Abnormal anandamide metabolism in celiac disease Battista, Natalia; Di Sabatino, Antonio; Di Tommaso, Monia ...
The Journal of nutritional biochemistry,
10/2012, Letnik:
23, Številka:
10
Journal Article
Recenzirano
The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of ...the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase–polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic–tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic–tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic–tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.
The skeleton of a female adult found in archaeological excavations carried out in Siena (central Italy) and dated back to the modern age showed a severe skull malformation due to the premature ...bilateral closure of the coronal suture, which determined a deformed brachycephalic skull. This craniosynostosis was associated with other malformations, such as shallow orbits, hypertelorism, mandibular prognathism, and consequent malocclusion, but there was absence of anomalies in the remaining bones of the extremities. These features did not seem to be related to an isolated condition but to a more complex genetic syndrome, suggesting a possible case of Crouzon syndrome. Besides representing a rare finding in archaeological material, the present case provides the opportunity to observe in an adult subject lesions typical of this congenital disorder, which is at present surgically corrected in infantile age.
•Older adults who live alone become even more vulnerable after hospitalization.•Hospitalized older adults who live alone have a higher risk of non-home discharge.•In older adults, condition of living ...alone may prolong length of hospital stay.•Hospitalized older adults who live alone require a personalized discharge planning.
Explicit criteria for potentially inappropriate prescriptions in the elderly are recommended to avoid prescriptions of duplicate drug classes and to optimize monotherapy within a single drug class ...before a new agent is considered. Duplicate drug class prescription (or therapeutic duplicates) puts the patient at increased risk of adverse drug reactions with no additional therapeutic benefits. To our knowledge, the prevalence of elderly inpatients receiving therapeutic duplicates has never been studied.
Our objective was to assess the prevalence of therapeutic duplicates at admission, discharge, and 3-month follow-up of hospitalized elderly patients.
This cross-sectional prospective study was conducted in 97 Italian internal medicine and geriatric wards. Therapeutic duplicates were defined as at least two drugs of the same therapeutic class prescribed simultaneously to a patient. A patient's drug therapy at admission relates to prescriptions from general practitioners, whereas prescriptions at discharge are those from hospital internists or geriatricians.
The study sample comprised 5821 admitted and 4983 discharged patients. In all, 143 therapeutic duplicates were found at admission and 170 at discharge. The prevalence of patients exposed to at least one therapeutic duplicate rose significantly from hospital admission (2.5 %) to discharge (3.4 %; p = 0.0032). Psychotropic drugs and drugs for peptic ulcer or gastroesophageal reflux disease were the most frequently involved. A total of 86.8 % of patients discharged with at least one therapeutic duplicate were still receiving them at 3-month follow-up.
Hospitalization and drugs prescribed by internists and geriatricians are both factors associated with a small but definite increase in overall therapeutic duplicates in elderly patients admitted to internal medicine and geriatric wards. More attention should be paid to the indications for each drug prescribed, because therapeutic duplicates are not supported by evidence and increase both the risk of adverse drug reactions and costs. Identification of unnecessary therapeutic duplicates is essential for the optimization of polypharmacy.
Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole ...accounts for no more than 3%-5% of all breast cancers.
Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers.
It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.
Matrix metalloproteinases (MMPs) are a family of endopeptidases playing a key role in tissue remodelling in both physiological and pathological conditions. Since little information is available about ...their role in celiac disease (CD), our aims were to quantify their expression/activity and to investigate their relation to proinflammatory cytokines in this condition. Duodenal biopsies from untreated, treated celiac patients and controls were used to quantify the expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, MMP-14, their inhibitor TIMP-1, IFN-gamma and TNF-alpha by using real-time reverse transcription-polymerase chain reaction and the gelatin/casein/elastin activities by gel zymography, and to isolate lamina propria mononuclear cells (LPMCs). These cells and myofibroblasts isolated from jejunal specimens were incubated in the absence or presence of IFN-gamma and TNF-alpha. MMP-1 and MMP-12 mRNA levels were significantly increased in active CD compared to treated (P<0.01 and P<0.0005, respectively) and normal mucosa (P<0.01 and P<0.0005, respectively), and this was paralleled by an upregulation of caseinolytic and elastolytic activities. Furthermore, MMP-12 levels significantly (P<0.05) correlated with those of IFN-gamma and the degree of villous flattening. MMP-2 turned out to be significantly (P<0.05) reduced in untreated and treated celiacs compared to controls. In active CD, transcripts of TIMP-1 were higher than in treated and controls (P<0.005 and P<0.05, respectively), such as those of IFN-gamma (P<0.05), whereas TNF-alpha levels were suppressed (P=0.0001). In physiological condition, myofibroblasts represent the main source of MMP-2, whereas LPMCs produce almost all MMPs only after cytokine stimulation. Conversely, cells isolated from active patients constitutively express MMPs without any increase after cytokine stimulation, while those from treated patients are in a resting condition. In conclusion, our results show the presence of a peculiar MMP pattern in active CD strongly dominated by MMP-12, correlating either with IFN-gamma or the degree of mucosal damage.
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