Valorization of agro-industrial wastes to produce hydrolytic enzymes by fungal solid-state fermentation.

Nowadays, significant amounts of agro-industrial wastes are discarded by industries; however, they represent interesting raw materials for the production of high-added value products. In this regard, orange peels (ORA) and exhausted sugar beet cossettes (ESBC) have turned out to be promising raw materials for hydrolytic enzymes production by solid state fermentation (SSF) and also a source of sugars which could be fermented to different high-added value products. The maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the enzymatic extracts obtained after the SSF of ORA were 31,000 U·kg-1 and 17,600 U·kg-1, respectively; while for ESBC the maximum values reached were 35,000 U·kg-1 and 28,000 U·kg-1, respectively. The enzymatic extracts obtained in the SSF experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore, it was found that extracts obtained from SSF of ORA, supplemented with commercial cellulase, were more efficient for the hydrolysis of ORA and ESBC than a commercial enzyme cocktail typically used for this purpose. In this case, maximum reducing sugars concentrations of 57 and 47 g·L-1 were measured after the enzymatic hydrolysis of ESBC and ORA, respectively.

The rs2108622 polymorphism is related to the early risk of ischemic stroke in non-valvular atrial fibrillation subjects under oral anticoagulation.

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

Adherence to hormone therapy in patients with mCRPC: psychometric validation of the A-HT questionnaire.

Abstract: The incidence rate of prostate cancer (PCa) in many Western countries is high, contributing greatly to the cancer disease bur-den. In most cases, patients progress to metastatic disease defined as castration-resistant prostate cancer after androgen deprivation (mCRPC) following primary treatment where the majority of patients receive first-line new-generation oral hormonal therapies (HT) such as Abiraterone Acetate (AA) and Enzalutamide (ENZ). Despite the importance of correct intake of these drugs, adherence in patients with mCRPC is still poorly investigated and managed with measures not specific to this population. A self-report questionnaire was developed and validated with women with breast cancer treated with oral HT (A-BET). Therefore, this study aims to test the psychometric properties of this instrument on patients with mCRPC treated with AA or ENZ. A prospective observational validation study. The questionnaire was completed by all participants and again after 7/10 days by a randomized subsample to assess stability. Sixty-six patients completed the study (mean age of 72.8 years) and 31 completed the re-test (mean age of 72.7 years). Content validity reported excellent results. Cronbach's alpha of each item showed a strong correlation. Validation of an instrument to measure adherence to HT in patients with mCRPC can be a valuable tool for health professionals involved in patient care. In addition, having a population-specific validated instrument allows to make comparisons between results from different observations.

The interaction between Environmental Enrichment and fluoxetine in inhibiting sucrose-seeking renewal in mice depend on social living condition.

RATIONALE: Several single or combined therapeutic approaches have been developed to treat addiction, however with partial efficacy in preventing relapse. Recently, the living environment has been suggested as a critical intervening factor determining the treatment outcomes. Despite accumulating evidence confirming a role of living conditions in the vulnerability to addictive behaviours, their impact on single or integrative therapeutic strategies preventing relapse is yet to be identified. OBJECTIVES: Here, we explore the possible interaction between brief Environmental Enrichment (EE) exposure and acute fluoxetine administration in inhibiting sucrose-seeking behaviours, and whether this effect could be affected by living environment. METHODS: Social and isolated adult male C57BL/6 mice were trained to sucrose self-administration associated to a specific conditioning context (CxA), followed by a 7-day extinction in a different context (CxB). Afterwards, mice were exposed for 22 h to EE and then injected with fluoxetine (10 mg/kg, i.p.) 1 h before a CxA-induced sucrose-seeking test. RESULTS: Brief EE exposure and acute fluoxetine administration alone inhibited context-induced sucrose-seeking in both housing conditions; however, they exhibited additive properties only in social condition. CONCLUSIONS: Our data show that social environment may influence the EE/fluoxetine interaction in inhibiting relapse to sucrose. These findings suggest that setting up proper living conditions to boost the efficacy of therapeutic approaches may represent a fundamental strategy to treat addiction disorders.

Valorization of exhausted sugar beet cossettes by successive hydrolysis and two fermentations for the production of bio-products.

Exhausted sugar beet cossettes (ESBC) show an enormous potential as a source of sugars for the production of bio-products. Enzyme hydrolysis with the combined effect of mainly cellulases, xylanases and pectinases, turned out to be very efficient, obtaining almost double the concentration of sugars measured with the sole action of Celluclast® and ß-glucosidase, and increasing 5 times the hydrolysis rate. As the sole pretreatment, ESBC soaked in the hydrolysis buffer were autoclaved, avoiding the application of severe conventional biomass pretreatments. Moreover, a promising alternative for the complete utilization of glucose, xylose, arabinose, mannose and maltose contained in ESBC is proposed in this paper. It consists of sequential fermentation of sugars released in the hydrolysis step to produce bioethanol and lactic acid as main bio-products. Compared to separate fermentations, with this strategy glucose and hemicellulose derived sugars were completely consumed and the 44% of pectin derived sugars.

Value of the determination of TNF-alpha in the plasma of patients with non-Hodgkins lymphoma.

The present report describes the value of the plasma determination of TNF-alpha, at diagnosis, in 43 patients with non-Hodgkin's lymphoma (NHL), related to their clinical presentation and the new International Prognosis Index (IPI). We also compare the levels of TNF-alpha with those of LDH, beta-2-microglobulin (beta-2-m), and ferritin. At diagnosis, the mean values of the quotients between the marker values and the maximum value of normal (ratio:r-) are placed 7 times higher than normal for r-TNF-alpha, whereas those of r-beta-2-m and r-LDH are 2,4 and 1,4 times more respectively. We found a relationship between the value of r-TNF-alpha and the ECOG, Ann Arbor stage, the number of affected extranodal sites, and between the values of r-beta-2-m with r-LDH. The best correlation was obtained between the values of r-TNF-alpha and r-beta-2-m and IPI, however r-TNF-alpha best stratify the four risk groups in this prognosis index.

Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause.

Estrogen receptors (ERs), progesterone receptors (PRs), and P29, an ER-associated protein, were studied immunohistochemically in human cervix with use of specific monoclonal antibodies. In ectocervical epithelium, homogeneous staining was found for P29 throughout the menstrual cycle and after menopause. Weak or moderate staining was found for ER in the basal and, occasionally, the parabasal layers of ectocervix during the proliferative phase. In contrast, staining decreased in secretory phase and postmenopausal epithelia. Staining was negative for PR in all the exocervical epithelia. Heterogeneous staining, more pronounced for P29, was found for the three antigens of the study in endocervical epithelium. Staining did not change with the hormonal status of patients, except for ER, where staining decreased during the secretory phase. Stromal cells were negative or weakly positive, whereas muscular fibers were positive. This study suggests that the capacity of response of the steroid apparatus of cervical cells to fluctuations of circulating estrogens and progestins is limited compared with some of the cell functions, such as mucus secretion, or with other target tissues, such as endometrium. Additionally, the differences found in the pattern of expression of the three antigens studied suggest that the steroid-dependent growth and differentiation in ectocervix is regulated differently to endocervix.

Multiwire proportional chamber system of the Fermilab single arm spectrometer.

We describe a system of two groups of multiwire proportional chambers and its special purpose interface used in the Single Arm Spectrometer (SAS) facility at Fermilab. The first set measures the coordinates of the fast particle going into the spectrometer arm with a space resolution down to +/-0.5 mm. The second set, close to the target, measures the multiplicity and angular distributions of charged particles coming from the interaction. The chambers of this set have three sensitive planes with wires at 120 degrees in the same gas volume to measure three coordinates for each physical point, two readout channels per wire to minimize the inefficiency due to the very high flux and insensitive regions at the center of the chambers where they are crossed by the beam.

[Correlation between functional and radiographic data, and broncho-alveolar cytology in patients with diffuse interstitial lung disease]. / Correlazioni fra dati funzionali, radiografici e cellularità bronchiolo-alveolare in pazienti affetti da pneumopatie interstiziali diffuse.

BACKGROUND: "Interstitial Lung Disease" is a term that includes a heterogeneous group of disorders characterized by variable degrees of parenchymal inflammation (alveolitis) and fibrosis. Alveolitis represents one of the most important aspects of ILD and its characterization by broncho-alveolar lavage (BAL) can give explanations of the different clinical features, in association with the evaluation of physiological changes and High Resolution Computed Tomography (HRCT). The aim of this study was to establish a correlation between variations in broncho-alveolar cells and anatomical-functional alterations in patients affected by ILD before and after corticoid therapy. METHODS: Thirty-one patients (14 males 17 females) were introduced in the study and were evaluated for clinical signs, functional parameters, HRCT and cyto-immunological aspects of BAL fluid. All data were acquired at the admission in the study, after 60 and 180 days. Patients had received prednisone 1 mg/kg/die for 60 days and, then, 0.25 mg/kg/die for 120 days. RESULTS: In lymphocyte alveolitis, a clinical-radiological improvement was frequently observed after therapy while in those with neutrophilic and eosinophilic components, no improvement was detected. CONCLUSIONS: In conclusion, BAL represents a useful tool in qualifying ILD which can be easily monitored by clinical, functional and radiological data. Therefore, a new method for the diagnosis and monitoring of ILD is suggested. This method has the marked advantage to reach a reliable diagnosis even in a high percentage of patients who refuse or can not undergo the biopsy assay.

Interposition of the first jejunal loop for reconstruction after total gastrectomy.

A new technique of reconstruction after total gastrectomy by interposing the first jejunal loop between the esophagus and the duodenum, is described. Vascular and neural integrity of the interposed intestinal segment is "guaranteed", resulting in acceptable muscular activity on intestinal contents and partial digestive function, with limited post-operative complications. The interposed jejunal loop assumes reservoir function and permits almost normal eating habits. Application of this technique to 18 patients undergoing total gastrectomy has resulted in a more than satisfactory post-operative functional and nutritional status over a one to 14 year follow-up period.

Comparison of intra-operative analgesia provided by intravenous regional anesthesia or brachial plexus block for pancarpal arthrodesis in dogs.

The aim of this study was to compare intravenous regional anesthesia (IVRA) and brachial plexus block (BPB) for intra-operative analgesia in dogs undergoing pancarpal arthrodesis (PA). Twenty dogs scheduled for PA were intramuscularly sedated with acepromazine (0.03 mg/kg), general anesthesia was intravenously (IV) induced with thiopental (10 mg/kg) and, after intubation, maintained with isoflurane in oxygen. In 10 dogs (GIVRA) IVRA was performed on the injured limb administering 0.6 ml/kg of 0.5% lidocaine. In 10 dogs (GBPB) the BPB was performed at the axillary level with the help of a nerve stimulator and 0.3 ml/kg of a 1:1 solution of 2% lidocaine and 1% ropivacaine was injected. During surgery fentanyl (0.002 mg/kg IV) was administered if there was a 15% increase of HR and/or MAP compared to the values before surgical stimulation. All the standard cardiovascular and respiratory parameters were continuously monitored during surgery. The duration of surgery and the time of extubation were recorded. Data were compared with a 1-way ANOVA test (P<0.05). No patients required fentanyl administration during surgery. All the recorded parameters were similar in the two groups. The two techniques were similar in providing intra-operative analgesia in dogs undergoing orthopaedic surgery.

Alveolar recruiting maneuver in dogs under general anesthesia: effects on alveolar ventilation, gas exchange, and respiratory mechanics.

The aim of this study was to evaluate the effects of a recruiting maneuver (RM) on lung aeration, gas exchange, and respiratory mechanics during general anesthesia in mechanically ventilated dogs. A thoracic computed tomography (CT) scan, an arterial blood sample, and measurement of respiratory mechanics were performed 10 min before (baseline) and both 5 and 30 min after a vital capacity RM in 10 dogs under general anesthesia. The RM was performed by inflating the lung at 40 cm H(2)O for 20 s. Lung aeration was estimated by analyzing the radiographic attenuation of the CT images. Lung aeration and gas exchange improved significantly 5 min after the RM compared to baseline and returned to values similar to baseline by 30 min. Static lung compliance was not significantly affected by the RM. An RM induces a temporary improvement in lung function in healthy dogs under general anesthesia.

[Carcinoid of the ileum. Presentation of 5 cases]. / Il carcinoide ileale. Osservazione di 5 casi.

Ileal carcinoid is an infrequent pathology that may present clinically in a highly varied way. It may be completely asymptomatic and present acutely with occlusion or haemorrhage, or it may present with an unmistakable symptomatology of carcinoid syndrome. Clinical aspects are discussed together with possibilities of treating the primary lesions and metastases. Five cases observed in the past 7 years are reported.

[Clinical use of recombinant IFN alfa-2b in the treatment of primary cancer of the lung (preliminary results)]. / Uso clinico dell'IFN alfa-2b ricombinante nel trattamento del cancro primitivo del polmone (risultati preliminari).

In the period between January 1986 and December 1989 we have studied 60 patients with primitive lung cancer, subdivided in 3 groups according to the therapy: 20 were treated with surgery therapy, 20 with radiotherapy, 20 with chemotherapy. We have been studying a second group since September 1989; this is composed, until now, by 30 patients, subdivided in three groups as above. To each group we added alfa-2b recombinant Interferon at the dose of 3,000,000 i.m. three times a week for three months. We repeated the same therapy after three months. We have demonstrated that the combination alfa-2b recombinant interferon and the surgery therapy, radiotherapy and chemotherapy in patients with primitive lung cancer, can improve the quality of life but it doesn't prolong the duration of life.

Prevalence of phenotypic activated protein C resistance (APCR) in venous thromboembolic patients.

Until the discovery of activated protein C resistance (APCR), less than 10% of patients with venous thromboembolism (VT) showed defects in proteins involved in the inhibition of coagulation. APCR is caused by a single point mutation in the factor V gene, and it is accepted that APCR is associated with an increased risk for VT. In this work, we studied the prevalence of APCR in venous thromboembolic patients and found it to be 10.5% compared with 4.5% in controls (p = 0.105).

Distribution of involucrin in normal and pathological human uterine cervix.

A study was undertaken to determine the potential value of involucrin immunostaining, a protein synthesized by mature squamous epithelial cells, in distinguishing benign from neoplastic lesions in cervical pathology. A total of 146 cervical biopsies were analyzed using an indirect immunoperoxidase method and polyclonal antibody. A suprabasal homogeneous cytoplasmic staining pattern was consistently observed in normal squamous cervical epithelium. In contrast, 43.7% of cervical condylomas showed involucrin at all levels of the epithelium including the basal layer. Variable patterns were seen in cervical intraepithelial neoplasia (CIN), with 46% of full-thickness stainings, although no significant difference was obtained among the different grades of CIN lesions. Distribution of involucrin was correlated (P less than 0.05) with the degree of tumor differentiation in squamous cell carcinomas, being absent in 71.4% of poorly differentiated carcinomas and focally present in 75% of well-differentiated carcinoma. Lesions of endocervical origin, either benign or malignant, were entirely negative for involucrin. It is concluded that involucrin seems unable to establish a reliable differential diagnosis between benign and neoplastic conditions in cervical pathology, and should therefore be considered only a specific marker of squamous differentiation in both normal and pathological human uterine cervix.