Tricyclic structures in medicinal chemistry: an overview of their recent uses in non-CNS pathologies.

Tricyclic compounds are sometimes considered as synonima of drugs healing central nervous system pathologies, although there are some well known examples of tricyclic derivatives marketed for different indications, such as antihistamines, antivirals and antiulceratives. Following the insertion of tricyclic structures in the "privileged structures" pool, several compounds bearing a central 7-membered ring and two aryl rings at its sides have been reported, and some of them have been progressed to advanced clinical trials. An overview of tricyclic derivatives reported in the literature since 1995, that are investigated for indications not directly related to central nervous system affections, shows the potential of these structures in a broad range of therapeutical indications, going from antiviral and anticancer compounds to the therapy of cardiovascular diseases. Very recent examples confirm the usefulness of tricyclic structures for the modern medicinal chemists.

Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study.

Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.

Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.

In a family with autopsy-confirmed Alzheimer disease, the authors found a mutation in the presenilin 2 (PS2) gene (PSEN2) that predicts a methionine-to-isoleucine change at PS2 residue 239 (M239I), at which a change to valine was known in another family. Phenotypic expression of M239I was highly variable, with disease onset between age 44 and 58 years, and two nonaffected mutation carriers at age 58 and 68 years. The data showed no influence of APOE but were compatible with other possible genetic modifiers of the phenotype or penetrance of M239I.

Cognition and the perception of physical symptoms in the community-dwelling elderly.

Elderly people frequently complain of somatic (physical) symptoms that prompt them to seek medical intervention. The aim of this study was to evaluate the effect of cognitive impairment on somatic symptom complaints by the elderly. Symptoms (spontaneously reported and reported after explicit inquiry) pertaining to 15 organ systems were assessed in a random sample of 462 community-dwelling individuals over the age of 75 years. The symptoms increased with decreasing cognitive performance with no, very mild, and mild cognitive impairments as indicated on the Mini-Mental State Examination. The trend of increasing reports of symptom with decreasing cognitive performance was significant (p = .0001); the association remained significant after controlling for potential confounders in multivariate analysis (p < .05). The authors, who found that mild cognitive impairment was associated with perception of poorer body functioning, suggest that the clinical interpretation of somatic symptoms in the elderly should take cognitive impairment into account.

Echocardiographic vs hemodynamic monitoring during isometric exercise in patients with coronary artery disease.

BACKGROUND: Isometric exercise is able to induce myocardial asynergies in patients with coronary artery disease as demonstrated by noninvasive monitoring performed during stimulation. AIMS OF THE STUDY: In the present study, a combined echocardiographic and hemodynamic monitoring of left ventricular contractility has been conducted in order to verify, with invasive and noninvasive techniques, the ability of isometric exercise in inducing transient myocardial ischemic phenomena. METHODS: The study population was composed of 20 patients with angiographic evidence of significant coronary stenosis (> or = 50%), and 10 subjects with normal coronary angiograms. All 30 subjects admitted to the study underwent an isometric exercise stress during echocardiographic and hemodynamic monitoring of left ventricular contractility. RESULTS: Nine out of 20 patients with coronary disease showed regional asynergy during the test (Group I). The remaining 11 patients showed normal myocardial contractility (Group II). None of the 10 control subjects showed mechanical signs of ischemia during the test. Left ventricular end diastolic pressure significantly increased in both Group I (10 +/- 2 to 24 +/- 4 mmHg) and Group II (12 +/- 3 to 26 +/- 3 mmHg) (p < 0.01) while it remained unchanged in the control group (9 +/- 2 to 13 +/- 2 mmHg; p = NS); dp/dt increase (% basal) was significantly higher in the control group (45 +/- 6%) than in either Group I (25 +/- 3%) or Group II (26 +/- 3%) (p < 0.01). CONCLUSIONS: Isometric exercise was able to induce left ventricular asynergies due to regional myocardial ischemia. Hemodynamic contractility monitoring easily distinguished the control subjects from the patients with coronary disease but was not able to discriminate patients with handgrip-induced regional asynergy. Thus, the echocardiographic technique offers more detailed information about regional myocardial function than do the common hemodynamic contractility indexes.

Role of metabolic therapy in cardiovascular disease.

The pathophysiological basis for the use of metabolic therapy in the treatment of heart failure is analyzed. Bioenergetical processes related to ATP bioavailability play a central role in regulating myocardial contractility at rest and on effort. Furthermore, a significant correlation has been demonstrated in diseased heart between ATP content, revealed at endomyocardial biopsy, and systolic and diastolic left ventricular indexes evaluated with invasive and noninvasive methods. Several international investigations demonstrate the beneficial effects of ubiquinone (coenzyme Q10) in the treatment of heart failure. Here the results of a study are reported that was conducted on patients with heart failure treated with ubiquinone. After 7 months of oral drug administration (100 mg/day), a significant improvement was observed in echocardiographic indexes of systolic function, cardiothoracic ratio, and clinical signs and symptoms of congestive heart failure. In conclusion, the introduction of metabolic drugs, such as ubiquinone, in the treatment of heart failure opens new horizons in the therapeutic approach to an ailment that entails substantial human and social costs.