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1.  FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer’s disease 
Objective
Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer’s disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD.
Methods
In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion.
Results
A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510–70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups.
Conclusion
FOXO1 may influence the clinical response to AChEIs in AD patients.
doi:10.2147/CIA.S64758
PMCID: PMC4211854  PMID: 25364236
forkhead box O1; acetylcholinesterase inhibitors; response to treatment
2.  Irritable bowel syndrome: A disease still searching for pathogenesis, diagnosis and therapy 
Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.
doi:10.3748/wjg.v20.i27.8807
PMCID: PMC4112881  PMID: 25083055
Irritable bowel syndrome; Pathogenesis; Diagnosis; Therapy
3.  Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients 
Age  2010;33(3):409-419.
The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR = 1.54, 95% CI 1.04–2.29). This association was significant in men (OR = 2.01, 95% CI 1.07–3.78), but not in women (OR = 1.36, 95% CI 0.82–2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.
doi:10.1007/s11357-010-9192-2
PMCID: PMC3168594  PMID: 21076879
Angiotensin-converting enzyme; Disability; Aging; Hospitalized patients

Results 1-3 (3)