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1.
Phytother Res ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489735

RESUMO

Isocordin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 were evaluated for their cytotoxicity effect against human melanoma cells (A2058). Analogues 4, 5, and 6 showed a higher inhibitory activity with IC50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively. These analogues, 4, 5, and 6, also induced an apoptotic response at 12.5- and 25-µM concentrations. They inhibited the expression of antiapoptotic proteins Bcl-2 and Hsp70, a critical factor that promotes tumour cell survival. In contrast, Bax and caspase-9 expression, and caspase-3 enzyme resulted activated. These results were correlated to a DNA fragmentation typical of apoptosis and an increase of intracellular reactive oxygen species (ROS) levels. Alternatively, at higher concentration (50 µM), when the capacity of the cells to sustain Hsp70 synthesis is reduced, our results seem to indicate that necrosis was induced by a further increase in ROS production. Therefore, the central finding in the present study is that these molecules downregulates Hsp70 expression. Altogether, these results suggest that 4-oxyalkyl-isocordoin analogues 4, 5, and 6 deserve to be deeply investigated for a possible application as Hsp70 inhibitor in the management of melanoma.

2.
Clin Exp Med ; 19(3): 357-366, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989453

RESUMO

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

3.
Chem Biol Interact ; 305: 79-85, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30935903

RESUMO

Melanoma is a highly invasive cancer that resists most conventional treatments. Therefore, there is an urgent need to identify alternative anticancer agents able to affect new molecular targets. Drimys winteri (Winteraceae) is a medicinal plant, employed in Brazil and many countries, in folk medicine against a variety of ailments, especially for the treatment of fevers, ulcers, pains, affections of respiratory tract and cancers. Previous phytochemical studies have isolated and identified the presence of diverse classes of secondary metabolites in this plant such as sesquiterpenes. In an ongoing to identify new natural anticancer compounds for the treatment and/or prevention of melanoma, we study the effects of Drimys winteri bark ethyl acetate extract and its sesquiterpenes drimenol, nordrimenone, isonordrimenone and polygodial on human melanoma cells. The treatment of melanoma cells with extract, drimenol, isordrimenone and polygodial resulted in a significant reduction in cell viability. But, polygodial showed the highest inhibitory growth activity. In addition, we reported an apoptotic response after treatment with drimenol, isordrimenone and polygodial that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of caspase cascade at higher concentrations, correlated with additional reactive oxygen species increase, probably switches natural product-induced cell death from apoptosis to necrosis. Therefore, this evidence provides a scientific support for the anticancer employ of Drimys winteri in traditional medicinal and suggests that active molecules can be considered potential candidates to be tested also in in vivo models, alone or in combination with chemotherapy agents, for the management of melanoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Drimys/química , Extratos Vegetais/química , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Drimys/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/patologia , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/farmacologia , Plantas Medicinais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/farmacologia
4.
Sci Rep ; 9(1): 4996, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30899033

RESUMO

Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.

5.
Arthritis Rheumatol ; 71(6): 1000-1010, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30592383

RESUMO

OBJECTIVE: To assess the composition of gut microbiota in Italian and Dutch patients with juvenile idiopathic arthritis (JIA) at baseline, with inactive disease, and with persistent activity compared to healthy controls. METHODS: In a multicenter, prospective, observational cohort study, fecal samples were collected at baseline from 78 Italian and 21 Dutch treatment-naive JIA patients with <6 months of disease duration and compared to 107 geographically matched samples from healthy children. Forty-four follow-up samples from patients with inactive disease and 25 follow-up samples from patients with persistent activity were analyzed. Gut microbiota composition was determined by 16S ribosomal RNA-based metagenomics. Alpha- and ß-diversity were computed, and log ratios of relative abundance were compared between patients and healthy controls using random forest models and logistic regression. RESULTS: Baseline samples from Italian patients showed reduced richness compared to healthy controls (P < 0.001). Random forest models distinguished between Italian patient baseline samples and healthy controls and suggested differences between Dutch patient samples and healthy controls (areas under the curve >0.99 and 0.71, respectively). The operational taxonomic units (OTUs) of Erysipelotrichaceae (increased in patients), Allobaculum (decreased in patients), and Faecalibacterium prausnitzii (increased in patients) showed different relative abundance in Italian patient baseline samples compared to controls after controlling for multiple comparisons. Some OTUs differed between Dutch patient samples and healthy controls, but no evidence remained after controlling for multiple comparisons. No differences were found in paired analysis between Italian patient baseline and inactive disease samples. CONCLUSION: Our findings show evidence for dysbiosis in JIA patients. Only patient/control status, age, and geographic origin appear to be drivers of the microbiota profiles, regardless of disease activity stage, inflammation, and markers of autoimmunity.

6.
PLoS One ; 13(12): e0208171, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521551

RESUMO

BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications. OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability. METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis. RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection. CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.

7.
Otol Neurotol ; 39(10): e1026-e1033, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30212428

RESUMO

INTRODUCTION: External auditory canal cholesteatomas (EACC) is insidious in nature and rare entity. There are only few case series on EACCs and surgical strategy is not standardized. OBJECTIVES: 1) To elucidate etiology of EACC and cardinal features. 2) To suggest a practical staging of EACC. 3) To enumerate surgical management according to stage of EACC. STUDY DESIGN: Retrospective study in a quaternary referral center of 31 consecutive cases of EACC. RESULTS: Thirty-one patients with EACC were reviewed. Unilateral otorrhea 19 (61.2%), hearing loss 22 (70.9%), and otalgia 8 (25.8%) are cardinal symptoms. Sixteen primary and 15 secondary EACCs were treated. Bone erosion was observed in 20 cases. In the present series, stage III = 12 (38.7%), stage II = 8 (25.8%), stage I = 11 (35.4%) underwent definitive treatment by surgery. Canalplasty with reconstruction was done in 19 cases of stages I and II. Of 12 cases in stage III, 3 cases underwent canalplasty with reconstruction. Subtotal petrosectomy was done in five cases. Intact canal wall mastoidectomy with canalplasty in two cases and radical mastoidectomy in two cases. Fascia, cartilage, muscle, and bone dust were used for reconstruction. Median follow-up period was 6 years and no recurrence of cholesteatoma was observed. CONCLUSION: EACC is unique entity. Intraoperative and radiological findings assist in correct and practical staging of EACC. Late stage presentations of EACC are common. Definitive surgical treatment in our series avoided recurrence of cholesteatoma.

8.
G Ital Cardiol (Rome) ; 19(9): 488-494, 2018 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-30087509

RESUMO

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic coronary artery pathology and an important cause of coronary artery disease in young women with an average age of 40 to 50 years with few or no cardiovascular risk factors. There has been a surge in the diagnosis of SCAD due to an increased use of coronary angiography and the clinical availability and application of high-resolution intracoronary imaging. SCAD is due to the separation of coronary wall layers with the formation of intramural hematoma, compression of the true lumen and secondary myocardial ischemia. Coronary angiography is the first-line imaging, also useful are intravascular ultrasound and optical coherence tomography. Therapy is conservative in most cases because of the high percentage of spontaneous healing of the vascular wall. The prognosis is good, although the disease is burdened by a high prevalence of major adverse coronary events, including recurrence of coronary dissection, thus making careful follow-up essential in survivors of the acute event. Given that the presence of SCAD may be associated with aneurysm formation and dissections of other arteries, screening of the arterial tree may be useful, especially of the supra-aortic trunks and splanchnic circulation.

9.
Front Microbiol ; 9: 1210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29922272

RESUMO

Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.

10.
Chem Commun (Camb) ; 54(55): 7613-7616, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29926854
11.
Bioorg Med Chem ; 26(14): 3953-3957, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29934219

RESUMO

The natural product magnolol (1) and a selection of its bioinspired derivatives 2-5, were investigated by Inverse Virtual Screening in order to identify putative biological targets from a panel of 308 proteins involved in cancer processes. By this in silico analysis we selected tankyrase-2 (TNKS2), casein kinase 2 (CK2) and bromodomain 9 (Brd9) as potential targets for experimental evaluations. The Surface Plasmon Resonance assay revealed that 3-5 present a good affinity for tankyrase-2, and, in particular, 3 showed an antiproliferative activity on A549 cells higher than the well-known tankyrase-2 inhibitor XAV939 used as reference compound.

12.
Front Microbiol ; 9: 675, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29686658

RESUMO

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and ß-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

13.
Int J Mol Sci ; 19(5)2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29693574

RESUMO

The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.


Assuntos
Farmacorresistência Bacteriana , Microbioma Gastrointestinal , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Feminino , Humanos , Lactente , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Complicações Pós-Operatórias/tratamento farmacológico
14.
Sci Rep ; 8(1): 1709, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29374167

RESUMO

Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone deeply involved in the complex network of cellular signaling governing some key functions, such as cell proliferation and survival, invasion and angiogenesis. Over the past years the N-terminal protein domain has been fully investigated as attractive strategy against cancer, but despite the many efforts lavished in the field, none of the N-terminal binders (termed "classical inhibitors"), currently in clinical trials, have yet successfully reached the market, because of the detrimental heat shock response (HSR) that showed to induce; thus, recently, the selective inhibition of Hsp90 C-terminal domain has powerfully emerged as a more promising alternative strategy for anti-cancer therapy, not eliciting this cell rescue cascade. However, the structural complexity of the target protein and, mostly, the lack of a co-crystal structure of C-terminal domain-ligand, essential to drive the identification of new hits, represent the largest hurdles in the development of new selective C-terminal inhibitors. Continuing our investigations on the identification of new anticancer drug candidates, by using an orthogonal screening approach, here we describe two new potent C-terminal inhibitors able to induce cancer cell death and a considerable down-regulation of Hsp90 client oncoproteins, without triggering the undesired heat shock response.

15.
Int J Mol Sci ; 19(1)2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351194

RESUMO

Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145). The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify necrosis cell death. Genomic DNA, caspase-3 activity, expression of cleaved caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) proteins were analyzed in order to study the apoptotic process. The role of reactive oxygen species in cell death was also investigated. We found that the three essential oils, containing caryophyllene oxide as a main constituent, are capable of reducing the growth of human prostate cancer cells, activating an apoptotic process and increasing reactive oxygen species generation. These results suggest it could be profitable to further investigate the effects of these essential oils for their possible use as anticancer agents in prostate cancer, alone or in combination with chemotherapy agents.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Óleos Voláteis/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Óleos Voláteis/química , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Espécies Reativas de Oxigênio/metabolismo , Salvia/química , Proteína X Associada a bcl-2/genética
16.
J Neurosurg ; 128(2): 631-638, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28387625

RESUMO

OBJECTIVE The aim in this study was to review the technique and outcomes of cable graft interpositioning of the facial nerve (FN) in lateral skull base surgeries. METHODS The authors retrospectively evaluated data from patients who had undergone cable graft interpositioning after nerve sacrifice during skull base tumor removal between June 1987 and May 2015. All patients had undergone lateral skull base approaches to remove tumors at a quaternary referral center in Italy. Facial nerve function was evaluated before and after surgery using the House-Brackmann (HB) grading system. RESULTS Two hundred thirteen patients were eligible for study. The mean follow-up was 44.3 months. The most common pathology was vestibular schwannoma (83 cases [39%]), followed by FN tumor (67 cases [31%]). Facial nerve tumors had the highest incidence of nerve interruption (67 [66%] of 102 cases). Preoperative FN function was normal (HB Grade I) in 105 patients (49.3%) and mild (HB Grade II) in 19 (8.9%). At the last postoperative follow-up, 108 (50.7%) of the 213 patients had recovered to Grade III nerve function. Preoperative HB grading of the FN was found to have a significant effect on outcome (p = 0.002). CONCLUSIONS Cable graft interpositioning is a convenient and well-accepted procedure for immediate restoration of the FN. The study results, over a large number of patients, showed that the stitch-less fibrin glue-aided coaptation technique yields good results. The best possible postoperative result achieved was an HB Grade III. The chances of a good postoperative result increase when FN function is normal preoperatively. Slow-growing tumors of the cerebellopontine angle had a favorable outcome after grafting.

17.
Neurosurgery ; 83(4): 740-752, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029275

RESUMO

BACKGROUND: Intrinsic tumors of the facial nerve are a rare entity. Dealing with this subset of tumors is challenging both in terms of decision making and surgical intervention. OBJECTIVE: To review the outcomes of surgical management of facial nerve tumors and cable nerve graft interpositioning. METHODS: A retrospective analysis was performed at a referral center for skull base pathology. One hundred fifteen patients who were surgically treated for facial nerve tumors were included. In case of nerve interruption during surgery, the cable nerve interpositioning technique was employed wherein the facial nerve palsy lasted for less than 1-yr duration. In cases of facial nerve palsy lasting for greater than 1 yr, the nerve was restituted by a hypoglossal facial coaptation. RESULTS: Various degrees of progressive paralysis were seen in 84 (73%) cases. Sixty nine (60%) of the tumors involved multiple segments of the facial nerve. Sixty-two (53.9%) tumors involved the geniculate ganglion. Seventy four (64.3%) of the cases were schwannomas. Hearing preservation surgeries were performed in 60 (52.1%). Ninety one (79.1%) of the nerves that were sectioned in association with tumor removal were restituted primarily by interposition cable grafting. The mean preoperative House-Brackmann grading of the facial nerve was 3.6. The mean immediate postoperative grading was 5.4, which recovered to a mean of 3.4 at the end of 1 yr. CONCLUSION: In patients with good facial nerve function (House-Brackmann grade I-II), a wait-and-scan approach is recommended. In cases where the facial nerve has been interrupted during surgery, the cable nerve interpositioning technique is a convenient and well-accepted procedure for immediate restitution of the nerve.

18.
Food Microbiol ; 68: 61-70, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28800826

RESUMO

The main aim of this work was to evaluate, at pilot scale in an industrial environment, the effects of the biocontrol agent Lactococcus lactis CBM21 and thyme essential oil compared to chlorine, used in the washing step of fresh-cut lamb's lettuce, on the microbiota and its changes in relation to the time of storage. The modification of the microbial population was studied through pyrosequencing in addition to the traditional plate counts. In addition, the volatile molecule and sensory profiles were evaluated during the storage. The results showed no significant differences in terms of total aerobic mesophilic cell loads in relation to the washing solution adopted. However, the pyrosequencing data permitted to identify the genera and species able to dominate the spoilage associations over storage in relation to the treatment applied. Also, the analyses of the volatile molecule profiles of the samples during storage allowed the identification of specific molecules as markers of the spoilage for each different treatment. The sensory analyses after 3 and 5 days of storage showed the preference of the panelists for samples washed with the combination thyme EO and the biocontrol agent. These samples were preferred for attributes such as flavor, acceptability and overall quality. These results highlighted the effect of the innovative washing solutions on the quality of lettuce through the shift of microbiota towards genera and species with lower potential in decreasing the sensory properties of the product.


Assuntos
Bactérias/efeitos dos fármacos , Lactococcus lactis/fisiologia , Alface/microbiologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Thymus (Planta)/química , Verduras/microbiologia , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Biodiversidade , Contaminação de Alimentos/prevenção & controle , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/isolamento & purificação
19.
J Cardiovasc Med (Hagerstown) ; 18(8): 572-579, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28590305

RESUMO

BACKGROUND: Patients with diabetes mellitus and acute coronary syndrome (ACS) present an increased risk of adverse cardiovascular events. An Italian Consensus Document indicated 'three specific must' to obtain in this subgroup of patients: optimal oral antiplatelet therapy, early invasive approach and a tailored strategy of revascularization for unstable angina/non-ST-elevation-myocardial infarction (UA/NSTEMI); furthermore, glycemia at admission should be managed with dedicated protocols. AIM: To investigate if previous recommendations are followed, the present multicenter prospective observational registry was carried out in Lombardia during a 9-week period between March and May 2015. METHODS AND RESULTS: A total of 559 consecutive ACS patients (mean age 68.7 ±â€Š11.3 years, 35% ≥75 years, 50% STEMI), with 'known DM' (56%) or 'hyperglycemia', this last defined as blood glucose value ≥ 126 mg/dl at admission, were included in the registry at 29 hospitals with an on-site 24/7 catheterization laboratory. Patients with known diabetes mellitus received clopidogrel in 51% of the cases, whereas most patients with hyperglycemia (72%) received a new P2Y12 inhibitor: according to clinical presentation in case STEMI prasugrel/ticagrelor were more prescribed than clopidogrel (70 vs. 30%, P < 0.001); on the contrary, no significant difference was found in case of UA/NSTEMI (48 vs. 52%, P = 0.57).Overall, 96% of the patients underwent coronary angiography and 85% received a myocardial revascularization (with percutaneous coronary intervention in 92% of cases) that was however performed in fewer patients with known diabetes mellitus compared with hyperglycemia (79 vs. 90%, P = 0.001).Among UA/NSTEMI, 85% of patients received an initial invasive approach, less than 72 h in 80% of the cases (51% <24 h); no difference was reported comparing known diabetes mellitus to hyperglycemia. Despite similar SYNTAX score, patients with known diabetes mellitus had a higher rate of Heart Team discussion (29 vs. 12%, P = 0.03) and received a surgical revascularization in numerically more cases.Most investigators (85%) followed a local protocol for glycemia management at admission, but insulin was used in fewer than half of the cases; diabetes consulting was performed in 25% of the patients and mainly in case of known diabetes mellitus. CONCLUSION: Based on data of the present real world prospective registry, patients with ACS and known diabetes mellitus are treated with an early invasive approach in case of UA/NSTEMI and with a tailored revascularization strategy, but with clopidogrel in more cases; glycemia management is taken into account at admission.


Assuntos
Síndrome Coronariana Aguda/terapia , Diabetes Mellitus/epidemiologia , Hiperglicemia/epidemiologia , Revascularização Miocárdica , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/complicações , Adenosina/análogos & derivados , Adenosina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Angiografia Coronária , Gerenciamento Clínico , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/uso terapêutico , Estudos Prospectivos , Sistema de Registros , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
20.
G Ital Cardiol (Rome) ; 18(4): 305-312, 2017 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-28492570

RESUMO

The purpose of cardiopulmonary resuscitation after sudden cardiac arrest is to restore minimal blood flow to provide oxygen to the brain and other vital organs. Chest compressions and external defibrillation are the first line for circulatory support. Although early defibrillation is the main factor influencing survival, cardiopulmonary resuscitation must be characterized by high-quality external chest compressions. Unfortunately, the performance of manual chest compressions decreases during time and in hostile conditions. For these reasons, mechanical devices for chest compression are able to support rescuers during cardiopulmonary resuscitation. Commonly used mechanical chest compression devices in Europe include LUCAS and Autopulse. Routine utilization of mechanical chest compression devices cannot be recommended because randomized controlled trials, such as LINC and PARAMEDIC for LUCAS and CIRC for Autopulse, have not demonstrated their superiority compared with manual chest compressions. The aim of this review is to analyze recent data regarding utilization of mechanical chest compression devices, and to clarify advantages and limitations.


Assuntos
Reanimação Cardiopulmonar/instrumentação , Parada Cardíaca/terapia , Desenho de Equipamento , Hospitalização , Humanos , Parada Cardíaca Extra-Hospitalar/terapia
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