Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome.

CONTEXT: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500-700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity. OBJECTIVE: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF). MAIN OUTCOME MEASURE: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype. RESULTS: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models. CONCLUSION: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels.

Novel triazolium based 11(th) group NHCs: synthesis, characterization and cellular response mechanisms.

The novel NHC ligand precursor 1,4-bis(4-nitrobenzyl)-1H-1,2,4-triazol-4-ium bromide, [HTz((pNO2Bz)2)]Br, has been synthesized and used in the synthesis of the corresponding metal complexes M[Tz((pNO2Bz)2)]Br (M = Cu(I), Ag(I) or Au(I)). These compounds were characterized by several spectroscopic techniques including NMR and mass spectroscopy. The complete series of Au(I), Ag(I) and Cu(I) 1,2,4-triazole based NHC complexes has been synthesized aiming at a SAR study and at identifying the primary cellular targets accounting for their cytotoxic action. The cytotoxic properties of the NHC complexes have been assessed in various human cancer cell lines, including cisplatin sensitive and resistant cells, the most efficacious antiproliferative compound being Cu(I)-NHC, which was able to promote a growth inhibitory effect up to ten times higher than that promoted by cisplatin. A detailed analysis of molecular and cellular pharmacology allowed us to elucidate the role of the metallic core in determining the biological properties. In particular, gold(I) and silver(I) NHC complexes were found to be able to hamper mammalian thioredoxin reductase (TrxR) activity in human A431 cervical cancer cells, ultimately leading to a dramatic alteration of the cellular redox state and to the induction of cell death via apoptosis. Conversely, the copper NHC complex was found to be capable of inhibiting proteasome functionality thus determining the induction of a non-apoptotic cell death pathway.

Homoleptic phosphino copper(I) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity.

Homoleptic, tetrahedral Cu(i) complexes of the type [Cu(P)4]BF4 (1-3), where P are the phosphine ligands, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) and 2-thia-1,3,5-triaza-phosphoaadamantane-2,2-dioxide (PTA-SO2), have been prepared. Novel complexes [Cu(DAPTA)4]BF42 and [Cu(PTA-SO2)4]BF43 have been fully characterized by means of spectroscopic methods, corroborated by XAS-EXAFS analysis of 2. In vitro cell culture experiments revealed a significant antiproliferative activity for Cu(i) compounds against several human cancer cell lines derived from solid tumors with preferential cell growth inhibition towards tumour compared to non-malignant cells. In vitro monitoring of migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) showed an anti-angiogenic effect of copper(i) complexes at sub-cytotoxic concentrations. In vivo studies on the antitumor efficacy and ability to inhibit angiogenesis confirmed the dual cytotoxic and anti-angiogenic properties of Cu(i) derivatives.

Efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) performed in patients with Periampullary duodenal diverticula (PAD).

BACKGROUND AND AIM: Periampullary diverticula (PAD) are found in 9-32% of patients who undergo endoscopic retrograde cholangiopancreatography (ERCP). PAD are acquired lesions which are rare in patients <40 years, but increasing with age. Several endoscopic studies have revealed an association between PAD and common bile duct (CBD) stones. The presence of a papilla located in the diverticula is also frequent (6.8-54.9%) and represents a restrictive factor for successful cannulation. MATERIALS AND METHODS: A retrospective analysis has been made of data related to the patients with PAD treated at our GI Unit (small center with low case volume), who underwent ERCP in the period 1st January 2010 to 31st March 2014. For each patient were analyzed data regarding sex, age at diagnosis, indication to ERCP, cannulation rate, endoscopic treatment and complications. PAD were classified in 3 different types according to the position of the major papilla. RESULTS: A total of 647 ERCPs have been performed of which 77 (16.5%) in pts with PAD (48 F, 29 M, mean age: 78.3 years; range: 48-95). PAD type I (inside the diverticulum) were found in 22 pts (28.6 %), Type II (in the margin of the diverticulum or between two PADs) in 36 pts (46.7 %) of which 12 cases between two PADs, type III (near the diverticulm) in 19 pts (24.7 %). The indication for ERCP were: 72 CBD stones (93.5%), 3 cholangiocarcinoma (3.9%) and 2 pancreatic head cancer (2.6%). In cases of difficult cannulation, precut was performed in 12 pts (15.6%). Deep CBD cannulation and endoscopic sphincterotomy (ES) was achieved in 70 cases (90.9%). The other 7 case of failure were all in patients with CBD stones. Complete clearance of CBD stones was achieved in 57 patients (87.7%) (57/65 ERCP/ES). Stent placement was necessary in 8 cases (12.3%) (8/65 ERCP/ES), due to multiple large stones. The adverse events related to ERCP/ES included 4 intraprocedural bleeding (5.7%) (4/70 ERCP/ES) and 1 mild pancreatitis (1.4%) (1/70 ERCP/ES), all managed conservatively. CONCLUSIONS: Our data show that ERCP is a safe procedure also in patients with PAD, with a good success rate and low complications.

Large symptomatic simple hepatic cyst with gastric compression treated with percutaneous drainage.

Nonparasitic hepatic cysts consist of a heterogeneous group of disorders, which differ in etiology, prevalence, and manifestations. Simple hepatic cysts are considered nonparasitic ones. These are a result of congenital anomalies of the biliary system, and these may be single or multiple. Generally, hepatic cysts are incidentally found during occasional laparotomy or laparoscopy, necropsy, and even during routine ultrasound or computerized tomography (CT) scan. Nowadays, with improving diagnostic techniques, hepatic cysts are becoming more common. Generally these lesions are asymptomatic. However, if they grow, they may become symptomatic. Symptoms depend on the size and location. When symptoms developed, these must be treated. Compressive complications due to local "liver mass" effect include: portal hypertension, edema due to caval compression, jaundice and arrhythmia and duodenal obstruction. Gastric extrinsic compression by liver cysts has been poorly described. Herein, we present a case of a female in whom percutaneous drainage of a large simple hepatic cysts not complicated was performed in order to reduce signs of gastric compression.

Benign pneumoperitoneum after percutaneous endoscopic gastrostomy (PEG) feeding tube placement: do not be afraid!

In order to ensure enteral feeding, placement of a percutaneous endoscopic gastrostomy (PEG) is considered a standard care for patients with oropharyngeal malignancies. Benign pneumoperitoneum is a complication of PEG feeding tube placement and it is usually an incidental finding that arises, generally, immediately following the procedure. We report a case of a benign pneumoperitoneum, developed 48 hours after the procedure, which was treated conservatively.

Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader-Willi syndrome.

BACKGROUND: Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear. OBJECTIVES: To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males. METHODS: Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years. RESULTS: Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH. CONCLUSION: PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis).

The impact of one night of sleep deprivation on moral judgments.

Recent studies have shown the existence of a relationship between sleep and moral judgment. In this study, we investigated whether one night of sleep deprivation affects the ability to judge the appropriateness of moral dilemmas. Forty-eight students had to judge 30 moral dilemmas at test, after a night of home sleep, and another 30 dilemmas at retest, following one night of continuous wakefulness. The 60 dilemmas (20 moral impersonal, 20 moral personal, and 20 non-moral) were selected from Greene's dilemmas. Both groups judged the appropriateness of personal and impersonal dilemmas in the same way. A close to significant effect of sleep deprivation was observed on the reaction times for impersonal moral dilemmas, to which the deprived subjects responded faster (p = .05) than the control subjects. However, this was not the case for personal ones, for which no difference was significant. This result shows a greater ease/speed in responding to the (impersonal) dilemmas, which induce low emotional engagement after sleep deprivation, although the willingness to accept moral violations is not affected. This suggests that one night of sleep loss selectively influences the response speed only for moral impersonal dilemmas, probably due to disinhibition processes. The quality of moral judgment dilemmas does not seem to be easily influenced by a single night of sleep deprivation, but only by a longer lack of sleep.

Electroencephalographic sleep inertia of the awakening brain.

Sleep inertia (SI) denotes a period of hypovigilance, confusion and impaired cognitive and behavioral performance that immediately follows awakening. Based on the observation that the reactivation of some cortical areas is faster than other upon awakening, here we examined regional differences between presleep and postsleep waking period. Moreover, we also compared rapid eye movements (REM) and stage 2 non-rapid eye movements (NREM) awakenings in a within-subject design. Presleep and postsleep waking electroencephalogram (EEG; 5 min with eyes-closed and 5 min with eyes-open) of 18 healthy subjects (12 males, mean age=23.8±2.3 years) were recorded from 19 derivations. Participants slept for two consecutive nights in the laboratory. In one night they were awakened from stage 2 NREM, while in the other from REM sleep. EEG power spectra were calculated across the following bands: delta (1-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta-1 (13-16 Hz) and beta-2 (17-24 Hz). Moreover, a detailed hertz-by-hertz analysis has been repeated in the 2-4 Hz frequency range. Postsleep wakefulness, compared to presleep, is characterized by a generalized decrease of higher beta-1 and beta-2 EEG power over almost all scalp locations. A detailed analysis of topographical modifications in the low-frequency range showed that postsleep wakefulness is characterized by an increased delta activity in the posterior scalp locations, and by a concomitant frontal decrease compared to presleep. Moreover, it was found a prevalence of EEG power in the high frequency ranges (beta-1 and beta-2) upon awakening from stage 2 compared to REM awakenings over the left anterior derivations. Altogether these findings support the hypothesis that a generalized reduction in beta activity and increased delta activity in more posterior areas upon awakening may represent the EEG substratum of the sleep inertia phenomenon.

[Budd-Chiari syndrome and splanchnic vein thrombosis: masked myeloproliferative neoplasms and JAK2V617F]. / Sindrome di Budd-Chiari e trombosi delle vene splancniche: neoplasie mieloproliferative mascherate e mutazione di JAK2V617F.

The Budd-Chiari Syndrome (BCS) and the splanchnic vein thrombosis are characterized by hepatic venous outflow obstruction, generally due to venous thrombosis. These rare diseases are usually caused by multiple concurrent factors, including acquired and inherited thrombophilias. Since the diagnosis of myeloproliferative neoplasms (MPNs) is often difficult in patients with BCS and splanchnic vein thrombosis because of spleen enlargement, secondary pancytopenia and bleeding disorders, recent observations have included in the diagnostic work-up the analysis of the JAK2 mutation. The revision of several recent reports clarify the importance of the JAK2V617F detection in the diagnostic work-up of the BCS and splanchnic vein thrombosis, allowing the demonstration of masked MPNs among these cases that may benefit, in the near future, of target molecular therapies directed toward the JAK2 mutation.

Solution behaviour and biological activity of bisamidine complexes of platinum(II).

A series of platinum(II) amidine complexes were previously prepared with the aim of obtaining a new class of platinum-based antitumour drugs. This series includes compounds of the type cis--[PtCl2{Z-HN=C(NHMe)Me}2] and trans-[PtCl2{Z-HN=C(NHMe)Me}2] (1, 2), cis-[PtCl2{E-HN=C(NMe2)Me}2] and trans-[PtCl2{E-HN=C(NMe2)Me}2] (3, 4), cis-[PtCl2{Z-HN=C(NHMe)Ph}2] and trans-[PtCl2{Z-HN=C(NHMe)Ph}2] (5, 6), and cis-[PtCl2{HN=C(NMe2)Ph}2] and trans-[PtCl2{HN=C(NMe2)Ph}2] (7, 8). The reactions with dimethyl sulfoxide were studied for complexes 5-8; the formation of cationic species containing coordinated dimethyl sulfoxide was demonstrated by NMR experiments and electrospray ionization mass spectrometry. In this work, the amidine platinum(II) complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicate that the benzamidine complex 8 was the most effective derivative also circumventing acquired cisplatin resistance as demonstrated by chemosensitivity tests performed on cisplatin-sensitive and cisplatin-resistant cell lines. The studies concerning the cellular DNA damage on both parental chemosensitive and resistant sublines suggest for the new trans-amidine complex a different mechanism of action compared with that exhibited by cisplatin.

Synthesis and biological in vitro evaluation of novel PEG-psoralen conjugates.

Psoralens are well-known photosensitizers, and 8-methoxypsoralen and 4,5',8-trimethylpsoralen are widely used in photomedicine as "psoralens plus UVA therapy" (PUVA), in photopheresis, and in sterilization of blood preparations. In an attempt to improve the therapeutic efficiency of PUVA therapy and photopheresis, four poly(ethylene glycol) (PEG)-psoralen conjugates were synthesized to promote tumor targeting by the enhanced permeability and retention (EPR) effect. Peptide linkers were used to exploit specific enzymatic cleavage by lysosomal proteases. A new psoralen, 4-hydroxymethyl-4',8-dimethylpsoralen (6), suitable for polymer conjugation was synthesized. The hydroxy group allowed exploring different strategies for PEG conjugation, and linkages with different stability such ester or urethanes were obtained. PEG (5 kDa) was covalently conjugated to the new psoralen derivative using four different linkages, namely, (i) direct ester bond (7), (ii) ester linkage with a peptide spacer (8), (iii) a carbamic linker (9), and (iv) a carbamic linker with a peptide spacer (12). The stability of these new conjugates was assessed at different pHs, in plasma and following incubation with cathepsin B. Conjugates 7 and 8 were rapidly hydrolyzed in plasma, while 9 was stable in buffer and in the presence of cathepsin B. As expected, only the conjugates containing the peptide linker released the drug in presence of cathepsin B. In vitro evaluation of the cytotoxic activity in the presence and absence of light was carried out in two cell lines (MCF-7 and A375 cells). Conjugates 7 and 8 displayed a similar activity to the free drug (probably due to the low stability of the ester linkage). Interestingly, the conjugates containing the carbamate linkage (9 and 12) were completely inactive in the dark (IC50 > 100 microM in both cell lines). However, antiproliferative activity become apparent after UV irradiation. Conjugate 12 appears to be the most promising for future in vivo evaluation, since it was relatively stable in plasma, which should allow tumor targeting and drug release to occur by cathepsin B-mediated hydrolysis.

Mixed complexes of Pt(II) and Pd(II) with ethylsarcosinedithiocarbamate and 2-/3-picoline as antitumor agents.

The [M(ESDT)Cl](n) (M=Pt(II), Pd(II); ESDT=EtO(O)CCH(2)N(CH(3))CS(2)(-), ethylsarcosinedithiocarbamate ion) species have been reacted with 2- or 3-picoline in dichloromethane in order to obtain mixed ligand complexes of the type [M(ESDT)(L)Cl] (L=2-picoline, 3-picoline). The synthesized compounds have been isolated, purified and characterized by means of elemental analyses, (1)H-/(13)C-/(1)H(13)C-HMBC (heteronuclear multiple bonding coherence) NMR and FT-IR spectroscopy. The biological activity of the compounds reported here has been then determined in terms of cell growth inhibition, DNA synthesis inhibition, detection of interstrand cross-links and DNA-protein cross-links, and micronuclei (MN) detection on a panel of tumor cell lines both sensitive and resistant to cisplatin. On the basis of the experimental results, coordination in the above mentioned complexes takes place in a near square-planar geometry, the dithiocarbamate moiety acting as a chelating agent, whereas the two remaining coordination sites are occupied by a chlorine atom and an amino ligand. Above all, [Pt(ESDT)(2-picoline)Cl] complex has shown very encouraging cytotoxicity levels higher or, at least, comparable to those exerted by cisplatin in the same experimental conditions.

Characterization studies and cytotoxicity assays of Pt(II) and Pd(II) dithiocarbamate complexes by means of FT-IR, NMR spectroscopy and mass spectrometry.

The precursors [M(ESDTM)Cl(2)] (M=Pt(II), Pd(II); ESDTM=EtO(2)CCH(2)(CH(3))NCS(2)Me, S-methyl(ethylsarcosinedithiocarbamate)) were synthesized as previously reported [J. Inorg. Biochem. 83 (2001) 31] and used to obtain [M(ESDT)Cl](n) (ESDT=ethylsarcosinedithiocarbamate anion) species. The complexes formed through reaction between [M(ESDT)Cl](n) and the two chiral amino-alcohols synephryne (Syn) and norphenylephrine (Nor) have been synthesized, with the ultimate goal of preparing mixed dithiocarbamate/amino metal complexes of the type [M(ESDT)(Am)Cl] (Am=Syn, Nor). These compounds have been isolated, purified and characterized by means of FT-IR, mono- and bidimensional NMR spectroscopy and mass spectrometry ESI/MS (electronspray mass spectra). The experimental data suggest that in all cases coordination of the dithiocarbamate ligand (ESDT) takes a place through the two sulfur atoms, the -NCSS moiety acting as a symmetrical bidentate chelating group, in a square-planar geometry around the M(II) ion, while the other two coordination positions are occupied by the chlorine atom and the amino-alcohol ligand, respectively. In particular, synephrine and norphenylephrine appear to be bound to the metal atom through the amino nitrogen atom by means of a dative bond. Finally, the biological activity of the new complexes has been studied by MTT (tetrazolio salt reduction) test and by detecting the inhibition of DNA synthesis and of clonal growth in various cancer cell lines. All Pd(II) derivatives showed a noticeable activity very close to that of cisplatin, used as reference drug. Moreover, they showed significantly reduced cross-resistance to cisplatin in a pair of cell lines (2008/C13*) with known acquired cisplatin resistance mechanisms.

Pt(II) and Pd(II) derivatives of ter-butylsarcosinedithiocarbamate. Synthesis, chemical and biological characterization and in vitro nephrotoxicity.

This work reports on the synthesis, characterization and biological activity of new coordination compounds of the type [M(TSDTM)X(2)] (M=Pt(II), Pd(II); X=Cl, Br; TSDTM=ter-butylsarcosine(S-methyl)dithiocarbamate) and [Pd(TSDT)X](n) (TSDT=ter-butylsarcosinedithiocarbamate) in order to study their behavior as potential antitumor agents. All the synthesized compounds were characterized by means of elemental analysis, FT-IR, (1)H and (13)C-NMR spectroscopy and thermogravimetric analysis, suggesting a chelate S,S' structure of the TSDTM/TSDT ligand in a square-planar geometry. Finally, the synthesized complexes have been tested for in vitro cytotoxic activity against human leukemic HL60 and adenocarcinoma HeLa cells; the most active compound [Pt(TSDTM)Br(2)], characterized by IC(50) values very similar to those of the reference compound (cisplatin), was also tested for in vitro nephrotoxicity showing a very low renal cytotoxicity as compared to cisplatin itself.

Synthesis, characterization and in vitro cytotoxicity of new organotin(IV) derivatives of N-methylglycine.

The synthesis and characterization of new coordination compounds of some diorganotins(IV) with N-methylglycine (sarcosine) are reported; all these derivatives mainly tend to assume a chelate structure. As single crystals were not obtained, a large number of experimental techniques were used to accomplish a definitive characterization and determination of their structure. Results obtained by (1)H/(119)Sn NMR, FT-IR and (119)mSn-Mössbauer spectroscopy and thermogravimetric analysis allow us to deduce the pentacoordination for 1:1 (Sn/sarcosine) derivatives [R(2)SnCl(2)(Sar)](+)Cl(-) (R=Me, n-Bu) in a trigonal-bipyramidal structure, and the hexacoordination for 1:2 complexes [R'(2)Sn(Sar)(2)](2+)2Cl(-) (R'=Me, n-Bu, Ph) in an octahedral structure; however, the probability of partially or totally non-chelate structures for some adducts increases with the steric hindrance of the R/R' groups and the number of the sarcosine molecules bound to the tin atom, so that they give rise to fluxional equilibria in solution. Finally, the synthesized compounds have been tested for in vitro cytotoxic activity against human adenocarcinoma HeLa cells showing, in some cases, strong activity even at low concentration.

Synthesis of a new platinum(II) complex: anticancer activity and nephrotoxicity in vitro.

New mixed dithiocarbamate-amino Pt(II) complex ([Pt(ESDT)(Py)Cl]) has been recently synthesised with the aim to produce potential anticancer drug able to conjugate cytostatic activity with lack of nephrotoxicity. This complex contains: (1) an amino ligand; (2) a good leaving group (halide); and (3) an S-containing chelating agent potentially able to protect the metal centre from its interaction with S-containing protein-legating sites that are believed to be at the basis of the nephrotoxicity of Pt(II)-based drugs. This complex has been found to be effective as an antiproliferative agent (more active than cis-platin) towards a normal human adenocarcinoma cell line and the corresponding cis-platin-resistant C13 strain. Toxicity tests on the kidney were performed by means of a renal cortical slice model. The slices, prepared with a Brendel-Vitron slicer, were incubated with different doses (0.125-5.0 x 10(-4) M, final concentration) of [Pt(ESDT)(Py)Cl] or cis-platin dissolved in methyl sulphoxide. The platinum(II) complex showed very low renal cytotoxicity as compared with cis-platin; in particular, lipid peroxidation induced by cis-platin appeared about five-fold higher than that induced by [Pt(ESDT)(Py)Cl]. In conclusion, besides being less toxic for the kidney, the results showed that the new synthesised platinum(II) complex appeared in vitro more effective than cis-platin when tested on sensitive and resistant cis-platin tumour cell lines.