Characterization of an AA9 LPMO from Thielavia australiensis, TausLPMO9B, under industrially relevant lignocellulose saccharification conditions.

BACKGROUND: The discovery of lytic polysaccharide monooxygenases (LPMO) has changed our perspective on enzymatic degradation of plant biomass. Through an oxidative mechanism, these enzymes are able to cleave and depolymerize various polysaccharides, acting not only on crystalline substrates such as chitin and cellulose, but also on other polysaccharides, such as xyloglucan, glucomannan and starch. Despite their widespread use, uncertainties related to substrate specificity and stereospecificity, the nature of the co-substrate, in-process stability, and the nature of the optimal reductant challenge their exploitation in biomass processing applications. RESULTS: In this work, we studied the properties of a novel fungal LPMO from the thermophilic fungus Thielavia australiensis, TausLPMO9B. Heterologous expression of TausLPMO9B in Aspergillus niger yielded a glycosylated protein with a methylated N-terminal histidine showing LPMO activity. High sequence identity of the AA9 domain to that of MtLPMO9B (MYCTH_80312) from Myceliophthora thermophila (84%) indicated strictly C1-oxidizing activity on cellulose, which was confirmed experimentally by the analysis of products released from cellulose using HPAEC. The enzyme was stable and active at a pH ranging from 4 to 6, thus matching the conditions commonly used in industrial biomass processing, where a low pH (between 4 and 5) is used due to the pH-optima of commercial cellulases and a desire to limit microbial contamination. CONCLUSION: While the oxidative cleavage of phosphoric acid swollen cellulose (PASC) by TausLPMO9B was boosted by the addition of H2O2 as a co-substrate, this effect was not observed during the saccharification of acid pretreated corn stover. This illustrates key differences between the lab-scale tests with artificial, lignin-free substrates and industrial settings with lignocellulosic biomass as substrate.

Additive effects of salmeterol and fluticasone or theophylline in COPD.

BACKGROUND: ss(2)-Agonists and corticosteroids or theophylline can interact to produce beneficial effects on airway function in asthma, but this has not been established in COPD. METHODS: Eighty patients with well-controlled COPD were randomized to receive 3 months of treatment in one of four treatment groups: (1) salmeterol, 50 microg bid; (2) salmeterol, 50 microg, plus fluticasone propionate, 250 microg bid; (3) salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid; and (4) salmeterol, 50 microg, plus titrated theophylline bid. At each visit, a dose-response curve to inhaled salbutamol was constructed using a total cumulative dose of 800 microg. RESULTS: A gradual increase in FEV(1) was observed with each of the four treatments. Maximum significant increases in FEV(1) over baseline values that were observed after 3 months of treatment were as follows: salmeterol, 50 microg bid, 0.163 L (95% confidence interval [CI], 0.080 to 0.245 L); salmeterol, 50 microg, plus fluticasone propionate, 250 microg bid, 0.188 L (95% CI, 0.089 to 0. 287 L); salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid, 0.239 L (95% CI, 0.183 to 0.296 L); and salmeterol, 50 microg, plus titrated theophylline bid, 0.157 L (95% CI, 0.027 to 0. 288 L). Salbutamol always caused a significant dose-dependent increase in FEV(1) (p < 0.001), although the 800-microg dose never induced further significant benefit when compared with the 400-microg dose. The mean differences between the highest salbutamol FEV(1) after salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid, and that after salmeterol, 50 microg, plus titrated theophylline bid or salmeterol, 50 microg bid, were statistically significant (p < 0.05). CONCLUSION: These data show that both long-acting ss(2)-agonists and inhaled corticosteroids have a role in COPD. The data also show that fluticasone propionate and salmeterol given together are more effective than salmeterol alone. Moreover, it suggests that the addition of fluticasone propionate to salmeterol allows a greater improvement in lung function after salbutamol, although regular salmeterol is able to improve lung function in COPD patients without development of a true subsensitivity to its bronchodilator effect. In any case, patients must be treated for at least 3 months before a real improvement in lung function is achieved.

Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia.

OBJECTIVE: There are several reports of documented adverse cardiac effects during treatment with beta-agonists. Since one should be aware that this may be a problem in patients with preexisting cardiac disorders, we have conducted a randomized, single-blind, balanced, crossover, placebo-controlled study to assess the cardiac effects of two single doses of formoterol (12 microg and 24 microg) and one single dose of salmeterol (50 microg) in 12 patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia (PaO2<60 mm Hg). DESIGN: Each patient was evaluated at a screening visit that included spirometry, blood gas analysis, plasma potassium measurement, and 12-lead ECG. In following nonconsecutive days, all patients underwent Holter monitoring 24 h during each of the four treatments. Holter monitoring was started soon before drug administration in the morning. Plasma potassium level was measured before drug inhalation, at 2-h intervals for 6 h, and at 9, 12, and 24 h following administration. None of our patients took rescue medication during the 24-h period. RESULTS: Holter monitoring showed a heart rate higher after formoterol, 24 microg, than after formoterol, 12 microg, and salmeterol, 50 microg, and supraventricular or ventricular premature beats more often after formoterol, 24 microg. Formoterol, 24 microg, significantly reduced plasma potassium level for 9 h when compared with placebo, whereas formoterol, 12 microg, was different after 2 h and salmeterol, 50 microg, from 4 to 6 h. CONCLUSIONS: The results of this study suggest that if a COPD patient is suffering from preexisting cardiac arrhythmias and hypoxemia, long-acting beta-agonists may have adverse effects on the myocardium, although the recommended single dose of salmeterol and formoterol, 12 microg, allows a higher safety margin than formoterol, 24 microg.

A comparison of bronchodilating effects of salmeterol and oxitropium bromide in stable chronic obstructive pulmonary disease.

Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled beta 2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting beta 2-agonists but not for long-acting beta 2-agonists. Oxitropium bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium bromide, but with a longer-lasting effect. In the present study, the time course of inhaled oxitropium bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 micrograms salmeterol hydroxynaphthoate, 200 and 400 micrograms oxitropium bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than oxitropium. The response to salmeterol exceeded the response to 200 micrograms oxitropium for 12 h, but its responses were significantly (P < 0.05) greater than those to 200 micrograms oxitropium from 10 to 12 h. From 3 to 12 h, salmeterol also surpassed 400 micrograms oxitropium but differences were not significant (P < 0.05). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to 200 micrograms oxitropium bromide, but there was no significant difference (P < 0.05) between salmeterol and 400 micrograms oxitropium bromide. No significant changes in pulse rate, blood pressure or electrocardiograms were found among the four groups as compared with placebo group. These findings confirm and extend what has been demonstrated by the authors' previous studies, and show that salmeterol compares conveniently with anti-cholinergic drugs in terms of effects on lung function at clinically recommended doses.

Clinical significance of allergic sensitization to cockroaches in patients with mite related respiratory allergy.

The aim of our study was the evaluation of the clinical significance of allergic sensitization to cockroaches (C) in subjects with skin prick test (SPT) positivity only to mites, since we previously demonstrated a frequent association of SPT positivity between the allergens of these parasites. We studied 231 patients with mite related respiratory symptoms and living in the Naples area in order to obtain a highly homogeneous sample. All patients underwent anamnestic procedures, physical examination, SPT by using commercially available materials and an extract containing the whole bodies of three C. Specific C IgE assays were carried out only in C SPT positive patients. 34 of 231 subjects showed a SPT positivity to C allergens with a moderate/low degree of SPT responses and serum specific IgE levels. The results of this study confirm our previous report on the slight role of C as sensitizing agents of the respiratory tract in Southern Italy. Further studies should be carried out in subjects with a higher risk of environmental exposure by using better purified and standardized allergenic extracts. We suggest moreover to perform in vivo and in vitro diagnostic tests for C allergens in patients with perennial symptoms, especially in those with slight response to therapy, or potentially exposed to allergens of these insects.

Comparative study of dirithromycin and azithromycin in the treatment of acute bacterial exacerbations of chronic bronchitis.

We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

Squamous cell carcinoma of the renal pelvis with metastasis in a dog.

The gross and microscopical features of a squamous cell carcinoma of the renal pelvis in an 18-year-old dog are described. This is a rare tumour originating from transitional cells of the pelvis. The tumour, which invaded the renal parenchyma and capsule and the small intestinal wall, metastasized to the lungs. Tumour cells expressed cytokeratin 8 and were arranged in a pattern similar to that of a squamous cell carcinoma found elsewhere, with prickle cells and horny pearls. The tumour was not diagnosed clinically but was found at necropsy. The presence of pelvic calculi in this dog is suggested as a cause of transitional cell squamous metaplasia and malignant transformation.

[Allergic rhinitis due to cockroach antigenic components. An emerging pathology?]. / La rinite allergica da componenti antigenici di blatta. Una patologia emergente?

The aim of our study was the evaluation of the role of these insects as causative agents of perennial rhinitis. We studied 317 subjects of both sexes (175 F and 142 M) living in Naples area and examined consecutively in our Centre for perennial nasal symptoms of suspected IgE mediated aetiology. All patients underwent the following diagnostic procedures: anamnestic procedures by using an internal questionnaire, clinical examination, skin prick test by using commercially available allergenic extracts and an allergenic extract containing the whole bodies of Blattella germanica and orientalis, Periplaneta americana. Blood samples for specific IgE determinations and a rhinologic visit were also carried out in patients with cockroach skin Prick test positivity. 14 of 317 subjects, prevalently young males, presented a skin positivity to cockroach allergens. All patients showed a moderate low degree of cutaneous and a low degree of serologic sensitization to allergens of these insects. Our preliminary data seem to demonstrate a mild role of cockroaches as causative agents of perennial rhinitis in Naples area. Further studies are necessary for a more appropriate knowledge of this allergy.

Causas de cancelación del turno quirúrgico, en un servicio de cirugía general / Causes of cancellation of the surgical turn, in a general surgery service

La cancelación de procedimientos quirúrgicos en una sala de cirugía, afecta la productividad de la misma y ocasiona un impacto emocional en el paciente. Objetivo: determinar las principales causas de cancelación del turno quirúrgico, en el Servicio de Cirugía General del Hospital Dr. Francisco Antonio Rísquez, en el periodo 2006-2015. Métodos: se revisaron las planillas del plan quirúrgico diario de cirugía, en el área de quirófano y los libros de cancelación de acto quirúrgico del departamento de Cirugía del hospital. Resultados: en el Hospital "Dr. Francisco Antonio Risquez", se planificaron para acto quirúrgico del Servicio de Cirugía desde el 2006 al 2015; 2.872 pacientes, de los cuales se suspendieron 1.082 (37,67 %). Las causas específicas de las cancelaciones del turno quirúrgico fueron: ausencia de anestesiólogos: 613 pacientes (56,65%), prolongación del turno quirúrgico: 132 (12,20%), crisis hipertensiva: 81 (7,49%), aire acondicionado dañado: 47 (4,34%), ascensor averiado: 38 (3,51%), "otros": 36 (3,33%), falta de material quirúrgico: 33 (3,05%), ausencia delespecialista en cirugía: 31 (2,87%), maquina anestésica dañada: 27 ( 2,50%), enfermedad aguda del paciente: 20 (1,85%), área quirúrgica contaminada: 14 (1,29%) y exámenes preoperatorios incompletos: 10 (0,92%). Por causas atribuidas al personal médico 666 (61,55 %) casos, seguidas por las inherentes a la institución 306 (28,28 %) personas y 110 (10,17 %) suspensiones atribuibles al paciente. Conclusiones: el índice de suspensión de cirugías en el período evaluado en nuestro centro fue muy alto. Las principales causas de cancelación del turno quirúrgico fueron atribuibles al personal médico(AU)

the cancellation of surgical procedures in a surgery room affects the productivity of the same and causes an emotional impact on the patient. Objective: to determine the main causes of cancellation of surgical interventions in the department of General Surgery of "Dr. Francisco Antonio Rísquez" Hospital, during the period comprised between 2006 and 2015. Methods: the daily surgical schedule formats were revised, located on the fourth floor in the operating room area, as well as the books detailing the cancellation of interventions by the department of Surgery, located in the hospital's office of medical records. Results: in "Dr. Francisco Antonio Rísquez" Hospital, 2.872 patients were scheduled for intervention by the department of surgery between the years 2006 and 2015, of which 1.082 (37, 67%) The specific causes behind the cancellation of the interventions were: absence of anesthesiologist: 613 (56,65%), prolonged surgery times: 132 (12,20%), hypertensive crisis: 81 (7,49%), malfunctioning air conditioning: 47 (4,34%), elevator out of order: 38 (3,51%), others: 36 (3,33%), lack of surgical equipment: 33 (3,05%), absence of attending surgeon: 31 (2,87%), patient with acute illness: 27 (2,50%), non-operative anesthesia machinery: 20 (1,85%), contaminated operating room: 14 (1,29%) and incomplete preoperatory exams: 10 (0,92%). Causes attributed to medical staff predominated by 666 (61, 55%) cases, followed by causes attributed to the hospital in 306 (28, 28%) people, and 110 (10, 17%) suspensions attributed to the patient. Conclusions: the rate of suspension of surgeries in our center was very high and therefore worrisome for all health personnel. The main causes of cancellation of the surgical shift were attributable to medical personnel(AU)

A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease.

Bronchodilator efficacy of salbutamol (200 micrograms), salmeterol (50 micrograms) and ipratropium bromide (40 micrograms) aerosols has been compared in 16 patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind placebo controlled cross-over design. When absolute changes in FEV1 were used as the response criterion, efficacy of the three drugs was significantly better than placebo (P < 0.05). The onset of bronchodilatation after ipratropium bromide was slower than after salbutamol, but ipratropium induced more and longer-lasting bronchodilatation than the adrenergic drug. Salmeterol was slower but its duration was longer than salbutamol. The onset of the effect of salmeterol was slower than ipratropium bromide, but salmeterol showed, on average, superior bronchodilator efficacy compared with the anticholinergic agent, sustaining bronchodilation longer than ipratropium bromide (responses to salmeterol were significantly (P < 0.05) greater than those to ipratropium bromide from 4-12 h time period, but from 15 min to 1 h time periods response to ipratropium bromide exceeded salmeterol). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to ipratropium bromide and salbutamol. Moreover, the mean FEV1 area under the curve after ipratropium bromide was significantly (P < 0.05) higher than that after salbutamol. In any case, our data showed individual differences in patient response. We conclude that salmeterol compares favourably with ipratropium bromide in terms of effects on lung function at clinically recommended doses because it has a longer duration of action than ipratropium bromide. The longer dosing intervals, which may enhance compliance, encourage its administration in patients with COPD.

Oral bambuterol compared to inhaled salmeterol in patients with partially reversible chronic obstructive pulmonary disease.

OBJECTIVE: There is now good evidence that inhaled salmeterol is an effective agent in chronic obstructive pulmonary disease (COPD),but, at the present time, data on the effects of bambuterol, which is an oral tarbutaline pro-drug, in patients with COPD are scarce. Moreover, no comparative study between bambuterol and salmeterol in patients with chronic obstructive airway disorders has been published. The objective of this research was, consequently, to compare the efficacy and safety of 20 mg oral bambuterol and 50 microg inhaled salmeterol in patients with partially reversible COPD. METHODS: The speed and length of bronchodilation with 20 mg bambuterol and 50 microg inhaled salmeterol were compared in 16 patients with partially reversible COPD. The investigation and designed as a double-blind, double-dummy, cross-over, placebo controlled and randomised study. Lung function (FEV1, FVC) and systemic variables (subjective tremor, heart rate, blood pressure) were monitored prior to the administration of the drug and for 12 h after each agent on 3 non-consecutive days. RESULTS: Inhalation of salmeterol induced a significant (P < 0.05) increase of lung function when compared with placebo. In addition, oral bambuterol elicited good bronchodilation, with its maximum slightly later than for salmeterol. The mean (+/- SE) AUC(0-12h)S for all patients were 3.134 1 +/- 0.553 for salmeterol and 1963 1 +/- 0.573 for bambuterol. Both AUC(0-12h)S were significantly greater than for placebo (P < 0.05), but there was no significant difference (P = 0.077) between the salmeterol and bambuterol AUC(0-12h)S. Bambuterol, but not salmeterol, caused tremor in four patients. Moreover, it induced a higher heart rate when compared with salmeterol at each considered time after the administration of the drug; differences after 9 and 12 h were statistically significant (P < 0.05). CONCLUSION: Both oral bambuterol and inhaled salmeterol resulted in good bronchodilation in patients with stable COPD. However, bambuterol, but not salmeterol, caused tremor in several subjects and elicited a more pronounced tachycardia.

Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD.

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.