Mid-IR band strength, density, refractive index, and thermal evolution study for solid CH2DOH pure and in astrophysical relevant mixtures.

We present a novel experimental study on solid CH2DOH pure and in astrophysical relevant mixtures. Solid samples were accreted under ultra high vacuum conditions at 17 K and were analyzed by mid-infrared transmission spectroscopy. Refractive index, density, and mid-IR band strength values were measured for pure solid CH2DOH. The refractive index was also measured for CH2DOH:H2O, CH2DOH:CO, and CH2DOH:CH3OH mixtures. For all samples, the thermal evolution of the main band profile was studied. We used the interference laser technique (HeNe laser, λ = 543.5 nm) to measure the samples thickness and a numerical method to measure the refractive index starting from the amplitude of the interference curve. We obtained the ice density through the Lorentz-Lorenz relation. To calculate the band strength values we used the linear fit of the integrated band intensities with respect to the column densities. Samples deposited at 17 K were warmed up to their sublimation temperature. Spectra were taken at selected temperatures to study their thermal evolution. The results are discussed in view of their relevance for the interpretation of astronomical IR spectra.

Presence of cancer cells in gastric lavage of gastric cancer patients as an indicator of advanced disease, predictor of tumour aggressive phenotype and independent prognostic factor for poor survival: The endoluminal metastatic pathway of gastric cancer and GL0/GL1 classification.

OBJECTIVE: As of 2017, the pathobiology of gastric cancer (GC) is far from fully understood; consequently, new methods of basic and advanced research have been proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with diagnostic intent but not for staging or prognostic assessment. We investigated this hitherto unreported application of cytopathology. METHODS: GL was preoperatively and prospectively collected from 80 GC patients and cytologically analysed. The results were compared with the classic clinicopathological features of GC and related to survival. The prognostic value of GL1 was assessed through univariate and multivariate analyses. RESULTS: GL1 was detected in 36 samples (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024, .003 and .0028, respectively). Overall survival (OS) was significantly shorter for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1 subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1, N+, M1, LVI1 and advanced stage were significantly associated with OS. Multivariate analysis assessed GL1 as the only independent prognostic factor for worse OS and progression-free survival (P=.0013 and .0107). CONCLUSIONS: In the present study, GL1 was correlated with advanced disease, aggressive tumour behaviour and poor prognosis. Although additional studies are needed to confirm these findings, the GL0/GL1 classification can be applied to GC patients to achieve higher accuracy in staging, prognostic stratification and treatment selection.

Renin-angiotensin system at the crossroad of hypertension and hypercholesterolemia.

AIM: The aim of this study is to discuss the reliable scientific evidence of an interactive link between hypertension and hypercholesterolemia considering the metabolic pathways and the pathogenetic mechanisms connecting the two risk factors. DATA SYNTHESIS: Hypertension and hypercholesterolemia are highly prevalent in the general population and their coexistence in the same subjects additively increases the risk of cardiovascular disease. Probably, hypercholesterolemia is also a risk factor for the development of hypertension. On the other side, it is also possible that lipid-lowering treatment could improve blood pressure control. Although the mechanisms of interaction between these two risk factors have not been completely elucidated thus far, there is rapidly growing evidence that the involvement of the renin-angiotensin system (RAS) can be considered as the common link between hypertension and hypercholesterolemia. In particular, hypercholesterolemia seems to promote the upregulation of type 1 angiotensin II (AT1) receptor genes because of an increase in the stability of mRNA followed by structural overexpression of vascular AT1 receptors for angiotensin II. The treatment of both risk factors greatly improves individual risk profile, especially when statins and RAS blockers are used together. CONCLUSIONS: Hypertension and hypercholesterolemia are highly coprevalent and strongly related from a pathophysiological point of view. The RAS could be the main mediator of this link.

[Is viscoelastic the corneal tissue?]. / Il tessuto corneale è viscoelastico?

PURPOSE: To compare the known viscoelastic properties of soft tissues with singular published observations on the behaviour of corneal tissue. MATERIALS AND METHODS: The behaviour of the maxwellian element, typical viscoelastic biomechanical model, is compared with that of various previously studied soft tissues of animals. The same comparison can be made between stress-strain curves of riboflavin and UVA treated and untreated strips of human and porcine corneal tissue, stretched at constant velocity, from the literature. RESULTS: The asymptotic stress-strain curves of the various soft tissues previously examined could be faithfully simulated by the Maxwell viscoelastic element. The exponential stress-strain curves of samples of corneal tissue were clearly different. CONCLUSIONS: The observed divergence demonstrates incompatibility between the alleged behaviour of corneal tissue and the viscoelastic properties attributed to it. Thus there are two possibilities: either corneal tissue is viscoelastic and the experiment showing exponential behaviour suffers from some technical problem, or the data is correct and corneal tissue is not viscoelastic. In either case further research is necessary for correct interpretation of the mechanism of cross-linking and for consequent therapeutic choices.

Prognostic significance of serum uric acid in outpatients with chronic heart failure is complex and related to body mass index: data from the IN-CHF Registry.

BACKGROUND AND AIMS: In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF). METHODS AND RESULTS: All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p < 0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹. CONCLUSION: Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.

Keratoconus, cross-link-induction, comparison between fitting exponential function and a fitting equation obtained by a mathematical model.

With reference to experimental data in the literature, we present a model consisting of two elastic elements, conceived to simulate resistance to stretching, at constant velocity of elongation, of corneal tissue affected by keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross-linking. The function describing model behaviour adapted to stress and strain values. It was found that the Young's moduli of the two elastic elements increased in cross-linked tissues and that cross-linking treatment therefore increased corneal rigidity. It is recognized that this observation is substantially in line with the conclusion reported in the literature, obtained using an exponential fitting function. It is observed, however, that the latter function implies a condition of non-zero stresses without strain, and does not provide interpretative insights for lack of any biomechanical basis. Above all, the function fits a singular trend, inexplicably claimed to be viscoelastic, with surprising perfection. In any case, using the reported data, the study demonstrates that a fitting equation obtained by a modelling approach not only shows the evident efficacy of the treatment, but also provides orientations for studying modifications induced in cross-linked fibres.

Prognostic value of differential expression of Laminin-5 gamma2 in oral squamous cell carcinomas: correlation with survival.

In oral squamous cell carcinomas of the head and neck, Laminin-5 gamma2 has been associated with tissue invasion, lymph node metastasis and histopathological grading. In the present study, we compared the expression of the subunit gamma2 of Laminin-5 under normal, dysplastic and invading epithelia in 65 biopsies previously diagnosed for oral squamous cell carcinoma. The number of gamma2-positive cells were analyzed in relation to patients' survival, tumor grading, size of the lesion, TNM stage, histopathological pattern of invasion and inflammatory reaction. Biopsies of oral squamous cell carcinomas were deparaffinised, processed for antigen unmasking procedures and stained with antibody anti-Laminin-5 gamma2. By light microscopy, 4 optical fields of x200 were selected in three different areas including normal, dysplastic and invading epithelia. Positive cells were counted and divided into three categories, which included <20 cells, between 21 and 50 cells and >50 stained cells. Patient survival was analyzed by Kaplan-Mayer curves. gamma2-positive cells were found in the basal layer of dysplastic epithelium, within inflammatory infiltrate, at the margins of differentiated invading islands and at the forefront of undifferentiated invading nests. Observations showed that an increased number of gamma2-positive cells correlated significantly with a shorter life expectancy under invading epithelia (log-rank test p<0.05), not when a count was performed under normal or dysplastic epithelia of the same patient. The number of gamma2-positive cells also correlated with the histopathological pattern of invasion. Our results show that gamma2 may be a reliable prognostic tool for oral squamous cell carcinomas.

Chemotherapy-induced myelosuppression by vinorelbine: a comparison between different dose schedules by simulation.

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to simulate the plasma profile and the toxicity of vinorelbine after multiple oral dose treatment to humans. The PK drug profile was described by a three-compartment open model linked to a PD model aimed to describe the drug toxicity on the circulating neutrophils. Different dose schedules were simulated holding the total administered dose constant (100 mg p.o. during two weeks): 7.7 mg daily (13 doses), 20 mg every 3 days (5 doses) and 33.3 mg every 6 days (3 doses). The lowest values of the circulating neutrophils were observed after 18 days from the start of the treatment and at nadir the fraction of the circulating neutrophils were 0.733, 0.703 and 0.681 after the three doses in decreasing order. These differences were not clinically significant, however the drug bioavailability, which was fixed to 0.35 in the simulation, might be highly variable among subjects contributing to a large extent to the observed variability in drug toxicity.

Classical and molecular analyses to characterize commercial dry yeasts used in wine fermentations.

AIMS: The aim of the work was to apply PCR-temperature gradient gel electrophoresis (PCR-TGGE) and restriction enzyme analysis (RE) assays to identify commercially available starters of Saccharomyces cerevisiae sensu stricto complex. METHODS AND RESULTS: To characterize an analysed pool of 62 active dry yeasts of different brands used in wine fermentation practices, classical microbiological tests were also performed as well as evaluation of contamination with lactic acid bacteria and non-Saccharomyces yeasts. PCR-TGGE and RE were used in order to provide fast and reliable methods to identify and differentiate enological yeasts. Proposed molecular methods enabled to identify particular strains within 36 h after colony isolation and directly from dry yeast suspension. CONCLUSIONS: The methods are highly recommended to obtain reliable results on yeast strain differentiation in a significantly shorter time if compared to classical fermentation tests. SIGNIFICANCE AND IMPACT OF THE STUDY: The obtaining of yeast strain differentiation in a short time and without plating is a good tool for a rapid discrimination among enological strains used as starters in enological practices.

Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past? A prospective, randomized clinicopharmacological study.

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. AIMS: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.

Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and intraperitoneal chemohyperthermic perfusion.

Over the last few years surgery on patients with abdominal malignancies has become more aggressive but the majority of patients present locoregional recurrence as peritoneal dissemination. Cytoreductive surgery followed by intraperitoneal chemohyperthermic perfusion (ICHP) has been described for treatment and prevention of locoregional cancer spread from various origins. This paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples with a UV-HPLC method. A compartmental model was used to fit the drug concentrations in plasma and perfusate. Our results showed a mean maximum plasma concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7 +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2) were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL) was estimated by fitting the data by a compartmental model and the mean value was 72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP in patients with peritoneal surface malignancies seems to have clinical value since it gives high peritoneal and tumor MMC concentrations with limited systemic exposure and toxicity.

[Guidelines for the management of HCV infection in HIV-infected patients. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani]. / Linee-guida per la gestione clinica della infezione/malattia da HCV nei pazienti con infezione da HIV.

It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

A short introduction to pharmacokinetics.

Phamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile may be well summarized by Cmax, Tmax, t 1/2 and AUC and, having more than one profile, 8 parameters at least, the mean and standard deviation of these parameters, may well summarize the drug kinetics in the whole population. A more carefull description of the data can be obtained interpolating and extrapolating the drug concentrations with some mathematical functions. These functions may be used to reduce all the data in a small set of parameters, or to verify if the hypotheses incorporated in the functions are confirmed by the observations. In the first case, we can say that the task is to get a simulation of the data, in the second to get a model. The functions used to interpolate and reduce the pharmacokinetic data are the multiexponential functions and the reference models are the compartmental models whose solutions are just the multiexponential functions. Using models, new meaningfull pharmacokinetic parameters may be defined which can be used to find relationships between the drug kinetic profile and the physiological process which drive the drug absorption, distribution and elimination. For example, compartmental models allow to define easily the clearance which is dependent on the drug elimination process, or the volume of distribution which depends on the drug distribution in the tissues. Models provide also an easy way to get an estimate of drug absorption after extravasculare drug administration (bioavailability). Model building is a complex multistep process where, experiment by experiment and simulation by simulation, new hypothesis are proven and disproven through a continuous interaction between the experimenter and the computer.

Sex-related variations in serum nerve growth factor concentration in humans.

A role of nerve growth factor (NGF) in the neuro-endocrine-immune interactions has been recently suggested by the presence of NGF and its receptors in cells of the immune and endocrine systems. The improvement in the comprehension of the role played by NGF in humans is linked to the availability of a sensitive and reliable method to quantify NGF concentrations in body fluids and tissues. As a consequence of different methods used, normal levels of human serum NGF reported in the literature show wide differences. The present results indicate that ELISA appears very sensitive (detection limit 1.4pg/ml) and allows the discrimination of subtle variations of serum NGF concentrations. ELISA performed in serum obtained from men indicated that NGF concentration was 40.8+/-10.8pg/ml, whereas women showed significantly lower levels that were influenced by the menstrual cycle. In particular, the mean value of this neurotrophin during the follicular phase was 8.2+/-1.4pg/ml; the luteal phase, in turn, showed levels up to 14.4+/-2.9pg/ml. The difference of serum NGF concentrations between the follicular and luteal phase in each woman was statistically significant. Differences in NGF concentrations between men and women (in both phases of the menstrual cycles) were also statistically significant. In conclusion, a possible role of sex steroids as modulators of NGF secretion in humans is strongly supported by the present paper. However, mechanisms underlying this phenomenon are still unknown. The evidence indicating physiological sex hormone-related variations in NGF levels would be of interest in view of the possible use of circulating NGF modifications as a laboratory biomarker in different diseases.

High incidence of hyperandrogenism-related clinical signs in patients with multiple sclerosis.

A mild prevalence of multiple sclerosis (MS) is present in females (2:1). To elucidate the pathogenetic role of sex steroids on the disease, we studied 76 women affected by MS, compared to 50 healthy women (mean age +/- SD, 34.9 +/- 0.9 vs. 33.4 +/- 1.7 years). The menarche was at mean age of 12.3 +/- 0.2 vs. 12.4 +/- 0.2. Interval between menses was 28.0 +/- 0.3 vs 27.8 +/- 0.3 days, with duration of menstrual flow of 5.0 +/- 0.2 vs. 5.0 +/- 0.2 days. Oligo- or amenorrhea was present in 20% of patients and in 16% of controls. Oral contraceptives were assumed by 21% of patients and 34% of controls (n.s.). Premenstrual symptoms were found in 43% of patients and in 46% of controls (n.s.). The incidence of hyperandrogenism (greasy skin, acne and hirsutism), evaluated by a specific questionnaire, was higher and statistically significant in MS patients than in controls (28% vs. 10%, p<0.05). Further studies, including a complete clinical and laboratory evaluation of gonadal function, are necessary in order to clarify whether hyperandrogenism may influence MS disease activity.

gammadelta T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapy.

gammadelta T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non-peptidic antigens was observed in human immunodeficiency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of gammadelta T-cell anergy in HIV+ positive patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on gammadelta T-cell functions. Peripheral gammadelta T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. gammadelta T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the Vdelta2/Vdelta1 ratio was inverted as a consequence of a decrease in Vdelta2 T-cell number. Moreover, IPP-stimulated Vdelta2 T cells from the HIV-OIC group displayed a major defect in interferon-gamma (IFN-gamma) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored gammadelta T-cell function. Accordingly, in vitro CD45RA depletion resulted in gammadelta T-cell hyporesponsiveness. Altogether, the incidence of gammadelta T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore gammadelta T-cell reactivity, extending the immune recovery to non-peptide microbial antigens.

[The correlations between color Doppler using a contrast medium and the neoangiogenesis of small prostatic carcinomas]. / Correlazioni tra color Doppler con uso di mezzo di contrasto e neoangiogenesi dei piccoli carcinomi prostatici.

PURPOSE: To investigate if the use of a contrast agent (Levovist) improves the specificity of US in the diagnosis of prostate carcinoma, having the results of prostate biopsy as the gold standard. MATERIAL AND METHODS: Thirty patients with physical findings suspicious for prostate carcinoma and PSA ranging 5 ng/mL to 15 ng/mL were examined with transrectal US (TRUS) integrated with the color Doppler mode and contrast agent administration (4 g injected at 4 mL/min: 300 mL concentration). RESULTS: Based on bioptic and surgical results, 14 prostate carcinomas were found, all of them < 1.2 cm. Conventional US recognized the suspected nodule in 11 cases, with 78% sensitivity and 93% specificity. Color Doppler showed color signals in 8/14 cases, which were peripheral to the lesion or intranodular, but did not add any important finding to those of gray-scale US. In contrast, contrast enhanced studies showed 13/14 carcinomas, which improved sensitivity significantly (92%). Particularly, 11/14 lesions had a typical avascular pattern within the strongly enhanced peripheral gland, while 2 small lesions only exhibited intranodular vessels. DISCUSSION AND CONCLUSIONS: We compared our results with the Microscopic Angiogenesis Grading System (MAGS) index and found it exceeded 30 in the 11 avascular lesions value indicates microneoangiogenesis. In the other two cases a value < 30 was correlated with a different type of tumor vascularization typical of macroangiogenesis.

Endoscopic optic nerve decompression for traumatic blindness.

OBJECTIVES: The goal of this study was to compare the outcome of patients with traumatic optic neuropathy (TON) treated with high-dose steroids with the outcome of patients with TON treated with endoscopic optic nerve decompression (EOND) after failing high-dose steroid treatment. METHODS: During this retrospective review of patients with TON seen from 1994 to 1998, all patients were first treated with megadose methylprednisolone for 48 hours. Patients with no improvement or with worsening visual acuity were offered EOND. RESULTS: Eleven of 34 (32%) patients treated with high-dose steroids showed improvement, and 23 (68%) did not. Seventeen of the 23 patients without improvement after high-dose steroid treatment underwent EOND. Fourteen of 17 (82%) surgically treated patients had improved visual acuity, and 3 (18%) did not, with an overall improvement in 25 of 34 (74%) patients (chi(2) = 11. 338, P = 0.0007). CONCLUSION: EOND is an appropriate treatment technique for patients with TON in whom high-dose steroid treatment has failed.