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Biomedical subjects

Giuseppe Bifulco

Publications and source records attributed to Giuseppe Bifulco.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study.

BACKGROUND: A prospective, randomized, controlled study was performed to assess the efficacy of auto-crosslinked hyaluronic acid (ACP) gel to prevent the development of de-novo intrauterine adhesions following hysteroscopic surgery. METHODS: One hundred and thirty-two patients with a single surgically remediable intrauterine lesion (myomas, polyps and uterine septa, subgroups I-III) completed the study. Patients were randomized to two different groups: group A underwent hysteroscopic surgery plus intrauterine application of ACP gel (10 ml) while group B underwent hysteroscopic surgery alone (control group). The rate of adhesion formation and the adhesion score was calculated for each group and subgroup 3 months after surgery. RESULTS: Group A showed a significant reduction in the development of de-novo intrauterine adhesions at 3 months follow-up in comparison with the control group. Furthermore, the staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel. CONCLUSIONS: ACP gel significantly reduces the incidence and severity of de-novo formation of intrauterine adhesions after hysteroscopic surgery.

Adult↗
PubMed2004

Quantum mechanical calculations of NMR J coupling values in the determination of relative configuration in organic compounds.

[structure: see text] An approach relying on quantum mechanical calculations of proton-proton and proton-carbon J coupling values is proposed as a tool for assigning the relative configuration on chiral organic compounds. The method is suitable for carbon frameworks containing several adjacent stereogenic centers and may allow significant advances in the extensive use of spin-spin couplings in structural elucidation.

Journal Article↗
PubMed2004

Comparison of different theory models and basis sets in the calculation of 13C NMR chemical shifts of natural products.

The influence of the calculation method in mimicking experimental (13)C NMR chemical shifts of 15 low-polarity natural products singularly containing 10-20 carbon atoms was investigated by employing different quantum chemistry approaches and basis sets, both in the preliminary geometry optimizations and in the following single-point (13)C GIAO calculations of the NMR chemical shifts. The geometries of the involved species were optimized at the PM3, HF, B3LYP and mPW1PW91 levels whereas the (13)C NMR parameters were determined at the HF, B3LYP and mPW1PW91 levels. Different combinations of basis sets were also tested. The consistency and efficiency of the considered combinations of geometry optimizations and GIAO (13)C NMR calculations were thoroughly checked by the analysis of statistical parameters concerning computed and experimental (13)C NMR chemical shift values.

Biological Products↗
PubMed2004

Estrogen-progestogen induced hematocolpometra following allogeneic stem cell transplant.

OBJECTIVES: Gynecological manifestation of chronic graft-versus-host disease (cGVHD) has been invariably described in association with its extensive form. We have also observed it in a patient with the limited cGVHD form. DESIGN: We here describe our experience of gynecological complications in a population of 30 women who were followed up in a single center 12-120 months after allogeneic stem cell transplant (allo-SCT) due to hematological malignancies. All of them manifested premature ovarian failure because of the received treatments. RESULTS: Three out of 14 women who were affected by cGVHD developed hematocolpometra after estrogen + progestogen therapy (EPT) introduction, due to uterine and vaginal dystrophy and synecchiae. Extensive cGVHD, including dermal and mucosal localization, was present in two women while the third had only liver involvement. None of our patients had received radiation therapy or had a posttransplant history of infection. Local application of estrogens consistently improved the gynecological complication. However, vaginal synecchiae tended to relapse when local treatment was interrupted, despite no other apparent evidence of active cGVHD. CONCLUSIONS: All women with cGVHD should undergo gynecological examination before introducing EPT, to avoid unpleasant complication as hematocolpometra. Vaginal and cervical synecchiae should be treated with prolonged local treatments, and temporary use of continuous EPT regimens may be preferable in these women. Moreover, close monitoring by pelvic exam and ultrasonography is advisable during the initial cycles to detect any complication caused by possible intrauterine adhesions undetected during the previous gynecological examination.

Adolescent↗
PubMed2004

Tolaasins A--E, five new lipodepsipeptides produced by Pseudomonas tolaasii.

Pseudomonas tolaasii, the causal organism of brown blotch disease of Agaricus bisporus and of the yellowing of Pleurotus ostreatus, was shown to produce in culture tolaasin I (1), tolaasin II (2), and five other minor metabolites, tolaasins A, B, C, D, and E (3-7). These compounds were demonstrated to be important in the development of the disease symptoms. This paper reports on the structural elucidation, based essentially on NMR studies and MS spectra, and biological activity of the above lipodepsipeptides (3-7). All the above analogues showed differences in the peptide moiety, as observed in other lipodepsipeptides of bacterial origin, and maintained the beta-hydroxyoctanoyl phi chain at the N-terminus, except tolaasin A, in which the acyl moiety was a gamma-carboxybutanoyl phi moiety. Among the target microorganisms used (fungi, yeast, and bacteria) the Gram-positive bacteria were the most sensitive, although the antimicrobial activity appeared to be correlated to the structural modification in the different analogues. The structure-activity relationships of these toxins are discussed.

Agaricus↗
PubMed2004

Synthesis, conformational analysis, and cytotoxicity of new analogues of the natural cyclodepsipeptide jaspamide.

Three analogues of the natural bioactive cyclodepsipeptide jaspamide (3-5) were efficiently synthesized using a combination of solid and solution phase techniques. The preliminary design of the molecules has involved the rational substitution and/or simplification of the most critical structural features of the lead compound. The synthetic products were subjected to pharmacological assays, and the conformational properties were investigated by MM (molecular mechanics) and MD (molecular dynamics) calculations, to describe the potential pharmacophoric core responsible for the observed activities.

Antineoplastic Agents↗
PubMed2003

NMR structure of the (+)-CPI-indole/d(GACTAATTGAC)-d(GTCAATTAGTC) covalent complex.

We report the NMR solution structure of (+)-CPI-indole (CPI, 1,2,8,8a-tetrahydrocyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one), an agent belonging to the CC-1065/duocarmycin family of antitumor compounds. This (+)-CPI-indole structure is covalently bound to d(G(1)ACTAATTGTC(11))-d(G(12)TCAATTAGTC(22)), a synthetic DNA duplex containing a high-affinity binding site. The three-dimensional structure has been determined by several cycles of restrained molecular dynamics calculations with a total of 563 NMR-derived constraints, both in vacuo and by using the generalized Born solvent continuum model. In-depth analysis of the structure of this ligand-DNA complex led to a detailed knowledge of the bound state conformation of the CPI-indole, the most simplified agent related to CC-1065 and duocarmycins, the parent members of a family of extremely potent antitumor compounds. Comparison of the CPI-indole bound conformation with those previously found for (+)-duocarmycin SA (DSA), its unnatural enantiomer (-)-DSA, and the demethoxylated analogue (+)-DSI in their DNA complexes provided additional evidence of the tight correlation between the catalytic effect exerted by DNA on the alkylation reaction and the extent of angular twist between the two planar heteroaromatic subunits of these agents. Additionally, comparison of the structural features of the DNA-bound state of a "naked" ligand, such as CPI-indole, with those of various other duocarmycin agents provided useful information for the interpretation of the observed effects on chemical reactivity of the different substitution patterns at the hemispheres of these types of complex.

Antineoplastic Agents, Alkylating↗
PubMed2003

Effectiveness of autocrosslinked hyaluronic acid gel after laparoscopic myomectomy in infertile patients: a prospective, randomized, controlled study.

OBJECTIVE: To assess the efficacy of autocrosslinked hyaluronic gel in postsurgical adhesion prevention after laparoscopic myomectomy. DESIGN: Prospective, randomized, controlled study. SETTING: University of Naples "Federico II".Thirty-six infertile women with symptomatic myomas were randomly divided into two groups of 18 patients each. INTERVENTION(S): Laparoscopic myomectomy with subserous sutures or interrupted figure 8 sutures, with (group A) or without (group B) application of autocrosslinked hyaluronic acid (HA) gel. MAIN OUTCOME MEASURE(S): Rate of postsurgical adhesions at 60-90 days of follow-up. The rate of subjects who developed postoperative adhesions was significantly lower in group A in comparison with group B (27.8% vs. 77.8%). In both groups, the rate of adhesions was significantly higher in patients treated with interrupted figure 8 sutures than with subserous sutures. CONCLUSION(S): Autocrosslinked HA gel is a promising resorbable agent barrier for the reduction of postoperative adhesions after laparoscopic myomectomy. Moreover, the type of suture is a factor influencing the postsurgical adhesion formation.

Adult↗
PubMed2003

Serum leptin levels in patients with premenstrual syndrome treated with GnRH analogues alone and in association with tibolone.

OBJECTIVE: Leptin seems to regulate reproductive function and it has been hypothesised that its secretion may be induced by oestrogens. Changes in its levels has been advocated as a determinant in the pathogenesis of premenstrual syndrome (PMS). We evaluated serum leptin levels in patients affected by PMS and in controls to establish: (i) if induced hypoestrogenism has an impact on leptin concentrations; (ii) if the administration of tibolone modifies the effects of hypoestrogenism on serum leptin levels; and (iii) if the improvement in PMS symptomatology can be correlated to changes in serum leptin levels. DESIGN: Prospective, randomized study. PATIENTS: Twenty-eight women affected by PMS and 20 unaffected controls. Affected patients were randomly assigned to two groups to receive leuprolide acetate (3.75 mg intramuscularly) plus tibolone (2.5 mg/day) (group A; n = 14) or plus placebo (group B; n = 14), at the onset of the vasomotor symptoms. MEASUREMENTS: Serum leptin, oestradiol and progesterone levels, PMS signs and symptoms evaluated during a 2 months' pretreament period and after 2 months of therapy. RESULTS: No differences in leptin levels among the three groups and within the same group at all time evaluated were observed. Oestradiol and progesterone concentrations were significantly lower in all groups during treatment in comparison with pretreatment values. Before therapy, leptin levels were positively correlated both with oestradiol and progesterone in the follicular and luteal phase in all groups. This correlation was lost after treatment. All PMS patients showed a significant improvement of the symptomatology. CONCLUSIONS: Hypoestrogenism induced by GnRH analogues (GnRHa) does not seem to influence leptin levels in normal women and those with PMS, and the addition of tibolone does not impact on these levels. Because PMS symptomatology did significantly improve during treatment with GnRHa alone, or in associtation with tibolone, it is unlikely that changes in leptin levels could have an important role in the pathophysiology of PMS.

Adult↗
PubMed2003

Gonadal status in reproductive age women after haematopoietic stem cell transplantation for haematological malignancies.

BACKGROUND: Ovarian failure is a frequent complication occurring after haematopoietic stem cell transplantion (SCT), which is generally ascribed to radiation treatment and antiblastic alkylating agents. METHODS: Ovarian morphology and function were studied in reproductive age women 12-24 months after allogeneic SCT (n = 23) received from an HLA identical sibling, or autologous SCT (n = 22). Thirteen allo-transplanted women were suffering from chronic graft-versus-host disease (cGVHD). RESULTS: Menstrual cycles recovered in two and four women in the allo- and auto-SCT groups respectively, being associated with younger age and longer period elapsed from transplant. There was no difference in previous use of alkylating agents between allo- and auto-transplantation, while corticosteroid treatment was longer and more recent in the allo-SCT group. Significantly higher gonadotrophin levels and lower estradiol were seen in the combined group of patients than in controls. In allo-transplanted women, androgens were also significantly lower than in controls. Ovarian and uterine volumes were lower in patients than in controls, and in the allo- than in the auto-transplanted women. Within the allo-SCT group, endocrine function and ovarian and uterine volumes were significantly lower in the patients suffering from cGVHD. CONCLUSIONS: Ovarian failure in SCT recipients is likely to be caused principally by myelo-ablative treatments, but the condition of gonadal and androgen insufficiency can be worsened by an altered immunomodulation in allogeneic setting.

Adult↗
PubMed2003

Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study.

BACKGROUND: A prospective, randomized, controlled study was performed to assess the efficacy of auto-cross-linked hyaluronic acid (ACP) gel in preventing the development of intrauterine adhesions following hysteroscopic adhesiolysis. METHODS: Ninety-two patients with irregular menses and intrauterine adhesions referred to the Hysteroscopic Unit of the University of Naples "Federico II". Patients were randomized to two different groups. Group A were randomized to hysteroscopic adhesiolysis plus intrauterine application of ACP gel (10 ml) and group B were randomized to operative hysteroscopy alone (control group). Baseline adhesion scores were calculated for each patient and at 3 months after surgery. RESULTS: Group A showed a significant decrease in intrauterine adhesions at 3 months follow-up in comparison with the control group. Staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel. CONCLUSIONS: ACP gel significantly reduces the development of intrauterine adhesions postoperatively and its use is likely to be associated with a reduction of severe adhesions.

Adult↗
PubMed2002

Extension of the J-based configuration analysis to multiple conformer equilibria: an application to sapinofuranone A.

[structure: see text] A new strategy that extends the application of the J-based configuration analysis to systems characterized by multiple conformer equilibria is described and applied to sapinofuranone A (1), a phytotoxic molecule produced by three strains of Sphaeropsis sapinea. This method, based on a combination of computational techniques and NMR spectroscopy, uses ab initio calculations to predict a set of theoretical homo- and heteronuclear J values which can be compared against experimental NMR data.

Biological Factors↗
PubMed2002

Structure validation of natural products by quantum-mechanical GIAO calculations of 13C NMR chemical shifts.

Geometry optimization and GIAO (gauge including atomic orbitals) (13)C NMR chemical shift calculations at Hartree-Fock level, using the 6-31G(d) basis set, are proposed as a tool to be applied in the structural characterization of new organic compounds, thus providing useful support in the interpretation of experimental NMR data. Parameters related to linear correlation plots of computed versus experimental (13)C NMR chemical shifts for fourteen low-polar natural products, containing 10-20 carbon atoms, were employed to assess the reliability of the proposed structures. A comparison with the hybrid B3LYP method was carried out to evaluate electron correlation contributions to the calculation of (13)C NMR chemical shifts and, eventually, to extend the applicability of such computational methods to the interpretation of NMR spectra in apolar solutions. The method was tested by studying three examples of revised structure assignments, analyzing how the theoretical (13)C chemical shifts of both correct and incorrect structures matched the experimental data.

Biological Products↗
PubMed2002

Determination of the relative stereochemistry of flexible organic compounds by Ab initio methods: conformational analysis and Boltzmann-averaged GIAO 13C NMR chemical shifts.

Ab initio calculations at the Hartree-Fock level with full-geometry optimization using the 6-31G(d) basis set, and GIAO (gauge including atomic orbitals) (13)C NMR chemical shifts, are presented here as a support in the study of the stereochemistry of low-polar organic compounds having an open-chain structure. Four linear stereoisomers, fragments of a natural product previously characterized by experimental (13)C NMR spectra, which possesses three stereogenic centers, 11 carbon atoms, and 38 atoms in total, were considered. Conformational searches, by empirical force-field molecular dynamics, pointed out the existence of 8-13 relevant conformers per stereoisomer. Thermochemical calculations at the ab initio level in the harmonic approximation of the vibrational modes, allowed the evaluation, at 298.15 K, of the standard Gibbs free energy of the conformers. The (13)C NMR chemical shift of a given carbon atom in each stereoisomer was considered as the average chemical shift value of the same atom in the different conformers. The averages were obtained by the Boltzmann distribution, using the relative standard free energies as weighting factors. Computed parameters related to linear correlation plots of experimental (13)C chemical shifts versus the corresponding computed average data allowed us to distinguish among the four stereoisomers.

Journal Article↗
PubMed2002

Glucose regulates insulin mitogenic effect by modulating SHP-2 activation and localization in JAr cells.

The glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6 mm glucose (LG), proliferation and thymidine incorporation were induced by serum, epidermal growth factor, and insulin-like growth factor 1 but not by insulin. In contrast, at 25 mm glucose (HG), proliferation and thymidine incorporation were stimulated by insulin, serum, epidermal growth factor, and insulin-like growth factor 1 to a comparable extent, whereas basal levels were 25% lower than those in LG. HG culturing also enhanced insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal phosphorylations. These actions of glucose were accompanied by an increase in cellular tyrosine phosphatase activity. The activity of SHP-2 in HG-treated JAr cells was 400% of that measured in LG-treated cells. SHP-2 co-precipitation with IRS1 was also increased in HG-treated cells. SHP-2 was mainly cytosolic in LG-treated cells. However, HG culturing largely redistributed SHP-2 to the internal membrane compartment, where tyrosine-phosphorylated IRS1 predominantly localizes. Further exposure to insulin rescued SHP-2 cytosolic localization, thereby preventing its interaction with IRS1. Antisense inhibition of SHP-2 reverted the effect of HG on basal and insulin-stimulated insulin receptor and IRS1 phosphorylation as well as that on thymidine incorporation. Thus, in JAr cells, glucose modulates insulin mitogenic action by modulating SHP-2 activity and intracellular localization.

3T3 Cells↗
PubMed2002

Menstrual status and serum leptin levels in anorectic and in menstruating women with low body mass indexes.

OBJECTIVE: To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI. DESIGN: Prospective study. SETTING: University clinics. PATIENT(S): Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI <18 kg/m(2) (group B), and 20 normal controls. MAIN OUTCOME MEASURE(S): Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E(2), PRL, and TSH levels. INTERVENTION(S): None. RESULT(S): Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin. CONCLUSION(S): A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.

Adult↗
PubMed2002

Renieramide, a cyclic tripeptide from the Vanuatu sponge Reniera n. sp.

The polar extract of the Vanuatu sponge Reniera n. sp., which showed immunomodulating activity in preliminary tests, was found to contain a cyclic tripeptide, which we named renieramide (1). This metabolite is identical to a synthetic derivative mentioned in a patent concerning the preparation of cyclic peptides of the OF4949 family of anticancer agents. We describe here the first isolation of this metabolite from natural sources and its complete characterization by spectroscopic and chemical approaches. Renieramide (1) possesses a 17-membered cyclic side-chain-linked biphenyl ether skeleton, typical of the class that includes the natural products OF4949 I-IV, K13, and eurypamides. A tridimensional model of 1, obtained by NMR restrained molecular mechanics and dynamics, is also presented.

Adjuvants, Immunologic↗