Alcohol consumption and mortality in aging or aged Finnish men

The association between alcohol consumption and 10-year mortality by death cause was studied in 1112 men aged 55-74 years and living either in eastern or south-western Finland. After adjustment for age, blood pressure, smoking, serum cholesterol, and other variables, the relative odds ratio of 10-year total mortality associated with consuming 1-273 g of absolute alcohol per month was 0.9 (95% confidence interval of 0.6-1.2) and with consuming more than 273 g per month due to violence was small, 15, but relative odds of violent death associated with consuming 1-273 and 274 or more grams of alcohol per month were 3.4 and 16.2, respectively (95% confidence intervals of 0.4-31.9 and 1.9-141.2).     

Functional expressions of the aging brain

In the conventional view, aging of the brain is associated with atrophy vascular abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging is associated with slowing of processing and memory loss. However, many studies of aging do not examine the cases to exclude demented people. The nutrition and memory in the homebound elderly study (NAME) excluded cases clinically diagnosed as having dementia. Cortical atrophy based on MRI ratings was significantly correlated with vascular disease, white matter hyperintensities, processing speed, and memory but not hippocampus and amygdala volume. Renal function and homocysteine were also associated with cortical atrophy but not with the cognitive variables. In conclusion, brain atrophy of aging in the absence of dementia is related to vascular disease but not hippocampal atrophy. Studies of nutritional interventions should consider using MRI atrophy rather than cognition as outcome.     

Nicotinic receptor subtypes in human brain related to aging and dementia.

Neuronal nicotinic receptors are attracting increasing interest, beyond their role in relation to tobacco use, in the areas of human brain aging and disorders associated with dementia. Of the different receptor subtypes in the mammalian brain, many decline with normal aging in several different areas, including particularly cerebral cortex and hippocampus. There are further select subtype changes in the two most common forms of dementia in the elderly: Alzheimer's disease and dementia with Lewy bodies. The alpha4 subunit is most extensively reduced in the cortex in Alzheimer's disease, reflected in the loss of the high affinity binding site. There are also reductions in the low affinity binding site (alpha-bungarotoxin binding) in the thalamus in both disorders, which are likely to reflect the loss of the homomeric (most commonly alpha7) receptor subtype. Correlations exist between some of these receptor abnormalities and clinical and pathological features of the diseases. Targeting such receptors is a current therapeutic objective.     

Impact of lead toxicity on brain metabolisms of nucleic acid and catecholamine in protein malnourished rats.

The brain biochemistry in terms of certain key substances of brain were studied in 18% protein and 6% protein-fed rats following lead ingestion at a level of 1% in the diet. Lead ingestion diminished the protein and increased the RNA content of brain, and, consequently reduced the protein/RNA ratio. The RNA/DNA ratio in brain was elevated in lead toxicity, while the protein/DNA ratio remained unaltered. The RNase and DNase activities of brain were decreased. Lead treatment diminished the glutathione (GSH) level of blood but the GSH level of brain was not altered significantly by the lead treatment. The plasma protein level was also diminished after lead treatment. The effects of lead on some of these parameters were found to be more pronounced in rats receiving the 6% protein diet. The serotonin (5-HT) level of brain was reduced, while the norepinephrine (NE) and dopamine (DA) levels of brain were elevated following lead treatment. The monoamine oxidase (MAO) and tryptophan hydroxylase (TPH) activities and 5-hydroxy-indole acetic acid (5-HIAA) content of brain were elevated in lead-ingested rats. The effects of lead on these parameters were found to be potentiated when the rats were fed on a 6% protein diet. These studies suggest that lead at the present dose affects brain biochemistry in terms of both nucleic acids and amine metabolism, and protein deficiency potentiates some of these lead-induced changes.     

Alcohol metabolism and fetal hypoplasia in chick brain

Chick embryos given a single dose of ethanol (1.0 g/kg) at the start of incubation (day 0) had widely differing levels of blood alcohol when sacrificed on day 7 and the blood alcohol levels were inversely correlated with whole body and brain weight. Clearance of the alcohol by the embryos was inhibited by simultaneous treatment with 4-methyl pyrazole and this treatment potentiated the brain growth inhibition due to ethanol. Treatment with indomethacin lowered blood alcohol levels on day 7 and protected against the growth inhibition. These data suggest that early chick embryos have varying amounts of alcohol dehydrogenase-like metabolic activity and that higher levels of this activity protect against alcohol-induced brain growth inhibition in this model. If similar variations in the ability to metabolize alcohol exist in human fetuses, it may represent a mechanism by which comparable maternal doses of alcohol produce widely varying fetal effects.     

Alcohol inhibition of suckling-induced prolactin release in lactating rats: threshold evaluation

Prolactin release in response to suckling was examined in primiparous lactating rats two hours after alcohol administration. Litters were adjusted to eight pups on lactation day 2 and dams were implanted with an atrial catheter on day 6. On day 10, pups were separated from the mother at 0800 h. An extension was attached to the catheter at 1100 h. Following removal of a baseline blood sample an hour later, rats were infused with alcohol doses of 0, 0.5, 1.0, 2.0 or 2.5 g/kg body weight. Two hours later, pups were returned to dams. Subsequent blood samples were obtained 10, 30, 60, 120 and 180 min after the onset of suckling. Following 10 min of suckling, plasma prolactin for groups of rats infused with alcohol at 2.0 and 2.5 g/kg body weight were lower than control, 0.5 and 1.0 g/kg groups. The blood alcohol level (BAL) for the 2.0 g/kg group was 94 +/- 8 mg% and for the 2.5 g/kg group was 162 +/- 4 mg%. After 30 min, the BAL for the 2.5 g/kg group was 134 +/- 5 mg% and plasma prolactin was suppressed in this group compared to control, 0.5 and 1.0 g/kg groups. The BAL for the 2.0 g/kg group after 30 min of suckling was 74 +/- 9 mg% but prolactin was not significantly lower than controls. We conclude that in rats, alcohol inhibition of suckling-induced prolactin release is directly correlated to the BAL. The threshold BAL which effectively inhibits this prolactin release is lower than the human legal intoxication level.     

Alcohol consumption by aging adults in the United States: health benefits and detriments

The most rapidly growing segment of the US population is that of older adults (≥65 years). Trends of aging adults (those aged ≥50 years) show that fewer women than men consume alcohol, women consume less alcohol than men, and total alcohol intake decreases after retirement. A U- or J-shaped relationship between alcohol intake and mortality exists among middle-aged (age 45 to 65 years) and older adults. Thus, alcohol can be considered either a tonic or a toxin in dose-dependent fashion. Active areas of research regarding the possible benefits of moderate alcohol consumption among aging individuals include oxidative stress, dementia, psychosocial functioning, dietary contributions, and disease prevention. Yet, due to the rising absolute number of older adults, there may be a silent epidemic of alcohol abuse in this group. Dietary effects of moderate and excessive alcohol consumption are reviewed along with mechanisms by which alcohol or phytochemicals modify physiology, mortality, and disease burden. Alcohol pharmacokinetics is considered alongside age-related sensitivities to alcohol, drug interactions, and disease-related physiological changes. International guidelines for alcohol consumption are reviewed and reveal that many nations lack guidelines specific to older adults. A review of national guidelines for alcohol consumption specific to older adults (eg, those offered by the National Institute on Alcohol Abuse) suggests that they may be too restrictive, given the current literature. There is need for greater quantification and qualification of per capita consumption, consumption patterns (quantity, frequency, and stratified combinations), and types of alcohol consumed by older adults in the United States.     

Interaction of aging and intermittent ethanol exposure on brain cytochrome c oxidase activity levels.

The effects of chronic, intermittent ethanol exposure on brain cytochrome c oxidase (CO) activity levels were studied in young (3- to 4-month-old) and aged (29- to 30-month-old) male Wistar rats. The rats were given highly intoxicating doses of ethanol three times a day by intragastric intubation for four successive days, followed by a 3-day ethanol-withdrawal period. This 4-day ethanol-exposure with 3-day ethanol-withdrawal cycle was repeated five times to simulate the binge drinking of human alcoholics. The histochemical demonstration of CO showed a markedly decreased activity level in the medial prefrontal cortex (especially layer V pyramids and neuropil) of the ethanol-exposed rats of both age groups compared with findings for the respective controls. In the cerebellar vermis, CO activity level was decreased in the Purkinje neurons of the aged ethanol-exposed rats and in the granule cells of both young and aged ethanol-exposed rats. The CO activity level in the locus coeruleus was decreased in both young and old ethanol-exposed rats, but the decrease was more pronounced in the young ethanol-exposed group. Aging per se did not markedly change CO histochemical findings in either prefrontal or cerebellar cortex, but CO activity levels were increased in the locus coeruleus. In summary, results of the current study support our conclusion that CO activity levels were decreased in the cerebral and cerebellar cortices as well as in the locus coeruleus-CNS regions known to be negatively affected by chronic ethanol exposure. Defective energy metabolism due to decreased CO activity levels might compromise neuronal energy stores and thereby contribute to ethanol-induced brain dysfunction and irreversible CNS degeneration.     

Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain

Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline.     

Effects of postnatal undernutrition on the catecholamine and serotonin contents of suckling rat brain

The effect of postnatal undernutrition on the catecholamine and serotonin contents of various parts of the brain of suckling rats was examined. Undernourishment was induced by increasing the litter size to 18 pups from day 1 to 21 after birth. In control pups, the total amounts of norepinephrine and dopamine in the whole brain increased greatly during the suckling period (norepinephrine: 17.7 ng at birth, 154 ng on day 10, and 420 ng on day 21; dopamine: 12.6 ng at birth, 269 ng on day 10, and 1,022 ng on day 21). Similar, but less marked increases in the norepinephrine and dopamine contents of the brain were observed in malnourished pups. The norepinephrine contents of the forebrain, cerebellum, and brain stem of malnourished pups were comparable with those of normal pups on day 10 but the contents of the cerebellum and brain stem were significantly less than those of normal pups on day 21. Postnatal malnutrition also led to a significant decrease in the dopamine content of the forebrain. In contrast, the serotonin content of the brain of undernourished pups was significantly higher than that of controls. The control pups at the end of suckling period were significantly higher than those of undernourished pups (forebrain: 18.3 pmol in controls and 11.5 pmol in malnourished pups; brain stem: 12.3 pmol in controls and 9.8 pmol in malnourished pups). The tyrosine hydroxylase activity (pmol/g) correlated more closely with the norepinephrine content than with the dopamine or norepinephrine plus dopamine content. The tyrosine and phenylalanine contents of the brain were similar in the two groups. It is concluded from these findings that the catecholamine content of the brain is regulated by the enzyme activity rather than the levels of precursor amino acids.     

Effects of prenatal styrene exposure on postnatal development and brain serotonin and catecholamine levels in rats

Maternal reproductive effects in Wistar rats exposed to 0, 50, or 300 ppm styrene for 6 h/day during gestational days 6 to 20 were evaluated. Their offspring were observed postnatally for neurochemical changes, growth, and physical landmarks of development. Mothers exposed to styrene were compared with pair-fed and ad-lib-fed controls in order to adjust nutrient conditions. Prolongation of the gestational period, food intake, and the number of neonatal deaths or stillbirths in 300-ppm-exposed dams showed evidence of styrene-related effects. Other reproductive parameters, such as litter size, birth weight, and sex ratio, were found to exhibit no effects within the variation range studied. A neurochemical effect was observed in that the 5-HT and HVA concentrations in cerebrum were significantly decreased. Incisor eruption (mandible), eye opening, and the air-righting reflex were delayed in rat pups born to dams receiving 300 ppm styrene exposure compared with the pair-fed and ad lib control groups. Pups born to dams exposed to 50 ppm styrene also had a significantly delayed air-righting reflex compared with ad lib controls. These results suggest that the offspring were susceptible to the effects of styrene on a few developmental landmarks even when nutritional effects were controlled.