Ultrasound morphometric and cytologic preoperative assessment of inguinal lymph-node status in women with vulvar cancer: MorphoNode study.

OBJECTIVE: To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer. METHODS: This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status. RESULTS: Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) length of the dominant LN (cut-off, 8.4 mm; sensitivity, 63.9%; specificity, 90.6%); C/medulla (M) thickness ratio of the dominant LN (cut-off, 1.2 mm; sensitivity, 70.4%; specificity, 91.5%), the combination of S length and C/M thickness ratio (sensitivity, 88.9%; specificity, 82.4%); and the FOA analysis (sensitivity, 85.9%; specificity, 84.2%). CONCLUSIONS: Preoperative ultrasound assessment, with or without the addition of cytology, has a high accuracy in assessing inguinal LN status in patients with vulvar cancer. In particular, the combination of two ultrasound parameters (S length and C/M thickness ratio) provided the greatest accuracy in discriminating between negative and positive LNs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Impact of bevacizumab containing first line chemotherapy on recurrent disease in epithelial ovarian cancer: A case-control study.

OBJECTIVE: To evaluate the timing and pattern of relapse, and duration of response to second line chemotherapy in advanced ovarian cancer (AOC) patients treated with first line carboplatin-paclitaxel chemotherapy with or without bevacizumab. PATIENTS AND METHODS: This is a case-control study including 222 AOC patients. Seventy-four women treated with first line carboplatin-paclitaxel-bevacizumab chemotherapy (Cases) were matched based on laparoscopic predictive index value, and residual tumor at first surgery with 148 AOC patients treated with carboplatin-paclitaxel. Distribution of pattern of relapse, and response to second line chemotherapy was compared between the two groups. Time to Progression (TTP) for second line chemotherapy was also analyzed for study purpose. RESULTS: Median platinum-free interval (PFI) was 16months (range 2-65) in Cases, compared with 9months (1-83) in Controls (p-value=0.001). Twenty patients (51.3%) among Cases showed recurrence in multiple anatomic sites, compared with 31 (31.9%) in the Control group (p-value=0.035). Peritoneal recurrence occurred as diffuse in 30 Cases (96.8%), and 60 Controls (82.2%; p-value=0.046). Secondary cytoreductive surgery (SCS) was successfully completed in 53.5% of Controls compared to 10.0% of Cases (p-value=0.016). In women with fully platinum-sensitive relapse, response rate to second line chemotherapy was 85.2% in Controls, compared to 38.4% in Cases (p-value=0.002). Finally, Cases showed a shorter TTP, compared to Controls (5months vs 8months; p-value=0.041). CONCLUSIONS: Incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with wider presentation of relapse, lower rate of complete SCS, and shorter TTP to second line chemotherapy in women with platinum-sensitive disease.

Glycemic control and weight changes in patients with type 2 diabetes intensified to three insulin regimens after therapeutic failure to exenatide.

The aim of this multicentre and observational study was to evaluate in a real life setting glycated haemoglobin A1(c), (HbA1c) as well as body weight outcomes in patients with type 2 diabetes in whom insulin was initiated after unsatisfactory response to exenatide, combined with maximal dosages of metformin and a sulfonylurea. We included 81 patients. In 56 patients, data were available after 6-8 and in 42 after 9-12 month's follow-up. Age and duration of diabetes were 57 +/- 11 and 11 +/- 6 years, respectively. Body mass index (BMI) was 32.4 +/- 6.9 kg/m2. Insulin was initiated with a basal insulin injection (22%), premixed insulin injections (48%) or a basal prandial scheme (30%). In the 6-8 and 9-12 month's cohorts, HbA(1c) decreased from 9.3 +/- 1.4 to 8.2 +/- 1.2% and from 9.3 +/- 1.3 to 8 +/- 1.1%, respectively (p < 0.0001). However, only 9 and 12% of subjects reached a target HbA(1c) of less than 7.0%, respectively. About half of the patients had HbA(1c) levels equal or higher than 8.0%. Insulin doses were progressively increased during the follow-up period. Insulin treatment was associated with a significant body weight increase (5-7 kg) (p < 0.0001). In conclusion, a high proportion of patients remained above the HbA(1c) targets after 6-12 month's treatment, despite a progressive increase in insulin dosages. Insulin treatment was associated with a marked weight gain.

One-year metabolic outcomes in patients with type 2 diabetes treated with exenatide in routine practice.

AIM: The study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages. METHODS: A total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA(1c), weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n=90) and 12 (n=94) months of follow-up. RESULTS: Significant decreases in HbA(1c) of -1.3% and -1.6% were observed in the 9- and 12-month cohorts, respectively (P<0.001). The decrease in HbA(1c) was greater in patients with higher baseline levels (P<0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P<0.001), with greater weight loss in patients with higher baseline BMI (P=0.046) and in female subjects (P=0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA(1c) and weight loss (P=0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n=77) mainly due to drug inefficacy (53%, n=41) or adverse events (26%, n=20), or both (8%, n=6). CONCLUSION: Exenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA(1c) and long duration of diabetes.

Challenging near infrared spectroscopy discriminating ability for counterfeit pharmaceuticals detection.

This study was initiated by the laboratories and control department of the French Health Products Safety Agency (AFSSAPS) as part of the fight against the public health problem of rising counterfeit and imitation medicines. To test the discriminating ability of Near InfraRed Spectroscopy (NIRS), worse cases scenarios were first considered for the discrimination of various pharmaceutical final products containing the same Active Pharmaceutical Ingredient (API) with different excipients, such as generics of proprietary medicinal products (PMP). Two generic databases were explored: low active strength hard capsules of Fluoxetine and high strength tablets of Ciprofloxacin. Then 4 other cases involving suspicious samples, counterfeits and imitations products were treated. In all these cases, spectral differences between samples were studied, giving access to API or excipient contents information, and eventually allowing manufacturing site identification. A chemometric background is developed to explain the optimisation methodology, consisting in the choices of appropriate pretreatments, algorithms for data exploratory analyses (unsupervised Principal Component Analysis), and data classification (supervised cluster analysis, and Soft Independent Modelling of Class Analogy). Results demonstrate the high performance of NIRS, highlighting slight differences in formulations, such as 2.5% (w/w) in API strength, 1.0% (w/w) in excipient and even coating variations (<1%, w/w) with identical contents, approaching the theoretical limits of NIRS sensitivity. All the different generic formulations were correctly discriminated and foreign PMP, constituted of formulations slightly different from the calibration ones, were also all discriminated. This publication addresses the ability of NIRS to detect counterfeits and imitations and presents the NIRS as an ideal tool to master the global threat of counterfeit drugs.

Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study.

OBJECTIVES: To assess feasibility, complications and efficacy of secondary surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in a selected group of platinum-sensitive recurrent ovarian cancer patients. METHODS: Recurrent ovarian cancer patients with a platinum-free interval of at least 6 months were prospectively enrolled. After complete CRS they were submitted to intraperitoneal perfusion of oxaplatinum (460 mg/m(2)) heated to 41.5 degrees C for 30 min. Then they received systemic chemotherapy with taxotere 75 mg/m(2) and oxaliplatin 100 mg/m(2) for 6 cycles. Patients were followed up routinely until recurrence or death. RESULTS: Twenty-five recurrent ovarian cancer patients were valuable for the study. The median Platinum Free Interval (PFI) was 25 months (range 7-67). The majority of the patients (76%) had diffuse carcinosis. Nobody had ascites. An optimal residual disease was obtained in all patients. The median duration of CRS+HIPEC was 312 min (range 138-619). Median intensive care unit (ICU) stay was 2 days (1-6), median hospital stay was 13 days (7-30). Post-operative major complications were observed in 7 patients (28%). Post-operative mortality was 0%. With a median follow-up time of 18 months (range 3-38), 24 patients (96%) are alive, but seven women (28%) have relapsed. CONCLUSIONS: Adequate pre-operative selection can improve feasibility of CRS and HIPEC. Morbidity rate is comparable to aggressive cytoreduction without HIPEC. Although associated with some post-operative morbidity, long-term results are encouraging, waiting for larger series and longer follow-up data.

Simultaneous quantitation of tobramycin and colistin sulphate by HPLC with evaporative light scattering detection.

A rapid and simple method for the simultaneous determination of tobramycin and colistin sulphate in a pharmaceutical formulation by reversed phase HPLC and evaporative light scattering detection is described. Chromatographic separation was carried out in gradient mode using a Zorbax SB C18 column (150mmx4mm, 3.5microm) with mobile phases of acetonitrile and water containing trifluoroacetic at 1ml/min. The method was validated using methodology described by the International Conference of Harmonization. The method was shown to be specific, precise, accurate and linear. Real samples were analyzed to demonstrate the applicability of the chromatographic method in a routine use.

Near InfraRed Spectroscopy homogeneity evaluation of complex powder blends in a small-scale pharmaceutical preformulation process, a real-life application.

Near InfraRed Spectroscopy (NIRS) is a potentially powerful tool for assessing the homogeneity of industrial powder blends. In the particular context of hospital manufacturing, we considered the introduction of the technique at a small pharmaceutical process scale, with the objective of following blend homogeneity in mixtures of seven components. This article investigates the performance of various NIRS-based methodologies to assess powder blending. The formulation studied is prescribed in haematology unit, as part of the treatment for digestive decontamination in children receiving stem-cell transplantation. It is composed of the active pharmaceutical ingredients (APIs) colimycin and tobramycin and five excipients. We evaluated 39 different blends composing 14 different formulations, with uncorrelated proportions of constituents between these 14 formulations. The reference methods used to establish the NIRS models were gravimetry and a High Performance Liquid Chromatography method coupled to an Evaporative Light Scattering Detection. Unsupervised and supervised qualitative and quantitative chemometric methods were performed to assess powder blend homogeneity using a bench top instrument equipped with an optical fibre. For qualitative evaluations, unsupervised Moving Block Standard Deviation, autocorrelation functions and Partial Least Square Discriminant Analysis (PLS-DA) were used. For quantitative evaluations, Partial Least Square Cross-Validated models were chosen. Results are expressed as API, and major excipient percentages of theoretical values as a function of blending time. The 14 different formulations were only satisfactorily discriminated by supervised algorithms, such as an optimised PLS-DA model. The homogeneity state was demonstrated after 16 min of blending, quantifying three components with a precision between 1.2% and 1.4% w/w. This study demonstrates, for the first time, the effective implementation of NIRS for blend homogeneity evaluation, as early as the preformulation step in a small hospital manufacturing unit. It shows how NIRS involving sampling with an optic fibre can be useful to characterise, optimise and control a small-scale mixing processes on the basis of the distribution of APIs and excipients during blending.

Protective effect of PEG 35,000 Da on renal cells: paradoxical activation of JNK signaling pathway during cold storage.

Polyethylene glycol (PEG), a high-molecular weight colloid, is added to preservation solutions in order to decrease cold- and ischemia-induced injuries of the grafted organ. We evaluated on LLC-PK1, a porcine proximal tubular epithelial cell line (1) the efficiency of several commercial preservation solutions (University of Wisconsin, Euro-Collins, Celsior, SCOT, IGL-1), and (2) whether adding PEG (400-35,000 Da) in a simple extracellular-type buffer modified cell integrity and mitogen-activated protein kinase (MAPK) signaling pathways. SCOT was the most efficient commercial solution. Moreover, only PEG 35,000 Da totally preserved cell viability, induced a decrease on reactive oxygen species production and a decrease on p38-MAPK activation. Furthermore PEG 35,000 Da stimulated c-Jun N-terminal kinase (JNK). However, the inhibition of JNK pathway, with the specific SP600125 inhibitor, in the presence of PEG 35,000 Da did not affect cell survival. We also confirmed on whole pig kidney the protective effect of PEG 35,000 Da on cold-induced tubular injuries. This study confirms PEG antioxidative properties, but we demonstrate that its effect on JNK signaling pathway had also a paradoxical effect on cell death. This sheds a new light on PEG effects during cell preservation, independently from the classical immuno-camouflaging hypothesis.

Near infrared spectroscopy and process analytical technology to master the process of busulfan paediatric capsules in a university hospital.

The prescription of unlicensed oral medicines in paediatrics leads the hospital pharmacists to compound hard capsules, such as busulfan, an alkylating agent prescribed in preparative regimens for bone marrow transplantation. In this study, we have investigated how the general principle of process analytical technology (PAT) can be implemented at the small size of our hospital pharmacy manufacturing unit. Near infrared spectroscopy (NIRS) was calibrated for raw material identification, blend uniformity analysis and final content uniformity of busulfan hard capsules of 11 different strengths. Measurements were performed on capsules from 2 to 40 mg (n=440). After optimisation, accuracy and linearity of the NIRS quantitative method was demonstrated after comparison with a previously validated quantitative high performance thin layer chromatography (HPTLC) method. Such a comparison led to attractive NIRS precision: +/-0.7 to +/-1.0 mg for capsules from 2 to 40 mg, respectively. As NIRS is a rapid and non-destructive technique, the individual control of a whole batch of busulfan paediatric capsules intended to be administrated is possible. Actually, mastering the process of busulfan paediatric capsules with the NIRS integrated into the notion of PAT is a powerful analytical tool to assess the process quality and to perform content uniformity of at least 5mg busulfan-containing capsules.

High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis.

BACKGROUND: Emerging evidence suggests a potential role for ubiquitous environmental contaminants in the physiopathology of endometriosis. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride (PVC) formulations, is a widespread environmental contaminant with potentially adverse effects on fertility in animal models. In the present study, we tested the hypothesis that DEHP and/or and its main metabolite, mono-ethylhexyl phthalate (MEHP), play a role in the pathogenesis of endometriosis. METHODS: Specimens of blood and peritoneal fluid were collected in a group of women with endometriosis (n = 55), and in age-matched control women (n = 24). Concentrations of DEHP and MEHP were measured in plasma and peritoneal fluid by using high performance liquid chromatography (HPLC). Differences between groups were tested using the Fisher's exact test, Wilcoxon-test, and Kruskal-Wallis analysis of variance. RESULTS: Endometriotic women showed significantly higher plasma DEHP concentrations than controls (median 0.57 micro g/ml, interquartile range: 0.06-1.23; values range: 0-3.24 versus median 0.18 micro g/ml, interquartile range: 0-0.44; values range: 0-1.03; P = 0.0047) and 92.6% of them had detectable DEHP and /or MEHP in the peritoneal fluid. No significant differences in either the DEHP/MEHP plasma concentrations (P >/= 0.31) or DEHP/MEHP peritoneal fluid concentrations (P >/= 0.66) were observed in the endometriotic patients as a function of the disease stage at the time of diagnosis. CONCLUSIONS: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.

Exposure to Di(2-ethylhexyl)phthalate in humans during pregnancy. A preliminary report.

BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer, is a widespread ubiquitous environmental contaminant. The potential health hazards from exposure to DEHP and its main metabolite, mono(2-ethylhexyl)phthalate (MEHP), have been well documented. Exposure to DEHP and MEHP in humans at risk, such as pregnant women and human fetuses, has not been tested. METHODS: Plasma DEHP and MEHP concentrations were measured in a total of 24 consecutive mother-infant pairs by high performance liquid chromatography. Associations between DEHP/MEHP and infant characteristics were tested using Fisher's exact test, unpaired t tests and univariate linear regression analysis. RESULTS: Measurable DEHP and MEHP concentrations were found in 17/24 (70.8%) and 18/24 (75%) maternal plasmas, respectively, and in 11/25 (44%) and 18/25 (72.0%) cord samples, respectively. Either DEHP or MEHP were detectable in 21/24 (87.5%) maternal plasmas and 19/25 (76%) cord samples. The mean DEHP concentrations in maternal and cord plasmas were 1.15 +/- 0.81 and 2.05 +/- 1.47 microg/ml, respectively. The mean MEHP concentrations were 0.68 +/- 0.85 and 0.68 +/- 1.03 microg/ml, respectively. No significant correlations were found between maternal and cord blood DEHP, maternal and cord blood MEHP, maternal DEHP and cord blood MEHP, or maternal MEHP and cord blood DEHP plasma concentrations. CONCLUSION: Although the effects of perinatal exposure to phthalates need further research, our findings: (i) confirm the high frequency of DEHP and/or MEHP exposure in human pregnancies; (ii) indicate that the exposure to these environmental contaminants begins during intrauterine life, and (iii) suggest that fetal exposure is closely related to the maternal exposure.

Hypersensitivity reaction to carboplatin: successful resolution by replacement with cisplatin.

Hypersensitivity reactions caused by carboplatin rarely occur. These reactions can cause lethal complications and make subsequent therapeutic approaches difficult. To date, only a few cases of successful resolution of hypersensitivity by replacement of carboplatin with cisplatin have been reported. We report on a patient with serous papillary extra-ovarian peritoneal carcinoma who developed a hypersensitivity reaction after the 10th weekly administration of carboplatin. Two weeks after reaction, intradermal skin testing with paclitaxel, carboplatin, cisplatin, and mannitol showed intense reaction only to carboplatin. On the basis of these results, the patient was changed to a chemotherapy with cisplatin and paclitaxel. A further eight courses of chemotherapy were administered without evidence of hypersensitivity reactions. Carboplatin seems to be successfully replaceable by cisplatin in case of hypersensitivity reactions.

Neurotoxicity of some MAO inhibitors in adult rat hypothalamic cell culture.

Monoamine oxidase-A (MAO-A) [amiflamine (AMF) and 4-methylthioamphetamine (MTA)] and MAO-B (L-deprenyl) inhibitors were found to be cytotoxic in a concentration-dependent manner for RCHT cells derived from adult rat hypothalamus. The cytotoxic effects were increased when the inhibitors were co-incubated with dicoumarol and especially with 25 micro M AMF+100 micro M dicoumarol (2.5-fold; P <0.001). The treatment of RCHT cells solely with AMF induced a marked decrease in the expression of DT-diaphorase mRNA.

Short-term weekly neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer.

Twenty patients with locally advanced cervical cancer (FIGO stage Ib-IIa "bulky"/IIb) were treated with three courses of weekly PVB (day 1: cisplatin, 50 mg/m2; vincristin, 1 mg/m2; bleomycin, 30 IU over 24-hr) in a neoadjuvant setting. Toxicity was generally mild (no grade 3-4 toxicity was observed), and the treatment was well tolerated without reduction of programmed dose intensity. Fourteen patients (70%) experienced a clinical response and underwent surgery within 20 days after the third course of chemotherapy. Six patients (30%) with stable disease were treated with salvage radiotherapy. Two of the 14 responders experienced a pathologic complete response (14.2%); microscopic disease was detected in one patient with clinical complete response. Pelvic node metastases were found in 4/14 patients (28.5%) and microscopic parametrium involvement in 3/14 (21.4%). All 14 patients had free margins of resection. A short-term weekly platinum-based chemotherapy is highly effective, has little toxicity, and allows a prompt salvage therapy for nonresponding patients.

Possible role of salsolinol quinone methide in the decrease of RCSN-3 cell survival.

The endogenous dopamine-derived neurotoxin salsolinol was found to decrease survival in the dopaminergic neuronal cell line RCSN-3, derived from adult rat substantia nigra in a concentration-dependent manner (208 microM salsolinol induced a 50% survival decrease). Incubation of RCSN-3 cells with 100 micro;M dicoumarol and salsolinol significantly decreased cell survival by 2.5-fold (P < 0.001), contrasting with a negligible effect on RCHT cells, which exhibited nearly a 5-fold lower nomifensine-insensitive dopamine uptake. The levels of catalase and glutathione peroxidase mRNA were decreased when RCSN-3 cells were treated with 100 microM salsolinol alone or in the presence of 100 microM dicoumarol. In vitro oxidation of salsolinol to o-quinone catalyzed by lactoperoxidase gave the quinone methide and 1,2-dihydro-1-methyl-6,7-isoquinoline diol as final products of salsolinol oxidation as determined by NMR analysis. Evidence of the formation of salsolinol o-semiquinone radical has been provided by ESR studies during one-electron oxidation of salsolinol catalyzed by lactoperoxidase.

Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line.

The mechanism of copper (Cu) neurotoxicity was studied in the RCSN-3 neuronal dopaminergic cell line, derived from substantia nigra of an adult rat. The formation of a Cu-dopamine complex was accompanied by oxidation of dopamine to aminochrome. We found that the Cu-dopamine complex mediates the uptake of (64)CuSO(4) into the Raúl Caviedes substantia nigra-clone 3 (RCSN3) cells, and it is inhibited by the addition of excess dopamine (2 m M) (63%, p < 0.001) and nomifensine (2 microM) (77%, p < 0.001). Copper sulfate (1 m M) alone was not toxic to RCSN-3 cells, but was when combined with dopamine or with dicoumarol (95% toxicity; p < 0.001) which inhibits DPNH and TPNH (DT)-diaphorase. Electron spin resonance (ESR) spectrum of the 5,5-dimethylpyrroline-N-oxide (DMPO) spin trap adducts showed the presence of a C-centered radical when incubating cells with dopamine, CuSO(4) and dicoumarol. A decrease in the expression of CuZn-superoxide dismutase and glutathione peroxidase mRNA was observed when RCSN-3 cells were treated with CuSO(4), dopamine, or CuSO(4) and dopamine. However, the mRNA expression of glutathione peroxidase remained at control levels when the cells were treated with CuSO(4), dopamine and dicoumarol. The regulation of catalase was different since all the treatments with CuSO(4) increased the expression of catalase mRNA. Our results suggest that copper neurotoxicity is dependent on: (i) the formation of Cu-dopamine complexes with concomitant dopamine oxidation to aminochrome; (ii) dopamine-dependent Cu uptake; and (iii) one-electron reduction of aminochrome.

Angiotensin receptor II is present in dopaminergic cell line of rat substantia nigra and it is down regulated by aminochrome.

Angiotensin receptor II mRNA was found to be expressed in dopaminergic neuronal cell line RCSN3 of rat substantia nigra using RT-PCR reaction. Aminochrome (150 microM), a metabolite of the dopamine oxidative pathway, was found to down regulate the expression of angiotensin receptor mRNA in RCSN3 cells by 83% (p < 0.05).

Cervical sarcoma botryoides treated with conservative surgery and adjuvant chemotherapy: a case report.

A case of cervical sarcoma botryoides treated with conservative surgery and adjuvant monochemotherapy is presented.