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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 109 records · Page 6Linked to original sources

Multimodal approach in invasive fetal therapy.

BACKGROUND: Integrated fetal therapy is a new approach to prenatal management consisting of a combination of invasive procedures which complement each other to provide as much information as possible on the fetal compartments. METHODS: We carried out a study on 50 fetuses of singleton pregnancies undergoing invasive procedures -- at least three per fetus -- for diagnostic and therapeutical purposes. A total of two hundred and fifty invasive procedures were adopted. The study population was divided into two groups, those studied between 1988 and 1992 and those studied between 1993 and 1995. RESULTS: The diagnostic and therapeutic utility of complementary invasive procedures in fetuses with nonimmune fetal hydrops and urinary tract malformations was assessed. In fetuses with nonimmune fetal hydrops integrated invasive procedures markedly affected the fetal-neonatal survival rate, whereas in those with urinary tract malformations scheduled for postnatal surgery these procedures made it possible to limit intrauterine renal damage. CONCLUSIONS: Complementary invasive procedures in NIFH fetuses particularly influence the fetal-neonatal survival rate. Since urinary tract malformations must be treated by postnatal surgery, complementary invasive procedures serve to limit intrauterine renal damage in the meantime and to reduce cesarean section rate.

Female↗

[A zinc sulfate and usnic acid preparation used as post-surgical adjuvant therapy in genital lesions by Human Papillomavirus].

BACKGROUND: To evaluate the efficacy and safety of intravaginal administration of a zinc sulphate and usnic acid compound as adjuvant therapy of Human Papillomavirus (HPV) genital infection, after radiosurgical treatment (RS). METHODS: One hundred patients affected by HPV genital infection were enrolled in the study from October 1996 to July 1998. Patients were classified according to colposcopic and cytologic criteria and treated with RS. Patients were randomized into three groups: the first group did not follow any therapy after RS (control group), (n = 50); the second group was pharmacologically treated with intravaginal administration of a usnic acid and zinc sulphate compound (Zeta N, Bergamon Italia) before and after RS (n = 25), the third group was pharmacologically treated only after RS (n = 25). The last two groups were considered together for the statistical analysis. Patients were reevaluated after one, two, three and six months from electrocoagulation. The safety of treatment was also investigated. RESULTS: One month after RS. HPV lesions disappeared in 93% of the patients in the control group and in 100% of patients treated with usnic acid and zinc sulphate. After one month, reepithelization was complete in 65% of cases treated with usnic acid and zinc sulphate and in only 28% of the control group (p = 0.001). Two months later reepithelization was 94% in the patients pharmacologically treated compared to 76% of the control group (p = 0.06). Treatment prior to RS resulted in a reduction of the overall area of lesions in 88% of cases. Three months after RS, there was a significant reduction of recurrence in the group treated with usnic acid and zinc sulphate (p = 0.01). This reduction was still significant at six months (p = 0.005). CONCLUSIONS: Usnic acid and zinc sulphate adjuvant treatment improved time of reepithelization and reduce the recurrence with few side effects and a good compliance.

Adult↗

Biological evaluation on different human cancer cell lines of novel colchicine analogs.

Three new 7-0-substituted deacetamidothiocolchicine derivatives have been evaluated for their antitumor activity against various human tumor cell lines, some of which express the multidrug resistance (MDR) phenotype, for their impact on the cell cycle and their binding to tubulin. Colchicine and thiocolchicine were used as reference compounds. Thiocolchicine was the most active agent on MDR-negative cells in terms of growth inhibition, whereas for multidrug-resistant cells, thiocolchicone was the most active compound (IC50 = 14 nM). As indicated by statistical analysis, a perfect agreement for the potency order (IC50 values) of the compounds between all the MDR-negative cancer cells (k = 1.00), a poor agreement between MDR-positive and MDR-negative cancer lines, and a moderate agreement (k = 0.50) between the two resistant cancer cells MCF-7 ADRr and CEM VBL were observed. To gain further insight into the mechanism of the antitumor activity of colchicinoids, the most active compounds, colchicone and thiocolchicone, were selected to evaluate their effect on cell cycle, apoptosis, and tubulin interaction. The highest recruitment activity into the G21/M phase of the cell cycle was detected in thiocolchicone-treated breast cancer cells. Interestingly, after 72 h of culture, when the cell cycle block subsided, a consistent amount of DNA fragmentation, a hallmark of apoptosis, was evident. Morphological analysis of MCF-7 ADRr cells confirmed this hypothesis and revealed that thiocolchicone was able to induce apoptosis in this MDR-bearing model. We also demonstrated, using flow cytometry, that thiocolchicone interacts with alpha- and beta-tubulin, thereby affecting the expression of both subunits.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The antioxidants (coenzyme Q10) in materno-fetal physiopathology].

BACKGROUND: Coenzyme Q10 (ubidecarenone) is a torpeniod molecule mainly located in bacterial and mitochondrial membranes. It is a part of a specific enzyme system and acts primarily on the transport of electrons in the mitochondrial respiratory chain. It performs an antioxidant action. We studied both fetal and maternal coenzyme Q10 plasma levels in physiological conditions and also in the presence of some pathologies. METHODS: As regards the maternal side, we selected 483 pregnancies, performing 615 blood samples, and divided them into four groups: A: physiological pregnancies; B: spontaneous abortions; C: threatened abortions; D: threatened late abortions and threatened pre-term deliveries. We then selected 61 pregnancies which differed from the previous ones and determined Q10 levels in fetal samples obtained by cordocentesis. We divided a control group from pathological groups: intra-uterine growth retardation (IUGR); Rh-isoimmunization (with intra-uterine transfusion), non immune fetal hydrops, fetal malformations. Coenzyme Q10 levels were determined in only one laboratory by high-performance liquid chromatography (HPLC). Coenzyme Q10 concentrations were expressed as mg/ml, the data as the mean + SD. Statistical analysis was performed employing a linear regression model and the student "t"-test. RESULTS: After working out a normality curve of CoQ10 levels in maternal blood, we noticed that the levels of Coenzyme Q10 were low in spontaneous abortions, in threatened late abortions and in threatened pre-term deliveries. We determined the value of 0.3 mg/ml as a cutoff to differentiate the fetal from the adult values. Moreover, CoQ10 values turned out to be increased only in fetuses affected by non-immune fetal hydrops. CONCLUSIONS: Accordingly, we can say that maternal CoQ10 plasma levels can be considered as a marker of pathological uterine contractile activity. There is a substantial increase in CoQ10 fetal plasma levels in fetuses affected by hypoxic hypoxia and also in those affected by non-immune fetal hydrops.

Abortion, Spontaneous↗

Cytotoxic effects toward human hematopoietic progenitor cells and tumor cell lines of paclitaxel, docetaxel, and newly developed analogues IDN5109, IDN5111, and IDN5127.

The growth inhibitory effect of paclitaxel, docetaxel, and newly developed taxanes IDN5109, IDN5111, and IDN5127 was assessed on peripheral blood (PB) CD34+ maintained in liquid culture and on three human cancer cell lines (MDA-MB231, MCF-7 ADRr, CEM VBLr). Concomitantly, DNA analysis was also performed. For unfractionated peripheral blood progenitor cells (PBPC) toxicity was also assessed by clonogenic assay. The cytotoxic effects induced by taxanes toward PBPC as measured by clonogenic assay were correlated with those found for multidrug resistance (MDR)-positive cell lines (IDN5109 > IDN5111 > IDN5127 > docetaxel > paclitaxel). We established a therapeutic index (TI) between the antitumor activity in MDR-positive cells and the toxicity toward PBPC. Paclitaxel and IDN5109, as determined by TI, showed the best value in MDR-negative and MDR-positive cells, respectively. The ranking of the cytotoxic effects observed in PB CD34+ was not correlated with that obtained in clonogenic assay and in cancer cells (IDN5127 > IDN5109 > docetaxel > IDN5111). Remarkably, in DNA analysis docetaxel induced the maximal cell cycle blocking activity. Newly developed taxanes IDN5109 and IDN5111 are endowed of a profile of anticancer activity in MDR-bearing cells and toxicity toward hematopoietic progenitors better than that of docetaxel. However, mechanism(s) underlying toxicity toward hematopoietic progenitors could be, at least in part, different from that of docetaxel and likely dependent on the interaction with P-glycoprotein function in PB CD34+ cells.

Antigens, CD34↗

Comparative study on the induction of cytostasis and apoptosis by ICI 182,780 and tamoxifen in an estrogen receptor-negative ovarian cancer cell line.

We have compared the effects of a broad range of clinically relevant concentrations (0.1 to 10 microM) of the steroidal pure anti-estrogen ICI 182,780 and the non-steroidal partial anti-estrogen tamoxifen (TAM) on cell proliferation and induction of apoptosis in the estrogen receptor (ER)-negative ovarian carcinoma cell line A2780. Cell proliferation was assessed by evaluating the number of viable cells, changes in cell-cycle distribution and cell replication rate; while apoptosis induction was assessed by examining nuclear morphological changes associated with apoptotic death and DNA cleavage into 300 and 50 kbp units (large DNA fragmentation) and into 180 bp units (internucleosomal DNA fragmentation). We provide evidence that 0.1 to 10 microM ICI 182,780 and TAM significantly inhibit the growth of A2780 cells in a dose-dependent fashion. Cytokinetic analysis revealed that only 10 microM TAM caused a significant blockade in G1 and a diminished replication rate. Conversely, we show that 0.1 to 10 microM ICI 182,780 and TAM induce apoptosis in a dose-dependent fashion. The earliest recognizable apoptotic change induced by treating the cells with these 2 drugs was DNA cleavage into 300 and 50 kbp units. This started to be visible in adherent cells, implying that apoptosis induction by ICI 182,780 and TAM was not determined by the loss of cell-substrate interaction. A further degradation of 300 and 50 kbp DNA fragments occurred in cells that had lost their adhesion to the culture plate. We observed the ladder pattern typical of internucleosomal DNA cleavage by treating A2780 cells with the highest dose (10 microM) of ICI 182,780 and TAM. Lower concentrations of these 2 drugs (0.1 to 1 microM) did not produce such a pattern of DNA fragmentation. Typical features of apoptotic nuclei were detectable after both drug treatments. However, cells undergoing apoptosis induced by ICI 182,780 showed hyper-aggregation of chromatin, whereas TAM-treated cells preferentially exhibited chromatin clumping.

Antineoplastic Agents↗

Epidermal growth factor receptor (EGFR) is not related to the prognosis of cervical cancer.

We analyzed the prognostic significance of epidermal growth factor receptor (EGFR) in a large prospective series of 90 cervical cancer patients observed for a long follow-up period. EGFR levels ranged from 0 to 52.1 fmol/mg protein, with a median value of 6.0 fmol/mg protein. Patients with an advanced stage of disease expressed lower EGFR levels than those with an early stage of disease (median values were 7.8 fmol/mg protein for patients with stage I-II and 4.2 fmol/mg protein for patients with stage III-IV, P = 0.013). There was no correlation between EGFR expression and other clinicopathological parameters analyzed. No significant relationship was shown between EGFR positivity and overall survival. No significant relationship between EGFR status and disease-free survival was observed. Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels are not associated with the risk of disease recurrence after treatment or death (P-value not significant). Our data didn't seem to indicate a prognostic role of EGFR in cervical cancer.

Adult↗

Analysis of cyclin E and CDK2 in ovarian cancer: gene amplification and RNA overexpression.

Cyclins and their associated kinases (cdks) play a key role in controlling the cell cycle, a process whose disregulation can potentially lead to uncontrolled cell growth and hence to cancer. We have studied the role of both cyclin E and its associated kinase cdk2 in ovarian cancer. Primary, metastatic, recurrent and benign ovarian tumors were screened for cyclin E and cdk2 gene amplification. Cyclin E was shown to be amplified in 21% and cdk2 in 6.4% of the cases analyzed. Cyclin E and cdk2 RNA expression levels were determined by semi-quantitative RT-PCR analysis in a partially overlapping series of samples and compared to the expression levels of normal ovarian surface epithelial cells. Cyclin E RNA was overexpressed in 29.5% and cdk2 in 6.5% of ovarian tumors tested. We determined that in most cases gene amplification leads to higher RNA levels for cyclin E and that the overall levels of cyclin E and cdk2 RNA were correlated. We hypothesize that cyclin E and cdk2 are, in part co-regulated and that they may concur to ovarian tumor development.

Adult↗

Role of opioid tone in the pathophysiology of hyperinsulinemia and insulin resistance in polycystic ovarian disease.

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by naltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.

Adolescent↗

Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer.

The aim of this study was to analyse the long-term survival and the relationships between prognostic factors at presentation, chemoresponsiveness and disease outcome in patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery (RS). Two consecutive studies of neoadjuvant chemotherapy containing cisplatin, bleomycin plus/minus methotrexate followed by radical hysterectomy and systematic aortic and pelvic lymphadenectomy were carried out between January 1986 and September 1990 on 130 patients with > or = 4 cm stage IB2-III cervical cancer. Survival analysis was performed using the Kaplan and Meier test and Cox's multivariate regression analysis. 128 (98%) of the patients enrolled were evaluable for clinical response and survival, 83% (106) of the patients responded to chemotherapy, with a 15% complete response rate. Logistic regression analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) stage, cervical tumour size, parametrial involvement and histotype are highly predictive of response. Responding patients underwent laparotomy, but 8% were not amenable for radical surgery. The 10-year survival estimates were 91%, 80% and 34.5% for stage IB2-IIA bulky, IIB and III, respectively (P < 0.001). After Cox's regression analysis, the parameters significantly associated with survival were the same factors predicting response to neoadjuvant chemotherapy. No stage IB2-IIA bulky patient has so far relapsed, while 12% stage IIB and 56% stage III patients recurred. The 10-year disease-free survival estimates are 91% and 44% for stage IB2-IIB and III, respectively (P < 0.001). Metastatic nodes and persistent tumour in the parametria were the only two independent factors for disease-free survival after multiple regression analysis. After a long-term follow-up (median follow-up 98 months (20-129+)), our results give new evidence of the prognostic value of response to neoadjuvant chemotherapy and of a possible therapeutic benefit of the sequential treatment adopted which, however, must be verified in a randomised setting.

Adult↗

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

Carboxylic Ester Hydrolases↗

In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Immunoradiometric and immunohistochemical analysis of Cathepsin D in ovarian cancer: lack of association with clinical outcome.

The aim of this study was to analyse the clinical significance of Cathepsin D (Cath D) content as determined by an immunoradiometric assay in a series of primary untreated ovarian cancers from 162 patients. In addition, immunohistochemical analysis of Cath D was also performed on a subset of 86 tumours. Cath D levels were distributed in an asymmetrical way and were skewed towards the lower values (median value 20.8 pmol mg(-1) protein, range 2.0-99.0 pmol mg(-1) protein). No correlation was found between Cath D levels and clinicopathological parameters. However, the percentage of Cath D positivity was significantly higher in oestrogen receptor-positive (57%) compared with oestrogen receptor-negative (36%) cases (P= 0.01). The percentage of Cath D-positive staining was not significantly different for both epithelial (27%) and stromal components (40%). Immunoradiometrically detected Cath D levels were not different according to Cath D stromal immunostaining (P= 0.18), while higher Cath D levels were measured in Cath D-positive than in Cath D-negative tumour epithelial cells (P = 0.027). Survival analysis was conducted on 161 primary untreated ovarian cancer patients. The 5-year overall survival rate was 57% and 55% in Cath D-positive and Cath D-negative patients respectively (P = 0.69). As far as time to progression was concerned, there was no significant difference in the survival rate of patients with either high or low Cath D content (P = 0.56). Similar results have been obtained in the subset of patients in which Cath D was analysed by immunohistochemistry. In conclusion, Cath D measurement in tumour extracts appears to have a limited usefulness in improving the prognostic characterization of ovarian cancer patients.

Cathepsin D↗

Functional, phenotypic and molecular characterization of cytokine low-responding circulating CD34+ haemopoietic progenitors.

Circulating CD34+ cell populations characterized by a low rate (up to five) or high rate (more than five) of cell divisions were isolated from 8 d cultures in the presence of stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), erythropoietin (EPO), Flt3 ligand and Peg-rHu megakaryocyte growth and development factor (Peg-rHuMGDF) using the fluorescent dye 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and flow cytometric cell sorting. Phenotypic characterization of cells which had experienced up to five divisions (CFDA-SEbright) showed a similar surface antigen expression to starting, freshly isolated CD34+ cells. Conversely, cells which experienced more than five divisions (CFDA-SEdim) showed a differentiating behaviour, down-regulating CD34 antigen and acquiring differentiation markers. CFDA-SEbright cells were significantly enriched in CD105 (endoglin) positive precursors as compared to both freshly isolated CD34+ and CFDA-SEdim cells. Functional analysis indicated that CFDA-SEbright had a 3-fold and 10-fold greater cumulative cloning efficiency as compared to freshly isolated CD34+ cells and CFDA-SEdim cells, respectively. CFDA-SEbright cells retained the vast majority of LTC-IC and showed a LTC-IC frequency 2.8-fold higher than that found in freshly isolated CD34+ cells. RT-PCR and Western blot analyses showed significantly higher bcl-2 RNA and protein levels in CFDA-SEbright cells as compared to freshly isolated CD34+ and CFDA-SEdim cells. This study indicates that cytokine low-responding circulating CD34+ cells (CFDA-SEbright cells) represent a functionally, phenotypically and molecularly distinct multipotent progenitor population with biological properties associated with primitive precursors.

Antigens, CD↗

Postoperative adhesion prevention with low-dose aspirin: effect through the selective inhibition of thromboxane production.

The aim of the present study was to evaluate the efficacy of low-dose versus high-dose aspirin in the prevention of postoperative adhesion formation. Forty New Zealand White rabbits were randomized into three groups: low-dose aspirin (1.7 mg/kg per day for 5 days starting on the day of surgery), high-dose aspirin (28.0 mg/kg per day), and controls. The rabbits underwent a standardized surgical injury on the ovary, uterine horn and abdominal wall on one side at laparotomy. On postoperative day 21, a second-look laparotomy was performed for the evaluation of postoperative adhesions. In five animals in each group, peritoneal fluid samples were collected at initial surgery, then through an additional 2 cm incision performed on postoperative day 3, and at second-look laparotomy. The peritoneal concentrations of thromboxane B2 and 6-keto-prostaglandin F1alpha (the stable hydrolysis product of prostacyclin) were measured by radioimmunoassay. At second-look laparotomy, the adhesion formation rate was 46% in the low-dose aspirin group, 77% in the high-dose group, and 100% in the control group. The adhesion score in the low-dose group was significantly lower (P < 0.01) than in the high-dose and control groups. Peritoneal thromboxane decreased significantly during treatment in both low-dose and high-dose aspirin groups, whereas prostacyclin decreased only in the high-dose group. Postoperative adhesion reduction observed in this study with low-dose aspirin treatment could be due to the selective inhibition of thromboxane over prostacyclin production.

Abdominal Muscles↗

Endothelin-1 inhibits basal and human chorionic gonadotrophin-stimulated progesterone production.

Endothelin-1 (ET-1) is a peptide classically produced by endothelial cells and known for its powerful vasoconstrictor activity. However, recent data suggest an involvement of ET-1 also in reproductive function. This study was designed to examine the possible presence and role of ET-1 in human luteal cells. Purified luteal cells were incubated for different times with ET-1 (10(-9)-10(-6) M) or ET-3 (10(-9)-10(-6)) alone or associated with human chorionic gonadotrophin (HCG) (100 ng/ml). Both basal and HCG-induced progesterone production were significantly reduced by ET-1 at all examined times whereas preincubation of luteal cells with BQ485 (10(-9)-10(-6) M), an ET-A receptor antagonist, prevented the inhibitory effect of ET-1. Conversely, no effect on progesterone synthesis was observed when ET-3 was added to the cultures. Luteal cells were then incubated for 24 h with phorbol 12-myristate-13 acetate (PMA) (100 ng/ml), an activator of protein kinase C. Inhibition of progesterone synthesis by PMA was similar to that induced by ET-1 alone. This study demonstrates that ET-1 negatively affects, at physiological concentrations, basal and HCG-induced progesterone synthesis. These effects seem to be exerted through the ET-A receptors and the protein kinase C pathway. Conversely, ET-3 was not able to influence human luteal steroidogenesis.

Cells, Cultured↗

Human immunodeficiency virus seroprevalence and condom use among female sex workers in Italy.

BACKGROUND AND OBJECTIVES: In two different studies, we evaluated the human immunodeficiency virus (HIV) seroprevalence rate and the condom use in a group of female sex workers working in Italy. STUDY DESIGN: In the first study we collected data on HIV serologic testing of female sex workers; in the second study, we evaluated the use of condoms and high-risk sexual practices by sex workers with their clients and nonpaying partners. RESULTS: Overall, 131 of 802 (16%) were HIV positive: 36 of 558 (6%) professional sex workers and 95 of 244 (39%) sex workers who used intravenous drugs. There was a significant increase of seroprevalence among professional sex workers between 1988 to 1990 and 1991 to 1995 (2% versus 11%, P < or = 0.001), whereas among the sex workers who used intravenous drugs, the increase was not significant (37% versus 40%, P = 0.70). Similarly, the HIV seroprevalence in the Italian professional sex workers is constant in the two periods of time (2% versus 1%). In the second study, 97 of 102 (95%) sex workers reported regular condom use with clients, whereas 63% of sex workers reported they never used them with nonpaying partners. Fourteen sex workers reported having nonpaying partners who used intravenous drugs and 6 reported having nonpaying bisexual partners; 8 of these 20 partners were HIV positive. CONCLUSION: The results of the first study showed a significant increase of seroprevalence among professional sex workers, whereas the high seroprevalence among sex workers who used intravenous drugs was constant. The results of the second study showed that sex workers may be at higher risk for HIV infection through noncommercial sexual intercourses.

Adult↗

Concurrent HPV infection in oral and genital mucosa.

Screening for human papillomavirus (HPV) types was performed by a PCR-based assay on 29 women (mean age 34.0 years, range 21-48 years). HPV-DNA was demonstrated in 16 women (55.2%), with a detection rate of 37.9% in the oral cavity and 34.5% in the genital tract. HPV-16 was the most prevalent genotype (53.8%), followed by HPV-6, which was present in 34.6% of the positive samples. Other types were more rarely detected. Five subjects showed concurrent genital tract and oral cavity infections but HPV type-specific concordance was detected in only 3 patients. Multiple HPV infections were found in 9 of the 26 positive samples, where HPV-6 appeared frequently associated with the other types. These data confirm the occurrence of mixed HPV infections and the wide diffusion of different types of HPV in the genital mucosa and in the oral cavity; they also stress the need to utilize diagnostic methods with a wide typing capacity.

Adult↗