A promising eco-sustainable wound dressing based on cellulose extracted from Spartium junceum L. and impregnated with Glycyrrhiza glabra L extract: Design, production and biological properties.

Glycyrrhiza glabra extract is widely known for its antioxidant and anti-inflammatory properties and can improve the wound healing process. The aim of this work was to shorten the time of the healing process by using an eco-sustainable wound dressing based on Spanish broom flexible cellulosic fabric by impregnation with G. glabra extract-loaded ethosomes. Chemical analysis of G. glabra extract was performed by LC-DAD-MS/MS and its encapsulation into ethosomes was obtained using the ethanol injection method. Lipid vesicles were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In vitro release studies, biocompatibility, and scratch test on 3T3 fibroblasts were performed. Moreover, the structure of Spanish broom dressing and its ability to absorb wound exudate was characterized by Synchrotron X-ray phase contrast microtomography (SR-PCmicroCT). Ethosomes showed a good entrapment efficiency, nanometric size, good stability over time and a slow release of polyphenols compared to the free extract, and were not cytotoxic. Lastly, the results revealed that Spanish broom wound dressing loaded with G. glabra ethosomes is able to accelerate wound closure by reducing wound healing time. To sum up, Spanish broom wound dressing could be a potential new green tool for biomedical applications.

Wild rats as urban detectives for latent sources of asbestos contamination.

Based on a large body of evidence asbestos minerals have been classified as carcinogens. Despite the Italian ban on asbestos in 1992 and the subsequent remediation activities, latent sources of contamination may still represent a hazard where asbestos were particularly used. Using wild rats as sentinel animals, this study aimed at uncovering sites with the greatest potential for non-occupational exposure to asbestos in the city of Casale Monferrato (Piedmont Region, Italy), where the largest Italian manufacturing plant of asbestos-cement had been active. During the study period (2013-2015) a total of 40 wild rats were captured from 16 sampling capture points. The lungs of wild rats have been investigated by using scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS). The SEM-EDS detected the presence of asbestos fibers (tremolite/actinolite, amosite, and chrysotile) in rats' lungs from 11 sampling points. The hypothetical rats' home-range and the observed site-specific concentration of asbestos fibers per gram of dry lung tissue were used to identify areas to be targeted by additional search of latent sources of asbestos. In conclusion, our results showed that the use of wild rats as sentinel animals may effectively integrate the strategies currently in use to reduce the exposure to asbestos.

Multifactorial analysis of the stochastic epigenetic variability in cord blood confirmed an impact of common behavioral and environmental factors but not of in vitro conception.

Background: An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted. This study aims to evaluate the effect of ART and other common behavioral or environmental factors associated with pregnancy on stochastic epigenetic variability using a multivariate approach. Results: DNA methylation levels of cord blood from 23 in vitro and 41 naturally conceived children were analyzed using the Infinium HumanMethylation450 BeadChips. After multiple testing correction, no statistically significant difference emerged in the number of cord blood stochastic epigenetic variations or in the methylation levels between in vitro- and in vivo-conceived babies. Conversely, four multiple factor analysis dimensions summarizing common phenotypic, behavioral, or environmental factors (cord blood cell composition, pre or post conception supplementation of folates, birth percentiles, gestational age, cesarean section, pre-gestational mother's weight, parents' BMI and obesity status, presence of adverse pregnancy outcomes, mother's smoking status, and season of birth) were significantly associated with stochastic epigenetic variability. The stochastic epigenetic variation analysis allowed the identification of a rare imprinting defect in the locus GNAS in one of the babies belonging to the control population, which would not have emerged using a classical case-control association analysis. Conclusions: We confirmed the effect of several common behavioral or environmental factors on the epigenome of newborns and described for the first time an epigenetic effect related to season of birth. Children born after ART did not appear to have an increased risk of genome-wide changes in DNA methylation either at specific loci or randomly scattered throughout the genome. The inability to identify differences between cases and controls suggests that the number of stochastic epigenetic variations potentially induced by ART was not greater than that naturally produced in response to maternal behavior or other common environmental factors.

Nordic walking increases circulating VEGF more than traditional walking training in postmenopause.

OBJECTIVES: Nordic walking (NW) is widely practiced by postmenopausal women. Its effects are peculiar owing to the involvement of more muscle groups than in traditional walking training (WT). Since mechanical load promotes secretion of vascular endothelial growth factor (VEGF) from both skeletal muscle and muscle endothelium, the aim of the study was to compare the effect of NW and WT on VEGF levels. METHOD: Thirty postmenopausal women were randomly assigned to NW or WT. Both groups trained 40-50 min/day, three times per week, at a mean intensity of 12 on a 15-category scale of the ratings of perceived exertion. Since VEGF is also released from adipocytes, anthropometric parameters were assessed. RESULTS: NW increased circulating VEGF more than WT (p = 0.041). Furthermore, both study groups exhibited an average decrease in weight (p = 0.023), body mass index (p = 0.024), hip circumference (p = 0.001), and arm fat index, although WT participants had higher values for this index at baseline (p < 0.001) and thus exhibited a greater net decrease compared with the NW participants (p < 0.011). CONCLUSIONS: These data imply that NW increases the level of circulating VEGF more than does traditional walking when the intensity of training is equivalent.

Natural position of the head: review of two-dimensional and three-dimensional methods of recording.

Both the correct position of the patient's head and a standard system for the acquisition of images are essential for objective evaluation of the facial profile and the skull, and for longitudinal superimposition. The natural position of the head was introduced into orthodontics in the late 1950s, and is used as a postural basis for craniocervical and craniofacial morphological analysis. It can also have a role in the planning of the surgical correction of craniomaxillofacial deformities. The relatively recent transition in orthodontics from 2-dimensional to 3-dimensional imaging, and from analogue to digital technology, has renewed attention in finding a versatile method for the establishment of an accurate and reliable head position during the acquisition of serial records. In this review we discuss definition, clinical applications, and procedures to establish the natural head position and their reproducibility. We also consider methods to reproduce and record the position in two and three planes.

Which cephalometric analysis for maxillo-mandibular surgery in patients with obstructive sleep apnoea syndrome?

Maxillo-mandibular advancement MMA is considered an efficacious treatment for patients affected by severe obstructive sleep apnoea syndrome (OSAS). Even though OSAS improvement is the main goal of MMA, excessive maxillo-mandibular protrusion should be avoided to guarantee pleasant postoperative facial aesthetics. In order to attain such a result, the amount of MMA should be planned preoperatively by both aesthetic and cephalometric analyses. Steiner and Delaire cephalometric analyses are commonly used in the preoperative planning of orthognatic surgery for dentofacial deformities, however controversies still exist about the basis and postoperative aesthetic results of such cephalometric analyses in OSAS patients candidate for MMA. Forty-eight patients affected by severe OSAS were submitted to MMA. Pre- and post-operative Steiner and Delaire cephalometric tracings were assessed in each subject. For Steiner analysis, the variation in the SNA and SNB angles was measured, while for Delaire tracings the variation in the C3/FM-CPA and C3/FM-Me angles was assessed. Mean MMA was 6.9 + 3.8 mm for the maxilla and 13.6 + 5 mm for the mandible. After surgery, an improvement of the apnoea-hypopnoea index was recorded (40.47 + 7.64 preoperative vs. 12.56 + 5.78 postoperative). In all patients, both cephalometric analyses showed presurgical bimaxillary retrusion. After surgery, the mean value of Steiner's SNA angle increased from 78.18° to 85.58° (p < 0.001), while mean Delaire's C3/FM-CPA angle increased from 81.19° to 89.71° (p < 0.001). The mean value of Steiner's SNB angle increased from 74.33° to 80.73° (p < 0.001), while Delaire's C3/FM-Me angle increased from 80.10° to 87.29° (p < 0.001). Postoperatively, both the maxilla and mandible were in a more protrusive position (p < 0.001) according to Steiner analysis compared with Delaire tracing. Basing MMA on Delaire cephalometric analysis leads to an increased advancement of the maxillo-mandibular complex than Steiner tracing. The consequences of this aspect on facial aesthetics should be considered during surgical planning and preoperative informed consent in OSAS patients candidate for MMA.

Lifestyle and high density lipoprotein cholesterol in postmenopause.

OBJECTIVES: Menopause is characterized by hormonal and metabolic changes. These are linked to increased risk of cardiovascular disease, for which low blood plasma levels of high density lipoprotein (HDL) cholesterol are an independent risk factor. The present study investigated variables linked with basal plasma HDL cholesterol levels and the effects of aerobic training, on their variations, in 40 postmenopausal women. METHODS: We assessed body composition, dietary habits and maximal aerobic capacity of participants. Characteristics of daily physical activity and plasma lipoproteins were measured. The women walked on 4 days/week, for 14 weeks, at moderate intensity, and they were grouped according to the resulting tertiles of basal plasma HDL cholesterol levels. RESULTS: Logistic regression analysis showed that waist-to-hip ratio and number of daily bouts of moderate-intensity physical activity, held for at least 10 consecutive minutes (B10m/day), are predictive variables of basal plasma HDL cholesterol levels. After the training period, the first and second tertiles increased plasma HDL cholesterol levels, while the third tertile decreased plasma HDL cholesterol levels. The tertiles showed different remodelling of spontaneous physical activity: the third tertile reduced B10m/day, while the others did not. CONCLUSIONS: This study provides knowledge about the relationships of plasma HDL cholesterol levels with characteristics of physical activity. Furthermore, it shows that physical exercise engagement can result in negative compensation of spontaneous physical activity that could counteract or reduce the positive effects of the aerobic training on plasma HDL cholesterol levels.

Characteristics of spontaneous physical activity and executive functions in postmenopause.

AIM: Executive functions are susceptible to age-related changes, and menopause has also been shown to be linked with their decline. The aim of the present study was to investigate the variables related to executive functions in postmenopausal women not involved in controlled dietary and physical exercise programs and without hormone-replacement therapy. METHODS: Fifty-seven women (58.39 ±4.16 yr) were investigated for their medical history, blood lipids, insulin resistance (HOMA-IR), body composition, blood pressure, executive functions (Digit Span and Trail Making tests), maximal aerobic capacity, dietary habits, and spontaneous physical activity. RESULTS: Cluster analysis performed on the basal data of the Digit Span scores and Trail Making tests identified two subgroups: Group A (N.=24) that showed better executive functions than Group B (N.=33). Although these subgroups differed across several variables of body composition, plasma lipids, dietary habits, spontaneous physical activity, aerobic fitness, and insulin resistance, logistic regression models showed B10m/die as the only predictive variable for subgroup membership. CONCLUSION: In the absence of a physical exercise program, the knowledge of how spontaneous physical activity is organized (B10m/die) is important for executive functions of post-menopausal women. It is the specific moderate to intense physical activity characteristic of B10m/die, rather than generic physical activity, that seems to determine the maintenance or attainment of cognitive health through body movement.

Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects.

OBJECTIVE: Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features. DESIGN: To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m(-2)) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m(-2)), overweight (OW-SAT, BMI: 27.65±0.2 kg m(-2)) and obese patients, according to BMI classes (OB1-SAT: 30 > or = BMI < or = 34.9, OB2-SAT: 35 > or = BMI < or = 39.9, OB3-SAT: BMI > or = 40). SUBJECTS AND METHODS: A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques. RESULTS: Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis. CONCLUSIONS: Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear.

Orthognathic surgery for the complete rehabilitation of Moebius patients: principles, timing and our experience.

Moebius syndrome is a rare disorder found in approximately 1/100,000 neonates and the treatment of facial palsy is now well established worldwide and consists of free-muscle transplants reinnervated with motor nerves. Dentofacial deformities are often detected in Moebius patients, and different degrees of micrognathia are often present, particularly in patients with complete expressions of Moebius syndrome. However only two published reports have described the surgical treatment of such anomalies in these patients; in both cases, the suggested approach consisted of orthognathic surgery followed by soft-tissue management. In this paper we discuss the indications and correct timing of orthognathic surgery and suggest to perform facial animation at an early age and then to wait for the completion of maxillofacial skeletal growth before performing orthognathic surgery. Finally, facial animation should precede orthognathic surgery in adult patients to prevent lower lip deformities and to ensure more predictable and satisfactory results.

The nicotinic acetylcholine receptor α7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss.

BACKGROUND: It is known that cholinergic anti-inflammatory reflex regulates inflammation in peripheral tissues. Nicotinic acetylcholine receptors (nAChRs) are mediators of this anti-inflammatory pathway and also non-neuronal cells express functional nAChrs. A role for α7-subtype acetylcholine cholinergic receptor (α7nAChR) in insulin sensitivity improvement has already been shown in rodents both in vivo and in vitro. However, no data are available on α7nAChR expression in human adipocytes. OBJECTIVE: To investigate the expression and protein content of α7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes. DESIGN: A total of 39 SAT biopsy specimens obtained from obese and normal-weight subjects were used to assess α7nAChR messenger RNA levels and to stimulate α7nAChR with a specific agonist and antagonist in vitro. Additional SATs from eight non-diabetic obese subjects were also studied, before and after a 3-month lifestyle intervention. RESULTS: α7nAChR expression was significantly lower in the SAT of obese subjects compared with that of normal-weight subjects. In mature adipocytes isolated from morbidly obese subjects (body mass index > 40 kg m(-2)), α7nAChR expression was 75% lower compared with adipocytes from normal-weight subjects. In adipocytes of obese subjects, α7nAChR was downregulated also at protein level. In eight non-diabetic obese subjects, a lifestyle intervention (3 months of diet and physical activity) induced a significant weight loss and an increase in α7nAChR SAT expression. In vitro stimulation of adipocytes with the specific α7nAChR agonist PNU282987 induced a significant anti-inflammatory effect. Furthermore, a similar downregulation of the inflammatory profile, associated with a significant increase in α7nAChR protein level, was observed after genistein stimulation. CONCLUSIONS: These results provide evidence that α7nAChR expression levels are significantly decreased in obese subjects, and that this receptor modulates inflammatory gene expression in human adipocytes. The upregulation of α7nAChR by genistein stimulation opens new insights for the management of low-grade inflammation linked to human obesity.

Midline mandibular osteotomy in an asymmetric patient.

This case report shows the possibility of the application of a mandibular osteotomy to resolve mandibular asymmetry with independent and discordant movements of both bony segments. The authors report the case of a 25-year-old woman referred for mandibular asymmetry, with a transverse excess of the right hemi mandible and vertical defect of the left one. The patient underwent a bilateral sagittal split osteotomy, midline osteotomy, and genioplasty, which corrected the mandibular asymmetry with contraction of the entire right hemi mandible. A slight left vertical increase was also obtained through the surgically created lateral open bite. In the follow-up assessment, the patient's face appeared symmetrical with normalization of the bizygomatic-bigonial relationships, and the facial shape corresponded to ideal anthropometric features. This technique resulted in resolution of mandibular asymmetry. In addition, mandibular osteotomy permits the esthetic management of the shape of the entire mandibular body in relation to the other third of the face.

PI3K/Akt and ERK1/2 signalling pathways are involved in endometrial cell migration induced by 17beta-estradiol and growth factors.

Cell motility and invasion are crucial events for endometrial cells, not only for the establishment of pathological states but also during the physiological tissue remodelling that occurs during the menstrual cycle and embryo implantation. We have characterized these phenomena in endometrial stromal cells evaluating cell migration-specific stimuli and the biochemical pathways involved. Ability of endometrial cells to migrate on collagen type IV substrate was evaluated by means of chemotaxis experiments. Modulation of this phenomenon by different growth factors and steroid hormones and their ability to activate extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/Akt signalling in this context were examined. Platelet-derived growth factor (PDGF)-BB, epidermal growth factor and fibroblast growth factor-2 as chemoattractant agents stimulated basal migration of endometrial stromal cells through the rapid activation of both ERK1/2 and PI3K/Akt signalling pathways. Experiments using wortmannin and PD98059, specific inhibitors of the PI3K/Akt and ERK1/2 activity, respectively, showed that the activation of both pathways is required for growth-factor-induced cell motility responses. Similarly, 17beta-estradiol (10(-6)-10(-8) M) could enhance both constitutive and PDGF-induced migration of the cells and their rapid treatment with the hormone significantly increased phosphorylation of ERK1/2 and Akt. Conversely, progesterone did not interfere with the basal migration but inhibits the PDGF-induced motility of this cell type. Rapid activation of intracellular signalling cascades ERK1/2 and PI3K/Akt by growth factors and estrogens is involved in the migration of normal endometrial stromal cells.

Predictors of postabsorptive ghrelin secretion after intake of different macronutrients.

CONTEXT: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance. OBJECTIVE: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion. DESIGN: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients. SUBJECTS: Ten obese subjects (age, 31.8 +/- 2.5 yr; body mass index, 43.4 +/- 0.8 kg/m(2)) and six lean subjects (age, 33.5 +/- 2.4 yr; body mass index, 21.8 +/- 1.4 kg/m(2)) participated in the study. MAIN OUTCOME MEASURES: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and Delta of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals. RESULTS: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = -0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Delta and HOMA-S% (r = 0.60; P < 0.05). REE (beta = -0.57; P = 0.02) and ghrelin ApEn (beta = -0.62; P = 0.01) were predictors of postmeal ghrelin AUC and Delta, respectively. CONCLUSIONS: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility.

Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system.

In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent anti-proliferative/immunomodulatory effects on various tissues. Consistently, the enzyme that catalyzes the synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (1alpha-OHase) and the vitamin D receptor have a widespread tissue distribution. Among site-specific functions, the hormone has been suggested to be involved in uterine physiology. However, molecular analysis of the vitamin D system in normal endometrium throughout the menstrual cycle as well as its regulation in the context of endometrial physiological and pathological events have received very limited attention. Thus, we have studied expression, localization and regulation of 1alpha-OHase in human cycling and early pregnant endometrium. The capacity for 1alpha-hydroxylation and the presence of vitamin D receptor in endometrial cells have also been evaluated. The functional significance of these findings has been tested by evaluating gene expression of the catabolic enzyme, vitamin D 24-hydroxylase, and of the adhesion protein, osteopontin. Finally, to verify any potential dysfunction of the vitamin D system in endometriosis, a reproductive disease characterized by immune-mediated anomalies, we have analyzed expression of 1alpha-OHase in both eutopic and ectopic endometrium of affected patients. Results obtained showed that the active form of the 1alpha-OHase gene was expressed in human endometrial stromal cells independent of the cycle phase but with a significant increase in early pregnant decidua. A similar profile was observed for the protein, which was abundantly expressed in the cytoplasm of both endometrial stroma and epithelial glands. Both cycling and early pregnant endometrial cells also expressed the vitamin D receptor. In the same cells, 1alpha-OHase mRNA levels were significantly stimulated by the pro-inflammatory cytokine interleukin (IL)-1beta (50 and 500 pg/ml) while addition of the active form of the hormone could modulate both CYP24 and osteopontin gene expression. The 1alpha-OHase gene was also expressed in ectopic endometrium and its levels were increased in proliferative phase cultures derived from patients with endometriosis. Human cycling endometrium may be included among the extrarenal sites able to synthesize vitamin D. The IL-1beta-mediated induction of 1alpha-OHase gene and the hormonal modulation of osteopontin support a role for the hormone in the immunological mechanisms underlying uterine function. Abnormalities of this system are present in endometriosis.

Analysis of the codon 72 polymorphism of the TP53 gene in patients with endometriosis.

Endometriosis is a benign gynaecologic disease that is associated with a certain risk for malignant degeneration. The disease has a genetic background, but the locations of possible genomic aberrations are still poorly clarified. In this context, the proline form of TP53 codon 72 polymorphism has been recently associated with the risk of developing endometriosis. In this case-control study, we aimed to investigate further the potential association between endometriosis and this polymorphism in order to evaluate whether this genetic variant may influence the susceptibility to the disease. Genomic DNA was obtained from a consecutive series of 303 Italian Caucasian women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. Endometriosis was defined according to the criteria of Holt and Weiss [Holt V and Weiss NS (2000) Recommendations for the design of epidemiologic studies of endometriosis. Epidemiol 11,654-659] for the definite disease. Subjects of similar age without laparoscopic evidence of the disease served as control group. Molecular analysis of TP53 codon 72 polymorphism was performed by PCR amplification. Endometriosis was documented in 151 women. We found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes between patients with and without endometriosis. The respective proportions of arginine homozygotes, heterozygotes and proline homozygotes were 55.6, 39.7 and 4.6% in the group with endometriosis and 59.9, 30.9 and 9.2% in the control group. Moreover, no statistically significant association was demonstrated between TP53 codon 72 polymorphism and the various clinical manifestations of the disease, although a non-significant tendency towards an increased frequency of the proline allele was observed in association with specific manifestations of the disease reflecting a more severe form. Our results suggest that the TP53 codon 72 polymorphism does not confer genetic susceptibility to endometriosis in the Italian population. However, a possible susceptibility role of this polymorphism in endometriosis development towards very severe forms cannot be ruled out.

Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions.

BACKGROUND: Recent studies have proposed the measurement of CA 19-9 and IL-6 as an alternative to CA 125 as markers for endometriosis. This study was performed in order to verify the clinical value of serum CA 125, CA 19-9 and IL-6 levels, either by themselves or combined, in the detection of the disease. METHODS: In a prospective cohort study, serum concentrations of CA 125, CA 19-9 and IL-6 were measured in a consecutive series of 80 women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. RESULTS: Endometriosis was documented in 45 women (stage I-II in 14 cases and stage III-IV in 31 cases). Patients with endometriosis had significantly higher levels of CA 125 than controls [23.4 IU/ml (13.3-37.6) versus 11.4 IU/ml (9.1-18.5), P < 0.001)]. Conversely, women with and without the disease were shown to have similar levels of both IL-6 pg/ml [0.6 (undetectable-1.4) versus 1.0 pg/ml (0.4-1.9), P = 0.09] and CA 19-9 [9.8 IU/ml (4.5-20.8) versus 7.4 IU/ml (2.8-11.5), P = 0.11]. The area under the receiver operating characteristics curve resulted in a statistically significant difference from the null hypothesis only for CA 125 (P < 0.001). Sensitivity and specificity of CA 125 were 27 and 97% respectively and were higher than those related to CA 19-9 and IL-6. Concomitant use of the three dosages led to a sensitivity and a specificity of 42 and 71% respectively. CONCLUSIONS: The concomitant dosage of CA 125, CA 19-9 and IL-6 does not add significant information in respect to the CA 125 test alone in diagnosing either early or advanced stages of endometriosis.

Multicenter phase II study of CPT-11 fractionated over two days with bimonthly leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer.

PURPOSE: This multicenter phase II study evaluated the activity and toxicity of the combination of fractionated camptothecin (CPT-11) and 5-fluorouracil/leucovorin (5-FU/LV) (de Gramont regimen) for the treatment of metastatic colorectal cancer (MCC) patients who had received no prior chemotherapy for metastatic disease. PATIENTS AND METHODS: Fifty-four patients with a median age of 63.5 years (range: 43-75), received, every two weeks, a regimen consisting of 2 daily doses of CPT-11, 90 mg/m2 administered over a period of 90 minutes, followed by LV, 200 mg/m2 administered over 2 hours and 5-FU 400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour continuous infusion. Sixty-five percent of patients had synchronous metastatic disease at diagnosis, while 35% of the patients had received adjuvant chemotherapy after radical surgery. RESULTS: All 54 patients, receiving a total of 561 cycles of chemotherapy (median 12 per patient, range 1-26), were assessable for toxicity and response to treatment. The most common toxicities (grade 3-4) among treated patients were as follows: diarrhea in 3 patients, (6%), neutropenia in 9 patients (17%) and asthenia in 3 patients (6%), with no treatment-related death. We observed 4 complete (7.4%) and 18 partial responses (33.3%), giving an overall response rate of 40.7% (95% CI: 28% to 55%); 22 patients had stable disease (40.7%) and 10 patients progressed (18.5%). After a median follow-up of 22 months, the median time to progression was 8.7 months (range 2.3-43.9+), while overall median survival was 18.8 months (range 0.7-43.9+). CONCLUSION: The fractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed a lower gastrointestinal toxicity profile than expected, with substantial activity in patients with MCC.

Different basic fibroblast growth factor and fibroblast growth factor-antisense expression in eutopic endometrial stromal cells derived from women with and without endometriosis.

In all species studied, the basic fibroblast growth factor (bFGF) gene is transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS) probably involved in regulating the stability of the sense transcript. In this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women with endometriosis. bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 29 women without endometriosis and 24 patients affected by the disease. When the data were analyzed according to the phase of the menstrual cycle, endometrial stromal cells derived from patients in the late proliferative phase showed significantly higher bFGF mRNA values and significantly lower 1B FGF-AS mRNA levels compared with control samples. Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in endometrial stromal cells derived from patients compared with that in controls (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009). Moreover, for bFGF expression the differences existing at the mRNA level were maintained at the protein level. These findings support the hypothesis that 1B FGF-AS mRNA could regulate the expression of the sense transcript and suggest that in endometrial cells derived from patients, the presence of higher bFGF levels could improve their ability to proliferate at the ectopic site.

Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer, pre-treated with chemotherapy.

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.