Age, homocysteine, and oxidative stress: relation to hypertension and type 2 diabetes mellitus.

OBJECTIVES: Hyperhomocysteinemia and oxidative stress are independent risk factors for cardiovascular events, which occur more frequently in old age. We evaluated these parameters in relation to age and the presence of hypertension and type 2 diabetes mellitus. METHODS: Two hundred eighty-two subjects (female/male: 142/140; 141 were >65 years and 141 were <65 years; mean age 73.9 +/- 6.6 years and 52.5 +/- 8.2 years, respectively) were randomly recruited from those attending our institution. Blood pressure, anthropometric parameters, oxidative stress parameters (reactive oxygen species [ROS] and malondialdehyde [MDA]), and homocysteine levels were evaluated in participants. RESULTS: Homocysteine (2.9 +/- 0.06 vs. 2.3 +/- 0.03 micromol/L, p < 0.001) and oxidative stress (ROS: 10.8 +/- 0.3 vs. 8.1 +/- 0.3 mmol/L, p < 0.001; MDA: 1.62 +/- 0.05 vs. 1.21 +/- 0.05 nmol/mL, p < 0.001) were significantly higher in older vs. younger subjects without hypertension or diabetes. However, homocysteine and MDA were not significantly different in older vs. younger hypertensive subjects (homocysteine: 3.0 +/- 0.03 vs. 2.9 +/- 0.04 micromol/L, p = NS; MDA: 1.7 +/- 0.07 vs. 1.4 +/- 0.06 nmol/mL, p = NS) and in older vs. younger diabetic hypertensive subjects (homocysteine: 3.02 +/- 0.05 vs. 2.9 +/- 0.05 micromol/L, p = NS; ROS: 10.7 +/- 0.7 vs. 9.7 +/- 0.8 mmol/L, p = NS; MDA: 1.6 +/- 0.10 vs. 1.5 +/- 0.12 nmol/mL, p = NS). CONCLUSIONS: Aging is accompanied by elevated homocysteine and oxidative stress levels similar to those observed in younger subjects with hypertension or diabetes mellitus, independent of age. Hence, these conditions appear to accelerate the age-dependent increase in homocysteine and oxidative stress.

Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD).

Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimer's disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n=100, mean age 78.4±4.3 years) initiated treatment with donepezil, 5mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the training program, and after 2 months of follow-up. There was a significant improvement in mini-mental state examination (MMSE) score (p<0.001) and the AD assessment scale-cognitive (ADAS-Cog) subscale (p<0.001), without changes in impaired activity of daily living (ADL) and instrumental ADL (IADL) after intensive ROT training in Group A. MMSE was maintained after 2 months in-home ROT continuation. There were no significant changes in MMSE in drug-only treated patients (Group B) after 3 weeks, with a non-significant tendency to improvement in ADAS-Cog. Our results suggest benefit of an intensive ROT program in dementia patients receiving donepezil that seems to be maintained as far as ROT is continued by the caregiver.

Azithromycin in an older woman with diabetic gastroparesis.

Diabetic neuropathy is a common chronic complication of diabetes and cause of significant morbidity and mortality, because it may involve the autonomous and peripheral nervous systems. Autonomic diabetic neuropathy is a challenging chronic complication of long-standing diabetes manifested with hypotension, syncope, gastroparesis, diarrhea, constipation, bladder dysfunction, sexual dysfunction, cardiac arrest, and/or sudden death. We present a case of diabetic gastroparesis in an older woman. The patient was an 83-year-old woman with a 40-year history of type 2 diabetes who was admitted with hypoglycemia, malnutrition, persistent vomiting, and obstinate constipation. After several unsuccessful attempts with different therapies, we administered intravenous azithromycin (500 mg/day). After 3 days of treatment, vomiting was resolved and the patient evacuated normal feces, with notable improvement in the general conditions and metabolic control. Because diabetic gastroparesis frequently is difficult to manage clinically and there are few beneficial therapeutic choices available at present, the macrolide antibiotic azithromycin, which has strong prokinetic properties, may be a useful option in the treatment of this complex condition.

Blood pressure and cardiovascular risk profiles of Africans who migrate to a Western country.

OBJECTIVES: Africans who live in Western countries have a higher prevalence of hypertension and other cardiovascular risk factors than do age-matched Africans who live in Africa. We conducted a community survey to evaluate cardiovascular risk in Africans who recently migrated to Italy. METHODS: Participants (N=83) from sub-Saharan Africa were recruited from an outpatient clinic for immigrants. Information on immigration date, family history of cardiovascular disease, physical activity, and smoking was obtained for all participants. Anthropometric parameters, blood pressure measurements, and laboratory analyses--including lipid profiles, plasma glucose, renal function, and serum and urinary electrolytes--were performed. RESULTS: Although participants who had recently arrived in Italy had a low cardiovascular risk, the correlations were significant between the length of time in Italy and body weight (r=.47, P<.001), body mass index (r=.59, P<.0001), waist circumference (r=.54, P<.0001), total cholesterol (r=.41, P<.001), low-density lipoprotein cholesterol (r=.46, P<.0001), systolic blood pressure (r=.31, P<.01), and diastolic blood pressure (r=.23, P<.05). The rise in systolic and diastolic blood pressure was positively correlated with body weight, body mass index, and waist circumference (P<.05 for all) and inversely correlated with 24-hour urinary potassium (systolic blood pressure, r=-.35, P<.01; diastolic blood pressure, r=-.42, P<.0001). CONCLUSIONS: The length of residence in Italy is associated with progressive modifications in cardiovascular risk even in a relatively short period of time. The inverse correlation between blood pressure and urinary potassium may reflect dietary changes, with a possible reduction in fruit and vegetable consumption compared with their original diet.

Cardiovascular risk factors in centenarians.

Several studies have shown that centenarians have better cardiovascular risk profiles compared to younger old people. Some reports have revealed that cardiovascular diseases (i.e. hypertension, diabetes, angina and/or myocardial infarction) are less common in centenarians respect to 70 and 80 years old persons. In order to explain this evidence, there is a growing number of hypothesis that consider a combination of genetic factors and lifestyle aspects to elucidate the exceptional longevity of centenarians, able to overcome the most frequent mortality cause, which is a cardiovascular event. It has been suggested that a role on this better cardiovascular risk profile may be played by the increasing use of pharmacologic treatments in the elderly population (specially for hypertension and dyslipidemia), but the contribution of drug treatments to promote extreme longevity is not confirmed. Furthermore, centenarians in general have needed fewer drugs at younger ages due to a healthy lifestyle. The importance of the genetic contribution is demonstrated by the inheritance of low-risk cardiovascular profiles in centenarian offspring and lower prevalence of cardiovascular diseases in this population as compared with their spouses or with age-matched subjects without centenarian parents. Another advantage in centenarians' offspring seems to be a delay in the onset for cardiovascular diseases, respect to age- and sex-matched controls. Cardiovascular risk factors mirror the factors that contribute to longevity. Hence, it is not surprising that these risk factors are less prevalent in centenarians when compared to younger old individuals.

[Current therapeutic approach in patients with Alzheimer disease]. / Attuale approccio terapeutico ai pazienti con malattia di Alzheimer.

Even if a complete recovery is not an available outcome for Alzheimer disease, it is possibile to improve the clinical symptoms (selfsufficiency, cognitive impairment and behavioral disturbances) with pharmacological and non-pharmacological therapies. The treatment of the patient with dementia is a complex one, that cannot rely only on the use of drugs but needs of a global approach that take into account all the different aspect of the disease. The most used drugs are the cholinesterase inhibitors that have been shown to stabilize or slow down cognitive and functional decline and retard institutionalization, but new treatments are on the way. Extremely important is a strong alliance with the family. Non pharmacological cognitive rehabilitation techniques are also useful in potentiating residual cognitive functions in the patient and in supporting the family and the caregivers.

Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X.

Magnesium (Mg) is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular Mg concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In vitro and in vivo studies have demonstrated that insulin may modulate the shift of Mg from extracellular to intracellular space. Intracellular Mg concentration has also been shown to be effective in modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli. A poor intracellular Mg concentration, as found in noninsulin-dependent diabetes mellitus (NIDDM) and in hypertensive patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in noninsulin-dependent diabetic and hypertensive patients. By contrast, in NIDDM patients daily Mg administration, restoring a more appropriate intracellular Mg concentration, contributes to improve insulin-mediated glucose uptake. The benefits deriving- from daily Mg supplementation in NIDDM patients are further supported by epidemiological studies showing that high daily Mg intake are predictive of a lower incidence of NIDDM. In conclusion, a growing body of studies suggest that intracellular Mg may play a key role in modulating insulin-mediated glucose uptake and vascular tone. We further suggest that a reduced intracellular Mg concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension.