Prognostic role of immunosuppressive acidic protein in advanced ovarian cancer

OBJECTIVE: Our purpose was to investigate immunosuppressive acidic protein in the prognostic characterization of advanced ovarian cancer. STUDY DESIGN: Serum levels of immunosuppressive protein were prospectively measured in 80 patients with untreated ovarian carcinoma. To evaluate the prognostic significance of immunosuppressive acidic protein levels, cutoff points were studied every 50 μg/ml between 450 and 1350 μg/ml. RESULTS: Pretreatment immunosuppressive acidic protein levels were not significantly associated with stage, histotype, grade of differentiation, postoperative residual tumor, and response to chemotherapy. The most significant association with survival was observed at a cutoff value of 1100 μg/ml (p = 0.0089). In the univariate analysis for overall survival, International Federation of Gynecology and Obstetrics stage and immunosuppressive acidic protein status were found to have a role in predicting ovarian cancer prognosis. In the multivariate analysis only immunosuppressive acidic protein status was significantly associated with survival. A statistical correlation was found between serum levels and overall survival (p = 0.0104, χ² 6.56), including immunosuppressive acidic protein as a continuous variable. CONCLUSION: Our data suggest that immunosuppressive acidic protein assay is a potentially useful tool in the prognostic characterization of advanced ovarian cancer. (Am J Obstet Gynecol 1996;175:1606-10.)     

The effect of 2 bleaching agents on the enamel surface. An in-vitro study]

We present a study "in vitro" of the effect of bleaching agents on dental surfaces using the "Walking bleaching technique". We found that hydrogen peroxide bleached more quickly than carbamide although, after a period of six weeks, the results were the same as far as whitening was concerned. In the scanning electron microscope we observed significantly different changes in each case. Carbamide caused a regular and uniform opening of the enamel prisms of the surface while hydrogen peroxide produced more severe superficial destruction with the appearance of patterning similar to the acid etching, and the presence of some crystalline areas emerging from the body of the prisms.     

Pyrosequencing for detection of mutations in the connexin 26 (GJB2) and mitochondrial 12S RNA (MTRNR1) genes associated with hereditary hearing loss

Hereditary hearing loss (HHL) is one of the most common congenital disorders and is highly heterogeneous. Mutations in the connexin 26 (CX26) gene (GJB2) account for about 20% of all cases of childhood deafness, and approach 50% in documented recessive cases of non-syndromic hearing loss. In addition, a single mitochondrial DNA mutation, mt1555A>G, in the 12S rRNA gene (MTRNR1), is associated with familial cases of progressive deafness. Effective screening of populations for HHL necessitates rapid assessment of several of these potential mutation sites. Pyrosequencing links a DNA synthesis protocol for determining sequence to an enzyme cascade that generates light whenever pyrophosphate is released during primer strand elongation. We assessed the ability of Pyrosequencing to detect common mutations causing HHL. Detection of the most common CX26 mutations in individuals of Caucasian (35delG), Ashkenazi (167delT), and Asian (235delC, V37I) descent was confirmed by Pyrosequencing. A total of 41 different mutations in the CX26 gene and the mitochondrial mt1555A>G mutation were confirmed. Genotyping of up to six different adjacent mutations was achieved, including simultaneous detection of 35delG and 167delT. Accurate and reproducible results were achieved taking advantage of assay flexibility and experimental conditions easily optimized for a high degree of standardization and cost-effectiveness. The standardized sample preparation steps, including target amplification by PCR and preparation of single-stranded template combined with automated sequence reaction and automated genotype scoring, positions this approach as a potentially high throughput platform for SNP/mutation genotyping in a clinical laboratory setting. .     

Multiple pathways of cell invasion are regulated by multiple families of serine proteases

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell. This revised version was published online in July 2006 with corrections to the Cover Date.     

Identification, characterization and biological activity of oxytocin receptor in the developing human penis

Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log(10) unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

Transthoracic 2D echo color Doppler assessment of internal mammary artery to left anterior descending coronary artery graft

For noninvasive evaluation of anatomy and flow characteristics of internal mammary artery graft (IMA-graft), 2D echo-Color-Doppler (CDE) was performed in 60 patients (54 M, 6 F, mean age 54.1±6.9 y), who underwent coronary angiography 20.1 ±13 months after a coronary artery bypass graft (CABG).CDE was performed, using an echocardiographic unit equipped with a 5 MHz linear transducer.In all patients, measurements of IMA-graft diameter (mm), and peak systolic and diastolic flow velocity (cm/sec) were obtained at baseline and also in 16 patients after dipyridamole infusion (0.54 mg/Kg/min) and in 10 patients after sublingual nitroglycerin (NTG) (0.4 mg). Angiography showed the IMA-graft patency in 58/60 patients (96.8%).A typical biphasic flow was displayed by CDE in 49/58 patients (84.4%) with angiographic patency.Dipyridamole infusion increased both IMA-graft diameter and peak diastolic flow velocity (PDFV) from 2.28 ±0.51mm to 2.9 ±0.42mm and from 19.4 ±6.2 cm/sec to 93.9 ±29 cm/sec, respectively (p<0.0001).No significant modifications of peak systolic flow velocity (PSFV) were observed.NTG increased PDFV from 29.11 ±8 cm/sec to 41.88 ±7.20 cm/sec (p<0.005), while diameter and PSFV showed no statistically significant modifications.CDE is a useful diagnostic tool for noninvasive evaluation of IMA-graft patency both early after surgery and during long-term follow-up. CDE pharmacological stress improves the sensibility of the technique and it can provide indirect information about pathophysiology of recipient coronary vessel.