Marco Grasso

Detection of high molecular weight proteins by MALDI imaging mass spectrometry

MALDI imaging mass spectrometry (IMS) is a unique technology to explore the spatial distribution of biomolecules directly on tissues. It allows the in situ investigation of a large number of small proteins and peptides. Detection of high molecular weight proteins through MALDI IMS still represents an important challenge, as it would allow the direct investigation of the distribution of more proteins involved in biological processes, such as cytokines, enzymes, neuropeptide precursors and receptors. In this work we compare the traditional method performed with sinapinic acid with a comparable protocol using ferulic acid as the matrix. Data show a remarkable increase of signal acquisition in the mass range of 20k to 150k Th. Moreover, we report molecular images of biomolecules above 70k Th, demonstrating the possibility of expanding the application of this technology both in clinical investigations and basic science.

Metastatic prostatic adenocarcinoma presenting as a pituitary mass: Shrinkage of the lesion and clinical improvement with medical treatment

Metastatic involvement of the pituitary gland is a very unusual presentation of prostatic cancer. We report a favorable response to medical treatment in such a patient.

Bilateral Varicocele: Impact of Right Spermatic Vein Ligation on Fertility

The most frequent cause of male infertility is left varicocele. The surgical or laparoscopic approach for spermatic vein ligation is considered the best method of treatment. The approach to a clinically significant left varicocele associated with a right varicocele (frequently of a smaller size) is not univocal. We analyzed the seminal responses obtained in 65 patients with bilateral varicocele (grades 2 to 3 on the left side and grade 1 on the right side) assigned randomly to undergo unilateral or bilateral ligation. There were no significant differences between the 2 groups with regard to seminal recovery.

Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa

BackgroundRhoA-Rho kinase complex contributes to keep the cavernosus smooth muscle contracted and its inhibition is considered a potential strategy for the therapy of erectile dysfunction (ED).MethodsWe compared the effects of SAR407899, the Rho-kinase inhibitor Y-27632 and the PDE5 inhibitor sildenafil for their ability to relax corpus cavernosum strips contracted with phenylephrine in healthy and diabetic animals. Strips were obtained from WKY, spontaneous hypertensive (SHR), control CD, and diabetic CD rats, humans, control and diabetic rabbits. Diabetes was induced by streptozotocin or alloxan injection. In vivo penile erection (length) induced by drugs was measured in conscious rabbits.ResultsSAR407899 dose-dependently relaxed the pre-contracted corpora cavernosa in all species, with similar potency and efficacy in healthy vs diabetic rats, WKY vs SHR rats, healthy vs diabetic rabbits (IC50 range from 0.05 to 0.29 μM, Emax range 89 to 97%). In the presence of the NO-synthase (NOS) inhibitor, L-NAME, the SAR407899 response did not decrease in any of the species or experimental conditions. The effect was confirmed in human strips where sildenafil was significantly less potent and effective, with IC50 respectively 0.13 and 0.51 μM; Emax 92 and 43%. Unlike SAR407899, the potency and efficacy of sildenafil and Y27632 were significantly reduced by diabetes and L-NAME. In vivo, SAR407899 dose-dependently induced rabbit penile erection, with greater potency and longer duration of action than sildenafil. Sildenafil, but not SAR407899, was less effective in alloxan-induced diabetes.ConclusionThe induction of penile erection by SAR407899, unlike that by sildenafil, is largely independent of e-NO activity. This suggests its use in erectile dysfunction for diabetic and hypertensive patients where e-NO activity is impaired.

Plasma sex hormone binding globulin in patients with prostatic carcinoma

The concentrations of sex hormone binding globulin (SHBG) were measured in the plasma of 56 men, who were 47 to 85 years of age, by time‐resolved immunofluorometric assay with a monoclonal antibody. Twenty‐five of the men had untreated carcinoma of the prostate and 17 had untreated prostatic hyperplasia. There were 14 healthy control subjects. SHBG levels were significantly higher in patients with prostatic carcinoma (37.6 ± 8.4 nmol/1) than in those with prostatic hyperplasia (24.5 ± 5.2 nmol/1; P < 0.05) or control subjects (14.9 ± 2.8 nmol/1; P < 0.01). It is not known why SHBG levels are higher in patients with carcinoma or hyperplasia of the prostate. The contradictory results obtained in other studies may be due to heterogeneity of the binding globulin causing its values to vary in the different assays used.

Urinary signatures of renal cell carcinoma investigated by peptidomic approaches

Renal Cell Carcinoma (RCC) is typically asymptomatic and surgery usually increases patients lifespan only for early stage tumours. Moreover, solid renal masses cannot be confidently differentiated from RCC. Therefore, markers to distinguish malignant kidney tumours and for their detection are needed. Two different peptide signatures were obtained by a MALDI-TOF profiling approach based on urine pre-purification by C8 magnetic beads. One cluster of 12 signals could differentiate malignant tumours (n = 137) from benign renal masses and controls (n = 153) with sensitivity of 76% and specificity of 87% in the validation set. A second cluster of 12 signals distinguished clear cell RCC (n = 118) from controls (n = 137) with sensitivity and specificity values of 84% and 91%, respectively. Most of the peptide signals used in the two models were observed at higher abundance in patient urines and could be identified as fragments of proteins involved in tumour pathogenesis and progression. Among them: the Meprin 1α with a pro-angiogenic activity, the Probable G-protein coupled receptor 162, belonging to the GPCRs family and known to be associated with several key functions in cancer, the Osteopontin that strongly correlates to tumour stages and invasiveness, the Phosphorylase b kinase regulatory subunit alpha and the SeCreted and TransMembrane protein 1.

Sharing the Emission Budget

Scientific evidence suggests that to have a 75 per cent chance of limiting warming in 2100 to 2°C above the pre-industrial level, the cumulative emissions of CO2 over the period 2010–50 should be capped at 657.1 Gt. The objective of this article is to examine the distribution of such an emission budget by applying different ethical perspectives. In particular, the article first analyses the paths for sharing the emission budget, that is, the major families of distributive patterns that vindicate a number of elementary principles and criteria of distribution. Subsequently, it presents and discusses the shares of the emission budget attributed to states, regions and groupings of states according to the paths investigated and it draws some reflections on the implications of such shares for the ethics of mitigation. Finally, it advances some lessons for international climate policy.

Climate ethics: with a little help from moral cognitive neuroscience

Carbon emissions threaten the stability of climate systems and change climate dynamics in ways that inflict harm on present and future generations. Therefore, the ultimate moral crux of climate change involves harm avoidance and prevention. Moral cognitive neuroscience, and in particular the dual-process theory, indicates that up, close and personal harm triggers deontological moral reasoning, whereas harm originating from impersonal moral violations, like those produced by climate impacts, prompts consequentialist moral reasoning. Accordingly, climate ethics should be based on consequentialist approaches. Moral cognitive neuroscientific research indicates, in fact, that consequentialism is closer to the moral processes and judgements human beings normally use when faced with issues like climate change that involve impersonal notions of harm.

Mediterranean Agriculture Under Climate Change: Adaptive Capacity, Adaptation, and Ethics

In the coming decades, the Mediterranean region is expected to experience various climate impacts with negative consequences on agricultural systems and which will cause uneven reductions in agricultural production. By and large, the impacts of climate change on Mediterranean agriculture will be heavier for southern areas of the region. This unbalanced distribution of negative impacts underscores the significance and role of ethics in such a context of analysis. Consequently, the aim of this article is to justify and develop an ethical approach to agricultural adaptation in the Mediterranean and to derive the consequent implications for adaptation policy in the region. In particular, we define an index of adaptive capacity for the agricultural systems of the Mediterranean region on whose basis it is possible to group its different sub-regions, and we provide an overview of the suitable adaptation actions and policies for the sub-regions identified. We then vindicate and put forward an ethical approach to agricultural adaptation, highlighting the implications for the Mediterranean region and the limitations of such an ethical framework. Finally, we emphasize the broader potential of ethics for agricultural adaptation policy.

Neoadiuvant treatment with intravesical interleukin-2 for recurrent superficial transitional bladder carcinoma Ta-T1/G1-2.

The aim of this study was to evaluate the direct action of IL-2 on recurrent superficial transitional bladder carcinoma and the effect on recurrence rate. 27 patients were submitted to neoadjuvant treatment by intra-vesical instillation of recombinant IL-2 and to transurethral resection. We did not observe any effect on neoplasms but the recurrence rate was less than the expected one. It is possible that treatment of bladder carcinoma with intra-vesical instillation of IL-2 may promote immuno-prophilaxis.