Design, synthesis, and conformational analysis of 3-cyclo-butylcarbamoyl hydantoins as novel hydrogen bond driven universal peptidomimetics.

A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was synthesized by a regioselective multicomponent domino process followed by easy coupling reactions. Calculations, NMR studies and X-ray analysis show that these scaffolds are able to project their side chains similar to common secondary structures, such as the α-helix and ß-turn, with favourable enthalpic and entropic profiles.

Shortened interval of long-acting octreotide administration is effective in patients with well-differentiated neuroendocrine carcinomas in progression on standard doses.

BACKGROUND: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited antiproliferative effects. AIM: The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations (21 days) in WDNET patients with progressive disease at standard-dose interval. SUBJECTS AND METHODS: Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled. Clinical, biological, and objective tumor response was evaluated after LAR 30 mg every 21 days. Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days. RESULTS: The treatment with LAR 30 mg every 21 days resulted in complete and partial control of clinical symptoms in 40% and 60% of cases, respectively. Circulating neuroendocrine markers were significantly decreased in 30% of cases. A stabilization of disease was obtained in 93% and objective response in 7%. The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the standard one (30 vs 9 months, p<0.0001). The treatment was safe and well tolerated. CONCLUSIONS: The shortened schedule of LAR administration was able to re-institute control of clinical symptoms, to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a standard schedule treatment.

3D-Structure of the interior fusion peptide of HGV/GBV-C by 1H NMR, CD and molecular dynamics studies.

In this work, we present a structural characterization of the putative fusion peptide E2(279-298) corresponding to the E2 envelope protein of the HGV/GBV-C virus by (1)H NMR, CD and MD studies performed in H(2)O/TFE and in lipid model membranes. The peptide is largely unstructured in water, whereas in H(2)O/TFE and in model membranes it adopts an helical structure (approximately 65-70%). The partitioning free energy DeltaG ranges from -6 to -7.5 kcal mol(-1). OCD measurements on peptide-containing hydrated and oriented lipid multilayers showed that the peptide adopts a predominantly surface orientation. The (1)H NMR data (observed NOEs, deuterium exchange rates, Halpha chemical shift index and vicinal coupling constants) and the molecular dynamics calculations support the conclusions that the peptide adopts a stable helix in the C-terminal 9-18 residues slightly inserted into the lipid bilayer and a major mobility in the amino terminus of the sequence (1-8 residues).

A novel route to the vinyl sulfide nine-membered macrocycle moiety of Griseoviridin.

The synthetic potentialities of cerium(III) chloride are demonstrated by the synthesis of a nine-membered ring heterocycle component of Griseoviridin (3) in optically active form. The key step involves the stereospecific formation of the alpha-carbalkoxy alkenyl sulfide moiety using a combination system of cerium(III) chloride heptahydrate and sodium iodide.

[Role of mammography in women under 35 years of age]. / Ruolo della mammografia nelle femmine al di sotto di 35 anni.

The detection of breast cancer in women under 35 is quite an uncommon event, accounting only for 3.2-3.4% of all breast cancers. To determine the indications for mammography in women under 35, the authors correlated clinical, mammographic, and US findings with fine-needle aspiration/surgical biopsy and follow-up results in 1040 symptomatic women examined at the Center of Senology of the Institute of Radiology-University of Perugia, Italy, from 1984 to June 1990. Of 1040 women, 482 (41.6%) had normal findings; benign disease was diagnosed in 558 (53.7%) cases, and malignant disease in 49 (4.7%). Mammography was very useful to diagnose malignancy in palpable breast lesions, as well as to suggest the need for biopsy, to detect metachronous cancers and to define lesion sizes. In inflammatory process--e.g., mastitis and abscesses--both mammography and US were capable of evaluating the real extent of the process, as well as its remission after therapy. Galactography had a specific role in the evaluation of the mammary duct and demonstrated intraductal pathologic conditions. In the authors' experience, mammography never showed occult breast cancers in women with no palpable breast lesions or hematic nipple discharge.

[Preoperative localization using a bidimensional mammographic technique of non-palpable lesions of the breast]. / Localizzazione preoperatoria con tecnica mammografica bidimensionale di lesioni mammarie non palpabili.

It is widely known how the early diagnosis and treatment of breast cancer may lead to better prognosis. When a non-palpable breast lesion detected with mammography is correctly localized with fine-needle biopsy under X-ray guidance, the surgeon can easily remove the lesion while preserving normal breast tissue. In such cases, histology is also possible. The authors describe an easy bidimensional technique for the preoperative localization of occult nonpalpable breast lesions with a fine-needle. The procedure is feasible also with out-of-date equipment and does not cause any discomfort to the patients. It should be performed on all women with mammographic suspicion of non-palpable breast lesion. From January through December 1989 the authors performed 64 preoperative fine-needle biopsies of clinically-occult breast lesions. The presence of a lesion associated with microcalcifications was found to be indicative of malignancy more often than in the case of microcalcifications or lesions alone. Of 64 cases, histology demonstrated malignancy in 31 patients.

[Radiotherapy of testicular seminoma. Stages I and II A, B]. / Radioterapia del seminoma testicolare. Stadio I e II A, B.

From June 1977 through June 1987, 46 patients (36 evaluable) affected by stage I and II non-bulky testicular seminoma were treated with postoperative telecobaltotherapy (TCT). In stage I seminomas, radiotherapy was extended to the omolateral iliac and the para-aortic areas (total dose: 30 Gy over 4 weeks). In stage II seminomas, the subdiaphragmatic lymph nodes were irradiated with 40-45 Gy over 5-6 weeks; after an interval of one month the subdiaphragmatic lymph nodes were irradiated again with a total dose of 25 Gy over 3.5 weeks. Minimal follow-up lasted two years and maximum ten years (average: 5.5). Two (5.5%) recurrences occurred, but salvage radiotherapy and salvage chemotherapy respectively allowed a complete permanent remission. One patient died from a different neoplasia with no evidence of testicular involvement. The 5-year actuarial survival is 96.6 +/- 3.4. In 20% of the patients the side effects were nausea and/or vomiting, easily controlled. No late complications were observed.

Effect of dexamethasone on nitrogen metabolism in brain-injured patients.

A randomized prospective clinical trial was conducted to determine the influence of dexamethasone therapy on nitrogen metabolism in patients with isolated head trauma without any pathologies. One group of 12 patients was not given steroids (groups NS). To the 12 patients of the second group, a dose of 0.36 mg/kg/day of dexamethasone was administered for the first nine days of stay (group S) in hospital. At the beginning of the study, between the two groups, there were no differences in age, sex, Glasgow Coma Scale Score, type of injury. In order to avoid bias, phenytoin, barbiturates and muscle-relaxant drugs were not given and the same caloric and protein intake was prefixed for both groups. The urea excretion, nitrogen output, nitrogen balance and cumulative nitrogen balance were not statistically different in the two groups throughout the period of study. Similar were also weight losses, blood glucose, blood urea nitrogen, albumin and creatinine levels. The outcome, evaluated at 3 months, was also similar. The incidence of sepsis, pulmonary and urinary infections, gastric reflux duration and quantity, was not higher in the steroid group compared with non-steroid treated patients.