomography scan. Our study may be underpowered due to small sample size; however, this is one of the largest long-term prospective series using renal scintigraphy to evaluate the renal function after LPN. CONCLUSIONS WIT contributes to irreversible kidney damage observed at month 3 that does not appear to worsen.

Cardiac effects of hexarelin in hypopituitary adults.

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean+/-S.E.M.: 42.0+/-4.0 year) were studied by equilibrium radionuclide angiocardiography after i.v. administration of hexarelin, a peptide GH secretagogue. Data for these patients were compared with those for nine adult male controls (37.0+/-2.7 year). The GH response to hexarelin was negligible in patients with GHD compared to control subjects (CS) (peak: 1.9+/-0.9 vs. 45.7+/-3.6 microg/l, P<0.001). Basal left ventricular ejection fraction (LVEF) in patients with GHD was lower than that in CS (50+/-1% vs. 63+/-2%, P<0.001). Hexarelin administration increased LVEF both in patients with GHD and in CS (peak: 57+/-2 vs. 70+/-2, respectively, P<0.05 vs. baseline) without changing catecholamine levels, mean blood pressure (MBP), or cardiac output in either group. In conclusion, the acute administration of hexarelin exerts a short-lasting positive inotropic effect in humans, probably GH-independent and mediated by specific myocardial receptors for GH secretagogues.

Biodistribution of stealth and non-stealth solid lipid nanospheres after intravenous administration to rats

Drug‐free stealth and non‐stealth solid lipid nanospheres (SLNs) were administered intravenously to rats to evaluate their tissue distribution and their transport across the blood‐brain barrier.

Evaluation of functional outcomes after laparoscopic partial nephrectomy using renal scintigraphy: clamped vs clampless technique.

To examine differences in postoperative renal functional outcomes when comparing clampless with conventional laparoscopic partial nephrectomy (LPN) by using renal scintigraphy, and to identify the predictors of poorer postoperative renal functional outcomes after clampless LPN.

The Role of Cortex in Central Pain Syndromes

The role of the somatosensory cortex in central pain syndromes is widely questioned. Two recent position emission tomography studies detected a strong activation of the parietal and cingular cortices after brief nociceptive stimuli. On the other hand, a recent single photon emission computed tomography study found no cortical activation in five patients affected by central poststroke pain and algodystrophia. In this study, we present the single photon emission computed tomography findings in five patients suffering from central pain syndromes. Two of these, one with facial postrhizotomy anesthesia dolorosa and the other with central poststroke pain, showed a decrease of blood flow in the parietal lobe, further decreasing after stimulation by nonpainful maneuvers. Our results suggest that somatosensory cortical areas might be involved in the generation of anomalous pain states in some cases of central pain syndromes.

99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression

Recently, thyroid 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of 99mTc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between 99mTc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. Methods: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative 99mTc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. Results: Visual and semiquantitative 99mTc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative 99mTc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative 99mTc-MIBI RI in those cases with strong MRP1 apical expression. Conclusion: Semiquantitative 99mTc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the 99mTc-MIBI results and provides tissue information on the molecular mechanisms responsible for 99mTc-MIBI images in thyroid lesions.

Growth hormone-independent cardiotropic activities of growth hormone-releasing peptides in normal subjects, in patients with growth hormone deficiency, and in patients with idiopathic or ischemic dilated cardiomyopathy

Growth hormone releasing peptides (GHRPs) are synthetic molecules endowed with potent neuroendocrine activities mediated by specific receptors in the pituitary and in the central nervous system. GHRPs receptors have been reported even in perpheral tissues, particularly in the myocardium, where they probably mediate growth hormone (GH)-independent activities. We studied in humans the cardiac effects of hexarelin administration in 7 normal adults, in 7 severe GH-deficient patients, and in 12 patients with severe dilated cardiomyopathy. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP), heart rate (HR), and GH levels were evaluated at baseline and every 15 min up to 60 min after acute 2.0 μg/kg iv hexarelin administration. Basal LVEF in dilated cardiomyopathy was impaired and lower (p<0.001) than in GH deficiency, in turn lower (p<0.001) than in normal subjects. Hexarelin significantly (p<0.05) increased LVEF in normal and in GH-deficient subjects, but not in dilated cardiomyopathy, without significant variations in MBP and HR. Hexeralin significantly (p<0.05) increased GH levels in normal subjects and in dilated cardiomyopathy but not in GH deficiency. These findings suggest that, in humans, the acute administration of hexarelin exerts a GH-independent positive inotropic effect likely mediated by specific GHRPs myocardial receptors.

Assessing the Accuracy and Reproducibility of Computer-Assisted Analysis of 123I-FP-CIT SPECT Using BasGan (V2)

Over the last two decades 123I‐FP‐CIT‐SPECT, has been used to discriminate neurodegenerative Parkinsonian syndrome from other diseases. BasGan is a freely available software that assists 123I‐FP‐CIT‐SPECT evaluation by estimating semiquantitative values for each basal nucleus and compares the results to a database of healthy subjects. The aims of this study were: (1) to assess the accuracy of qualitative analysis and of semiquantitative, BasGan‐assisted evaluations of 123I‐FP‐CIT‐SPECT; (2) to compare the accuracy of both methods when applied to “doubtful” cases; (3) to appreciate the reproducibility of the BasGan‐assisted evaluations.