Influence of HIV infection on vitamin status and requirements.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
G Shor-Posner
Publications and source records attributed to G Shor-Posner.
Czech and Slovak Federal Republic: not too late to slow HIV-1 spread.
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Czechoslovakia↗
Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.
Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.
Adult↗
Specific nutrient abnormalities in asymptomatic HIV-1 infection.
OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.
Adult↗
Vitamin B12 in early human immunodeficiency virus-1 infection.
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Adult↗
Self-selecting albino rats exhibit differential preferences for pure macronutrient diets: characterization of three subpopulations.
Analyses of natural feeding behavior in albino male Sprague-Dawley rats demonstrate that, when allowed to self-select from pure macronutrient diets (protein, carbohydrate and fat), these rats of the same genetic strain can be categorized into 3 subpopulations according to either their 24-h or their 12-h nocturnal patterns of nutrient intake. A majority of the animals (HC for high carbohydrate, 50% of the total population) consumed a diet rich in carbohydrate relative to protein or fat, while a smaller population of rats (HF, 30%) preferred the fat diet, and an even smaller population (HP, 20%) chose a high-protein diet. These 3 subpopulations, after a few weeks of maintenance on the diets, differed in their body weight, with the HF rats having a higher body weight than the HP animals, who tended to weigh more than the lightest HC rats. Whereas all subgroups exhibited a similar bimodal distribution of feeding during the nocturnal cycle, with peaks during the early and late dark periods, they were distinguishable on the basis of their nutrient consumption during specific phases of the dark cycle. This difference was most apparent in the early dark phase, when the 3 subgroups exhibited exaggerated preferences for the specific nutrient that was generally preferred over the 24-h cycle. This is in contrast to the middle dark phase, when diet preferences were attenuated or lost, and the late dark phase, when most rats were similar in showing an increased preference for protein and fat and a decreased preference for carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Association of vitamin B6 status with parameters of immune function in early HIV-1 infection.
Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function.
Acquired Immunodeficiency Syndrome↗
Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males.
Chemotherapeutic regimens frequently interact with and may influence nutritional factors. To determine the possible effects of zidovudine (ZDV) treatment on nutrient status, this study examined and compared the nutritional, immunological, and hematological status of asymptomatic, CDC stage III, HIV-1-seropositive males (n = 15) provided with ZDV (500-1,200 mg/day) and 22 nontreated, CD4-matched HIV-1-seropositive subjects. Prior to ZDV administration, hematological and plasma nutrient levels were similar in both groups. Following ZDV treatment, drug-treated subjects demonstrated alterations in hematological and nutritional parameters. A large proportion of the ZDV-treated participants exhibited decreased levels of zinc and copper along with a significant increase in red cell folate. The level of plasma zinc appeared to be particularly important in maintaining immune function in the ZDV-treated group. Whereas ZDV-treated subjects with adequate zinc levels displayed a significant increase in the response of peripheral blood lymphocytes to mitogens, this enhancement was not demonstrated in zinc-deficient, ZDV-treated participants or in untreated individuals whose lymphocyte response significantly declined over time, despite adeqaute zinc status. The findings of this study reveal a zidovudine-induced effect on nutritional parameters, indicating the importance of monitoring nutritional status with drug therapeutic regimens.
Adult↗
Nocturnal patterns of macronutrient intake in freely feeding and food-deprived rats.
Analyses of rats' feeding behavior at the start and the end of the nocturnal cycle have revealed dramatic alterations in macronutrient intake over time. At dark onset, rats displayed a preference for carbohydrate, with the first meal of the night consisting of approximately 60% of this nutrient. This carbohydrate intake was soon followed by a shift toward protein-predominant meals. Superimposed on this pattern of meal-to-meal shifts in nutrient selection appears to be an additional rhythm in which carbohydrate ingestion was favored at dark onset and protein and fat ingestion were favored during the late dark hours. Differential feeding patterns were also apparent following mild food deprivation. A 2-h period of deprivation at dark onset produced a strong compensatory feeding response, particularly of fat and carbohydrate. This pattern was not observed at the end of the dark, when little compensatory feeding was demonstrated. It is suggested that these feeding patterns may be related to the activity of certain hypothalamic neurotransmitters, e.g., norepinephrine and serotonin, known to be important in modulating temporal feeding patterns and nutrient intake.
Animals↗
Clonidine hyperphagia: neuroanatomic substrates and specific function.
Recent studies have indicated that the alpha 2-noradrenergic agonist clonidine (CLON), when peripherally and centrally administered, potentiates feeding in satiated rats in a manner similar to that observed following injection of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN). The present experiments examined the effects of CLON on meal patterns and macronutrient selection and compared these findings to earlier NE-stimulated feeding studies. Administration of CLON (25 nmoles), directly into the PVN (n = 5), similar to PVN injected NE, produced an increase in meal size (190%) and feeding duration (164%), with no change in meal frequency. Additional tests were conducted in rats with PVN electrolytic or 6-hydroxydopamine lesions. In Sham rats (n = 16) peripheral CLON (0.05 mg/kg), like NE, produced an increase in food intake and particularly potentiated carbohydrate ingestion. Discrete electrolytic lesions of the PVN (n = 5) abolished this CLON-induced feeding and carbohydrate preference, suggesting that the PVN may be a primary site for CLON-stimulated hyperphagia. Neurotoxin lesions of the PVN (n = 17), which reduced PVN NE levels by 75%, failed to alter peripheral CLON-induced feeding. This and other evidence indicates that this agonist may be acting via postsynaptic alpha 2 receptors in the PVN to potentiate carbohydrate intake, rather than via presynaptic release of NE from nerve endings in the PVN.
Animals↗
Hypothalamic serotonin: pharmacological, biochemical, and behavioral analyses of its feeding-suppressive action.
Studies of the neuropharmacology of eating behavior demonstrate that monoaminergic neurotransmitters in the brain have an active and important role in the control of food ingestion, in animals and also possibly in humans. The anatomical focus of the animal studies has been the hypothalamus, which appears to play a key role in this process. This structure receives and integrates input from metabolic, hormonal, neurogenic, thermal, and cortical factors, which reflect the nutritional status of the organism, and then it translates this information into signals for inducing appropriate adjustments in food consumption. While this review focuses on the indoleamine, serotonin, with respect to its effects after peripheral and central administration, attention is also given to the catecholamines, which are believed to interact with serotonin in the complex process of controlling eating patterns and appetite for specific macronutrients.
Animals↗
Medial hypothalamic serotonin in the control of eating behavior.
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Animals↗
Destruction of noradrenergic innervation to the paraventricular nucleus: deficits in food intake, macronutrient selection, and compensatory eating after food deprivation.
Norepinephrine (NE) injected into the paraventricular nucleus (PVN) has a stimulatory effect on feeding behavior and is found to selectively enhance preference for carbohydrate in the rat. The present experiments were conducted to assess the impact of chronic depletion of NE within the PVN on food intake and appetite regulation. The catecholamine (CA) neurotoxin, 6-hydroxydopamine (6-OHDA), when administered into the PVN, produced a significant depletion of PVN NE in association with a variety of behavioral changes. The immediate consequence of the neurotoxin lesion was a dramatic increase in 24-hr food intake, attributed predominantly to a preferential increase in carbohydrate and fat consumption. The long-term effects related to CA depletion were a deficit in daily food consumption, particularly of carbohydrate (-42%). Although animals with diminished PVN NE maintained a normal diurnal feeding pattern, they failed to exhibit the increased ingestion of an energy-rich carbohydrate diet which rats normally show during the dark period of the diurnal cycle. Rats injected with 6-OHDA directly into the PVN exhibited a normal response to glucoprivic challenge, but demonstrated a deficit in their ability to produce compensatory feeding, particularly of carbohydrate and fat, in response to food deprivation. These findings suggest a specific function for PVN noradrenergic mechanisms in normal energy repletion when body energy stores are reduced.
Adaptation, Physiological↗
Morphine-stimulated feeding: analysis of macronutrient selection and paraventricular nucleus lesions.
The hypothalamic paraventricular nucleus (PVN) has been found to be sensitive to the feeding stimulatory effects of opiates. The present experiments investigated the effect of systemic morphine (2 mg/kg) on macronutrient selection in freely-feeding and food-restricted rats and assessed the impact of PVN electrolytic and 6-hydroxydopamine lesions on the rats' ability to respond to peripheral morphine injection. In satiated rats, maintained ad lib on pure macronutrient diets, morphine increased food intake. This effect was associated with a preferential increase in protein ingestion; carbohydrate consumption, compared with fat and protein intake, was least affected. In food-restricted rats, permitted to eat for 6 hr, morphine instead produced a particular preference for fat, with no significant enhancement of total calorie intake. While PVN 6-hydroxydopamine lesions, which depleted PVN catecholamine levels by 70%, failed to alter morphine-stimulated feeding, electrolytic lesions of the PVN significantly attenuated this response, particularly protein and fat ingestion. This suggests that opiate-induced feeding may, in part, be mediated through the PVN, which is known to have an important function in the control of food ingestion.
Animals↗
Hypothalamic serotonin in the control of meal patterns and macronutrient selection.
Serotonin (5-HT) is believed to have an inhibitory influence over feeding behavior. The present experiments were designed to investigate the effects of hypothalamic 5-HT on spontaneously motivated feeding and appetite regulation. Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer. Following PVN 5-HT or NORFENF injection, animals exhibited a marked suppression in food intake, associated with a decrease in meal size, duration and eating rate, and no change in the frequency of meals consumed. This suggests that brain 5-HT may influence primarily the induction of satiety rather than the suppression of hunger. The effect of drugs presumed to affect brain 5-HT transmission on diet selection was also investigated in groups of rats injected centrally with 5-HT or NORFENF or peripherally with either fenfluramine, quipazine or cyproheptadine. In a series of 2-diet tests, rats centrally injected with 5-HT or NORFENF exhibited a selective suppression of the carbohydrate-rich diets. In animals provided with three pure macronutrient diets, protein, carbohydrate, and fat, systemic administration of serotonergic agents had its greatest impact on fat and carbohydrate ingestion, as compared to protein consumption. These findings support a role for hypothalamic 5-HT in modulating meal patterns and appetite for particular macronutrients.
Animals↗
Amphetamine: effects on meal patterns and macronutrient selection.
Catecholaminergic systems, specifically in the region of the lateral perifornical hypothalamus (PFH), have been linked to the inhibition of feeding behavior. The present studies examined the effects of d-amphetamine (AMPH), which is believed to act through the release of endogenous catecholamines (CAs), on spontaneous feeding and appetite regulation in rats. Injection of AMPH directly into the PFH caused a marked suppression of food intake; changes in computer-monitored meal patterns were characterized by an increase in the latency to meal onset and a consequent reduction in meal size and duration. This suggests that hypothalamic AMPH administration may influence primarily the initiation, rather than the termination, of feeding. In other experiments, chronic infusion of AMPH directly into the PFH was shown to suppress 24 hr food intake and body weight gain, indicating the effectiveness of lateral hypothalamic CA stimulation in overriding normal long-term patterns of feeding. The effect of hypothalamic CA stimulation on macronutrient selection was also investigated in groups of rats injected either centrally or peripherally with AMPH, or centrally with the CA agonists, dopamine and epinephrine. Each of these manipulations caused a strong inhibition of protein intake with no effect on carbohydrate, and only a mild suppression of fat ingestion after peripheral AMPH. These selective effects of AMPH on feeding patterns and diet choice, provide support for a role of CA innervation to the lateral hypothalamus in the modulation of natural feeding behavior and macronutrient selection.
Animals↗
Brain serotonin and eating behavior.
Studies indicate that hypothalamic monoamine systems involved in the control of food intake have specific effects on temporal feeding patterns and on appetite for specific macronutrients. Based on the evidence obtained in rats, it is proposed that serotonin acts, in part, through a satiety mechanism of the medial hypothalamus, to reduce ingestion of carbohydrate while sparing protein intake. In controlling the ratio of carbohydrate to protein intake, this serotonergic system, which is responsive to the anorectic agent fenfluramine, is believed to function in direct opposition to the alpha 2-noradrenergic system of the paraventricular nucleus, which inhibits satiety for carbohydrate and thereby potentiates the size of carbohydrate meals. This serotonergic system may also indirectly oppose the catecholaminergic systems of the lateral hypothalamus, which mediate amphetamine anorexia and which inhibit a hunger-stimulating system for protein intake, thereby delaying the initiation of protein meals. Examination of the rats' normal eating patterns, in conjunction with particular biochemical analyses, has indicated specific points in the circadian eating cycle where these hypothalamic monoamine systems, in association with changes in circulating hormones and nutrients, may be physiologically activated.
Amphetamine↗
Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions.
Noradrenergic mechanisms of the hypothalamic paraventricular nucleus (PVN) have been shown to play an important role in the stimulation of feeding To determine the influence of this nucleus in monitoring and controlling responses to physiological and pharmacological challenges, PVN electrolytic lesion rats were tested for their behavioral responsiveness to agents known to affect the alpha-2 noradrenergic system as well as release of corticosterone, and to short- and long-term periods of food deprivation. Discrete lesions of the PVN produced enhanced feeding, particularly of carbohydrate, in freely-feeding rats maintained on a macronutrient self-selection paradigm. Lesion rats demonstrated a behavioral deficit in food intake regulation (a decrease in carbohydrate ingestion) in response to 5-hr and 24-hr fasts, showed a disturbance in circadian feeding, and exhibited a dramatic decrease in circulating corticosterone. However, feeding in response to 2-deoxy-D-glucose and insulin remained intact, suggesting that noradrenergic receptors within the PVN are not involved in the mediation of glucoprivic-induced feeding.
Animals↗