Novel drug delivery systems for natural extracts: The case study of Vitis Vinifera extract-SiO2 nanocomposites.

Ball Milling technique has been used to prepare for the first time Vitis Vinifera extract-silica nanocomposites (VV-SiO2 NCs), which combine the pharmacological effects of the extract with the effectiveness of silica as drug delivery system and active component in the treatment of wound healing. Different contents (1.0, 9.0 and 33.0 wt%) of Vitis Vinifera ethanolic extract were loaded into the silica matrix by grinding the extract with fumed silica using a planetary mill apparatus. The effect of the starting mixture composition and milling time on the final products was examined. The efficiency of the milling process was studied by X-ray Powder Diffraction, Nuclear Magnetic Resonance, and Infrared Spectroscopy, indicating that the natural extract was not affected by the increasing of the milling time. The successful loading of the extract was demonstrated by Nitrogen adsorption/desorption measurements, which showed a decrease in the SSA and pore volume of the silica with the increasing of the extract amount. Morphology of the nanocomposites, investigated by Scanning Electron Microscopy, showed an increased agglomeration in the nanocomposites with the increment of the VV extract amount. Studies on the total phenol quantification and antioxidant activity of the natural extract before and after incorporation in the silica matrix were also carried out. The obtained results indicate that the milling process does not alter the VV extract components, which result to be embedded in the silica matrix. An increase of the antioxidant activity with the increment of the extract amount in the nanocomposites, up to values comparable to the pure VV extract, was also observed.

Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: an observational study.

PURPOSE OF INVESTIGATION: To evaluate the effect of soy isoflavones and inulin (SII) on hot flushes (HF) and quality of life in a clinical setting, the authors conducted an observational study. MATERIALS AND METHODS: The authors performed an observational, prospective, multicentric study on women in peri-/post-menopause treated or untreated with a product present on the Italian market, consisting in a mixture of calcium (500 mg), vitamin D3 (300 IU), inulin (3 g) and soy isoflavones (40 mg). RESULTS: A total of 135 patients, 75 (55.6%) in the SII group and 60 (44.4%) in the untreated group entered the study. After three months, the mean number of HF declined of 2.8 (SD 3.7) in the SII group and 0.0 in the untreated one. The corresponding values after six months were -3.7 (SD 2.7) in the SII group and -0.9 (SD 5.3) in the control group (p = 0.02). CONCLUSION: This observational trial suggests a possible beneficial effect of a dietary soy supplement containing 40 mg of isoflavone/day plus inulin in the management of menopausal symptoms such as hot flashes.

Tissue characterization using mean gray value analysis in deep infiltrating endometriosis.

OBJECTIVES: To investigate differences in tissue characterization using three-dimensional sonographic mean gray value (MGV) between retrocervical and rectosigmoid deeply infiltrating endometriosis, and to assess intra- and interobserver concordance in MGV quantification. METHODS: In this retrospective study, stored ultrasound volumes from 50 premenopausal women (mean age, 32 years) with 57 histologically confirmed nodules of deep endometriosis were retrieved from our database for analysis. A single experienced operator had acquired all volumes. For each nodule, the MGV was evaluated using virtual organ computer-aided analysis (VOCAL) software with semiautomated sphere-sampling (1 cm3) from the central part of the nodule. In these patients the MGV was also quantified from the myometrium of the fundal part of the uterus. In addition, two observers calculated the MGV in a subset of 24 volumes in order to quantify inter- and intraobserver agreement using intraclass correlation coefficients (ICC). RESULTS: Mean MGV was significantly higher in rectosigmoid nodules (n = 34) than in nodules with a retrocervical location (n = 23) (23.863 vs. 17.705; P < 0.001). MGV of the myometrium was significantly higher in comparison with that of nodules in both locations (P < 0.001 for both). Intra- and interobserver measurement reproducibility was excellent (ICC > 0.95). CONCLUSIONS: Retrocervical and rectosigmoid endometriotic nodules display significantly different MGVs. Measurement of MGV is highly reproducible and its clinical value in the diagnosis and assessment of distribution of deep endometriosis should be assessed in future studies.

Low androgenization index in elderly women and elderly men with Alzheimer's disease.

The authors investigated whether testosterone levels and testosterone availability differ between older lean subjects with and without Alzheimer's disease (AD). Sex hormone binding globulin (SHBG) and estradiol levels were higher, whereas the free androgenization index (FAI) was lower, in lean subjects with AD than in lean subjects without AD. Factors involved in the increase of SHBG secretion could have an important role in the lower testosterone availability of subjects with AD.

Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel.

Oral contraceptives slightly deteriorate insulin sensitivity. The present study investigated whether they may further unbalance the glucose metabolism of lean women with polycystic ovary syndrome (PCOS). Women with PCOS were assigned to receive for 6 months the biphasic association of 40/30 micro g ethinyl estradiol (EE) and 25/125 micro g desogestrel (DSG; n = 10) or the monophasic association of 35 micro g EE and 2 mg cyproterone acetate (CPA; n = 10). Glucose tolerance was investigated by an oral glucose tolerance test (OGTT). Glucose utilization dependent [insulin sensitivity (SI)] or independent (Sg) of insulin was investigated by the minimal model method applied to a frequently sampled iv glucose tolerance test. EE/DSG increased the response of C peptide to OGTT (1413 +/- 113 vs. 2053 +/- 213 area under the curve; P < 0.009) and the C peptide/insulin ratio (0.085 +/- 0.01 vs. 0.134 +/- 0.01 area under the curve; P < 0.003). It also increased the Sg (0.026 +/- 0.002 vs. 0.034 +/- 0.003; P < 0.04) and decreased the SI (2.40 +/- 0.26 vs. 1.68 +/- 0.27; P < 0.01). EE/CPA did not modify responses to OGTT of glucose, insulin, C peptide, or C peptide/insulin ratio. It did not modify Sg and significantly increased SI (1.47 +/- 0.38 vs. 3.27 +/- 0.48; P < 0.04). The present study indicates that EE/CPA improves SI, whereas EE/DSG impairs SI, but improves insulin clearance. The long-term metabolic effects of these two compounds on women with PCOS require further investigations.

[Clinical and echocardiographic evaluation of thalassemic cardiomyopathy]. / Valutazione clinica ed ecocardiografica della cardiomiopatia talassemica.

To evaluate the reliability of the echocardiographic examination in assessment of adult patient with thalassemia major, in comparison with clinical, electrocardiographic and/or chest x ray exams, 103 patients with thalassemia major, mean age 20 years (range 14 to 30 years), were studied and compared with 30 age matched normal subjects. All patients were receiving transfusions regularly to maintain hemoglobin levels above 11 g/dl and subcutaneous infusions of desferrioxamine (about 40 mg/kg/day) to reduce hemosiderosis. The patients were divided into three groups according to their cardiac impairment, deduced by clinical history, electrocardiography (ECG) and/or chest x ray. Group I (36 patients) showed no signs or symptoms of cardiac impairment. Group II (38 patients) had only signs of cardiac impairment by ECG and/or chest x ray. Group III (29 patients) had both symptoms and signs of cardiac failure. In comparison to normal controls, Group I showed an increase in left ventricular (LV) dimension (EDD) and mass (p < 0.001), Group II and III showed a decrease in LV fractional shortening (FS; p < 0.001) too. In comparison to Group I, Group II showed a decrease in LV FS (p < 0.05), Group III showed an increase in LV EDD and mass (p < 0.001) too. In comparison to Group II, Group III showed an increase in LV EDD and mass (p < 0.001), and a decrease in LV FS (p < 0.001). In conclusion, echocardiographic examination appears a tool more reliable than clinical, electrocardiographic and/or chest x ray examination in assessment of adult patient with thalassemia major.(ABSTRACT TRUNCATED AT 250 WORDS)

[Preoperative levels of CA 125 and risk factors in adenocarcinoma of the endometrium]. / Livelli preoperatori del CA 125 e fattori di rischio nell'adenocarcinoma dell'endometrio.

Preoperative serum CA 125 levels were measured in 61 patients with various FIGO stage endometrial adenocarcinoma and they were compared with stage of disease, grading and pelvic lymph nodes involvement. Serum CA 125 levels in excess of 35 U/ml were detected in 19 patients (31.1%): circulating levels exceeding 65 U/ml were also found in 15 patients (24.5). Rising concentrations were associated with increasing stages. Grading and lymph nodes involvement were correlated with the presence of elevated serum levels (more than 65% for grade two or three and more than 80% in patients with positive lymph nodes). Preoperative high concentrations of CA 125 suggest the presence and the probability of advanced endometrial cancer. The cases with elevated CA 125 serum levels seems to be a higher risk for extrauterine tumor progression and lymphatic space invasion: the preoperative presence of the antigen imposes an accurate intraoperative surgical staging and a careful follow-up for preventing recurrence or metastases.

Progesterone and LH variations after LH-RH administration in the luteal phase of the menstrual cycle.

We have investigated the pituitary and luteal responses to LH-RH and their related changes. 11 normal women were studied during the luteal phase (day +4/+11). Blood samples were collected every 15 min for a basal period of 180 and 120 min after the intravenous administration of 25 micrograms of LH-RH. Progesterone (P) and LH were assayed by radioimmunoassay. Data were analyzed as maximum peak and its percent increase (delta max), integrated secretory area (ISA) and percent increase of ISA (delta A) in respect to basal values for both P and LH. LH-RH elicited a secretory response of both hormones in all cases. ISA of LH was significantly greater after LH-RH administration in respect to basal values (p less than 0.001) and delta max accounted to 475 +/- (SE) 36% of the basal concentration. Luteal responsiveness varied from about 115-130% to more marked increments. ISA of P differed from basal to stimulated conditions (p less than 0.05) and delta max was 166 +/- (SE) 14%. The analysis of temporal relationship between P and LH secretion showed that LH promptly rose after LH-RH, while the enhancement of P plasma levels occurred within 31 +/- 19 min after LH rise. Then P levels reached a plateau, values of which were statistically different from those observed before LH-RH administration. In two cases where luteal function was blunted or absent, in spite of marked increments of LH, P secretion did not occur. These data are consistent with the presence of close relationships between hypothalamic, pituitary and luteal functions and strengthen the contention about the usefulness of LH-RH during luteal phase for the lifespan and maintenance of corpus luteum.

Pulsatile Gn-Rh induced ovulatory cycles: echographic and endocrine aspects.

Five patients with primary hypogonadotrophic amenorrhea were treated for the induction of ovulation with I.V. pulsatile Gn-Rh doses ranging from 2.5 to 12.5 micrograms/90 min) for 15 cycles. Ovulation occurred during Gn-Rh treatment in 7 cycles (A) or after i.m. HGC administration (5,000-10,000 IU) (B = 6) (ovulation rate = 86%). Four pregnancies (A = 2; B = 2) were obtained (in one case there was a twin pregnancy). Echographic and endocrine patterns were evaluated. Ovulatory follicular diameter was 18.3 +/- 6.0 mm, no difference between A and B (21.8 +/- 5.6 and 16.0 +/- 5.1 mm, respectively) was observed. In addition E2 preovulatary plasma levels were similar in the two groups examined (334 +/- 131 and 300 +/- 89 pg/ml, respectively). Also endocrine and echographic profiles of conceptive (C) and non conceptive (NC) cycles were similar. Furthermore all doses resulted effective in determining the ovarian response and no difference was found at different dosage used. It is concluded that pulsatile GnRh is a "physiological" way of inducing ovulation in PHA patients. By analysis of the present data we consider it advisable to induce ovulation by the enhancement of the endogenous LH peak which occurs during Gn-Rh administration (A group) and then periodic injections of HCG can be used for maintaining the luteal function.