Bone tumor-targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells.

Platinum-based drugs such as cisplatin are very potent chemotherapeutics, whereas radioactive platinum (195mPt) is a rich source of low-energy Auger electrons, which kills tumor cells by damaging DNA. Auger electrons damage cells over a very short range. Consequently, 195mPt-based radiopharmaceuticals should be targeted toward â€‹tumors to maximize radiotherapeutic efficacy and minimize Pt-based systemic toxicity. Herein, we show that systemically administered radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes specifically accumulate in intratibial bone metastatic lesions in mice. The 195mPt-BP complexes accumulate 7.3-fold more effectively in bone 7 days after systemic delivery compared to 195mPt-cisplatin lacking bone-targeting bisphosphonate ligands. Therapeutically, 195mPt-BP treatment causes 4.5-fold more γ-H2AX formation, a biomarker for DNA damage in metastatic tumor cells compared to 195mPt-cisplatin. We show that systemically administered 195mPt-BP is radiotherapeutically active, as evidenced by an 11-fold increased DNA damage in metastatic tumor cells compared to non-radioactive Pt-BP controls. Moreover, apoptosis in metastatic tumor cells is enhanced more than 3.4-fold upon systemic administration of 195mPt-BP vs. radioactive 195mPt-cisplatin or non-radioactive Pt-BP controls. These results provide the first preclinical evidence for specific accumulation and strong radiotherapeutic activity of 195mPt-BP in bone metastatic lesions, which offers new avenues of research on radiotherapeutic killing of tumor cells in bone metastases by Auger electrons.

Body composition, eating behavior, food-body concerns and eating disorders in adolescent girls.

AIMS: Dieting is a behavioral phenomenon which is becoming more frequent among adolescents and the search for weight loss, through dieting, may result in an unbalanced nutrition both quantitatively and qualitatively. Our study intended to look at the eating habits and behavior on a cohort of adolescent girls to verify the presence of unbalanced diets and the prevalence of eating disorders with particular attention to the partial syndromes (EDNOS). METHODS: A cross-sectional double-stage study was carried out on a group of schoolgirls in the suburbs of Naples. We assessed anthropometrical measures, body composition (skinfolds and bioimpedance analysis), dietary intake by means of 3-day food records and we administered the Eating Disorder Inventory 2 and Psychosocial Factor Risk Questionnaire. A multidisciplinary and double-stage approach had been used to get a better diagnosis of eating disorders in our sample. RESULTS: 156 adolescent girls, 14-18 years old, took part in our study. Height, weight, and BMI were 160.38 cm, 58 kg and 22.6, respectively. Analysis of food intake showed that all the values reported, with the exception of lipids and sodium, were below the recommendations by LARN. We observed a prevalence of 1.28% of bulimia nervosa, 1.28% of binge eating, and 10.25% of eating disorders not otherwise specified. EDI 2 and PRFQ confirmed how important drive for thinness and body dissatisfaction dimensions are when we deal with adolescent girls and with the phenomenon of dieting. The study confirmed the validity of the PRFQ questionnaire to evaluate mass media influence on body perception and eating behavior of adolescents. CONCLUSION: Multidisciplinary and well-designed studies are needed to systematically and accurately study eating habits and behavior of adolescents to tackle more efficiently the increasing spread of eating disorders and obesity.

Interdisciplinary treatment of a female outpatient population. Organizational model and preliminary results.

OBJECTIVE: To compare the efficacy of diet alone vs interdisciplinary therapy. METHOD: 256 women were divided into an interdisciplinary therapy group composed of 102 subjects and a control group composed of 154 subjects treated by means of diet alone. RESULTS: 21.56% of the interdisciplinary group did not come for the 2 check-ups compared with 49.35% of the diet group (p < 0.001). A weight loss of 5.88 kg and 4.18 kg for the interdisciplinary and the diet group was recorded 8 weeks after the start of the programme (second check-up). DISCUSSION: Interdisciplinary therapy is necessary to personalize treatment and satisfy the patient's desire and need for appropriate and effective management.

The three-factor eating questionnaire in the evaluation of eating behaviour in subjects seeking participation in a dietotherapy programme.

AIM: To evaluate the eating behaviour in normal-weight, overweight, and obese women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. METHODS: Thirty-seven obese, 42 overweight, and 14 normal-weight subjects, seen at an Italian university outpatient clinic, were asked to complete the Stunkard and Messick three-factor eating questionnaire (TFEQ). The TFEQ is designed to evaluate three different factors in eating behaviour: restraint, disinhibition, and hunger. Forty-eight mothers of children attending public primary schools (25 normal weight and 23 overweight) served as controls. RESULTS: Significantly altered scores of cognitive restraint were observed both in normal-weight and in overweight subjects of the outpatient clinic as compared with normal-weight and overweight control women. Outpatient clinic overweight women scored significantly higher in terms of disinhibition as compared with overweight control subjects. Among outpatient clinic subjects, overweight women showed higher scores of disinhibition but similar values of cognitive restraint as compared with outpatient clinic normal-weight subjects. In obese patients, the scores of disinhibition and hunger were higher than those observed in outpatient clinic normal-weight subjects, whereas values of cognitive restraint were significantly lower. As compared with outpatient clinic overweight women, obese subjects showed significantly lower values of cognitive restraint. CONCLUSIONS: Alterations in TFEQ results are a frequent feature in subjects seeking participation in programmes of weight reduction or ideal body weight achievement. This may reflect a possible impairment in eating behaviour.

Influence of carrier ligand NH hydrogen bonding to the O6 and phosphate group of guanine nucleotides in platinum complexes with a single guanine ligand.

Coordinated N,N',N"-trimethyldiethylenetriamine (Me3dien) has several possible configurations: two have mirror symmetry (R,S configurations at the terminal nitrogens) and the terminal N-Me's anti or syn with respect to the central N-Me (anti-(R,S) and syn-(R,S) isomers, respectively), and two are nonsymmetrical (R,R and S,S configurations at terminal nitrogens, rac denotes a 1:1 mixture of the two isomers). For each configuration, two Me3dienPtG atropisomers can be formed (anti or syn orientation of central N-Me and G 06, G = guanine derivative), and these can be observed since the terminal N-Me's decrease the rate of G rotation about the Pt-N7 bond. In symmetrical syn-(R,S)-Me3dienPtG derivatives with G = 9-EtG and 3'-GMP, the anti rotamer, which can form O6-NH H-bonds, was slightly favored over the syn rotamer but never more than 2:1. This anti rotamer is also favored by lower steric repulsion between the terminal N-Me's and G O6; thus, the contribution of O6-NH H-bonding to the stability of the anti rotamer could be rather small. With G = 5'-GMP, an O6-NH H-bond in the anti rotamer and a phosphate-NH H-bond in the syn rotamer can form. Only the syn rotamer was detected in solution, indicating that NH H-bonds to 5'-phosphate are far more important than to O6, particularly since steric factors favor the anti rotamer. Interconversion between rotamers was faster for syn-(R,S)- than for rac-Me3dien derivatives. This appears to be determined by a smaller steric impediment to G rotation of two "quasi equatorial" N-Me's, both on one side of the platinum coordination plane (syn-(R,S) isomer), than one "quasi equatorial" and one "quasi axial" N-Me on either side of the coordination plane (rac isomer).

The Eating Disorder Inventory in evaluation of impaired eating behaviour in subjects requesting nutritional consultation.

The present study evaluated impaired eating behaviour in women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. Forty-seven obese, 42 overweight and 14 normal-weight subjects, attending an Italian university outpatient clinic completed the Eating Disorder Inventory (EDI). Forty-eight mothers of primary school children (25 normal-weight and 23 overweight) were used as controls. The EDI consists of 8 subscales, 3 evaluating psychopathology related to eating disorders (drive for thinness, bulimia, body dissatisfaction) and 5 evaluating general psychopathology (intereoceptive awareness, ineffectiveness, maturity fears, perfectionism, interpersonal distrust). Significantly altered scores in the first three subscales were observed both in normal-weight and overweight outpatients compared to the controls. The overweight outpatients scored higher than the obese patients in terms of drive for thinness and bulimia and higher than the normal-weight women for terms of bulimia, body dissatisfaction and drive for thinness. The overweight controls scored significantly higher than the normal-weight controls in the first three subscales in the remaining subscales, mean values were also higher in the overweight group, though significance was only reached in the interpersonal distrust and interoceptive awareness subscales. Impaired eating behaviour is frequent in subjects seeking participation in weight reduction or ideal body weight achievement programmes.

Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC).d(GAGAGCGAGG).

The single-stranded oligonucleotide 5'-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl(2){E-HN = C(OMe)Me}(2)] (trans-EE) and subsequently annealed with its complementary strand 5'-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D proton NMR spectroscopy at 600 MHz. In agreement with previous studies by different techniques trans-EE was found to form a monofunctional adduct with the duplex involving the guanine residue. The modification by trans-EE has been found to induce only minor local distortion in the duplex geometry. Two key crosspeaks observed in the NOESY map corresponding to a close contact between G5-H8 and the methoxy and the methyl group, respectively, enabled us to dock the trans-EE complex with the duplex by geometry optimization. The results support the idea that the antitumor activity of trans-EE is related to lesion of DNA fundamentally different from that of cisplatin. Unexpectedly, the NOESY spectra indicated that at the high NaCl concentration used (0.2 M) the duplex was found to undergo slow deplatination. This was subsequently proved by HPLC. In a separate experiment on platination of the single strand in a salt free environment the HPLC analysis showed that the monofunctional adduct was not deplatinated, however, after 24 hours, additidnal minor isomers were detected.