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J E Morley

Publications and source records attributed to J E Morley.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice.

Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS ) in vitro and in vivo. For in vitro analysis, mouse liver extracts were used. For the in vivo study, (ob/ob) and their control litter mates (ob/c) mice were injected with specified amounts of metformin and the expression of NOS in the adipose tissue and hypothalamus was measured by Western blotting. Results show that metformin exhibited a biphasic effect on NOS activity in vitro. Expression of metformin was differentially altered in the hypothalamus and adipose tissues of the normal and ob/ob animals that were treated with metformin. Further, a significant decrease in food intake occurred in the (ob/ob) mice that received metformin. This decrease in food intake was not accompanied by changes in serum glucose. At inhibitory concentrations, hypothalamic NOS expression changes differentially in normal and ob/ob mice. In normal mice, metformin stimulated NOS expression, while in ob/ob mice there was an inhibition. NOS expression increased in brown adipose tissue of metformin treated control mice, while no such increase was observed in ob/ob mice. No effect of metformin was observed in white adipose tissue of control or obese mice. Thus, metformin may produce anorectic effects through modulation of NOS.

Adipose Tissue, Brown↗
PubMed2001

Effect of LPS on the permeability of the blood-brain barrier to insulin.

Insulin has emerged as an important neuropeptide. Central actions of insulin appear to oppose those in the periphery. Insulin is transported across the blood-brain barrier (BBB) by a saturable transport system. The permeability of the BBB to insulin is altered by various events, but no studies exist that have examined the permeability of the BBB to insulin during infection or inflammation, states which can induce peripheral insulin resistance. We looked at the effects of lipopolysaccharide (LPS), a bacterial endotoxin and a powerful cytokine releaser, on the permeability of the BBB to human insulin in CD-1 mice. Intraperitoneal injections of LPS significantly increased the uptake by the brain of 131I-insulin and disrupted the BBB to 125I-albumin. After subtraction of the brain/serum ratio for 125I-albumin, brain/serum ratios for insulin were increased: 10.38 +/- 0.70 microl/g (LPS) vs. 3.62 +/- 0.27 microl/g (no LPS), P<0.0001, showing that LPS increased the uptake of insulin independent of BBB disruption. This increase in insulin uptake was due to enhanced saturable transport. Pretreatment with indomethacin 10 min before LPS injections enhanced BBB disruption, but not insulin transport. Pretreatment with the nitric oxide (NO) synthase inhibitor aminoguanidine had no effect on insulin or albumin uptake, but pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) enhanced insulin transport, but not BBB disruption. We conclude that LPS increases the saturable transport of insulin across the BBB independent of disruption and prostaglandins with potentiation by NO inhibition. Such increased transport could potentiate the central effects of insulin and so contribute to the peripheral insulin resistance seen with infection and inflammation.

Animals↗
PubMed2001

Androgens and aging.

This review supports the conclusion that the use of testosterone replacement therapy for the treatment of the symptoms of androgen deficiency in aging males (ADAM) may be appropriate if undertaken with due caution. The best safety data exists for using oral therapy with testosterone undeconoate. Less data exists for the treatment of postmenopausal women with testosterone. Tibolone (an estrogen--prostagen--testosterone) compound, may make the need for testosterone being added to estrogen in women unnecessary. Less data is available to support the use of DHEA or its sulfate or pregnenolone. Further studies are clearly necessary in all these areas. However, it may be tentatively concluded that we are at the dawning of the age of androgens.

Aged↗
PubMed2001

Osteoporosis in men: are we ready to diagnose and treat?

Because osteoporosis and its attendant fractures are more common in women than in men, most studies have been performed in women. However, age-related osteoporosis and fragility fractures are also a major problem in men. Recent studies suggest that diagnosing men as osteoporotic when they fall more than 2.5 standard deviations below the mean for young men identifies a group at risk for fracture. Data suggest that many men with femoral fractures have age-related hypogonadism. Hypogonadism is associated with decreased lean body mass and bone mass. Most men with femoral fractures are reported to be hypogonadal. Testosterone replacement in hypogonadal older men improves bone mass and lean body mass. A therapeutic intervention to reduce fracture incidence in men with osteoporosis has been reported. No population-based study has examined the incidence or prevalence of hypogonadism with or without osteoporosis in men. Thus, osteoporosis in men probably exists with and without hypogonadism. Therapeutic interventions should be based on treatment of hypogonadism when present with osteoporosis.

Aging↗
PubMed2001

Utilizing pain assessment scales increases the frequency of diagnosing pain among elderly nursing home residents.

To study the effect of utilizing a combination of three easily-administered pain assessment instruments on the frequency of diagnosing pain among elderly nursing home residents, a cross-sectional study was conducted at two academic skilled nursing facilities: an 899-bed facility in Long Island, New York, and a 201-bed facility in Maryland Heights, Missouri. A total of 305 randomly selected elderly (>or= 60 years) subjects were enrolled in this study. The study involved medical records abstracting and patient interviews. Pain was assessed in 150 (49%) subjects using the question "Do you have pain?" (Group 1). In the remaining 155 (51%) subjects (Group 2), pain was assessed using three pain assessment instruments: the visual analog scale, the behavior (faces) scale, and the pain descriptive scale. The overall frequency of diagnosing pain was greater in the subjects in Group 2 compared to the subjects in Group 1 (30% vs. 15%, P < 0.01). Using the three pain assessment scales greatly increased the frequency of diagnosing pain among the old-old (>or= 85 years) residents (32% Group 2 vs. 6% Group 1, P < 0.001). The frequency of diagnosing pain among cognitively impaired residents showed a similar trend (16% Group 2 vs. 10% Group 1, P = 0.2). These data indicate that using three easily-administered pain assessment scales increased the frequency of diagnosing pain among nursing home residents.

Aged↗
PubMed2001

Hormone replacement therapy and fractures in older adults.

Estrogen deficiency in women is associated with accelerated bone loss, and estrogen replacement therapy has been proven to be effective in preventing osteoporosis and fractures in postmenopausal women. The introduction of selective estrogen receptor modulators that have an estrogen-like effect on the skeleton but have a different pattern of effects on other tissues may have an important role in the management of osteoporosis in women in the near future. In men, androgen deficiency has been shown to be associated with osteoporosis. Although androgen replacement in hypogonadal men may decrease bone resorption and increase bone mass, long-term placebo-controlled trials are needed to better define the benefits and risks of such therapy before it can be recommended. Sex hormone deficiency is linked to the development of osteoporosis in both women and men. In women, hormonal replacement by estrogen or the newly developed selective estrogen receptor modulators may prevent the development of osteoporosis and its related fractures. In men, there is early evidence that testosterone replacement therapy may enhance bone mass in hypogonadal men.

Age Distribution↗
PubMed2001

Effects of aging on the opioid modulation of feeding in humans.

OBJECTIVES: To determine whether aging is associated with a reduction in the opioid modulation of feeding, which may be important in the pathogenesis of the "anorexia of aging." DESIGN: Three studies on separate days, in randomized order and double-blind fashion. SETTING: Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. PARTICIPANTS: Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects. INTERVENTION: Subjects received in double-blinded random order, intravenous bolus (10 minutes) and then continuous (140 minutes) infusions of saline (control), naloxone low dose (LD) (bolus 27 microg/kg; continuous 50 microg/kg/hr), or naloxone high dose (HD) (bolus 54.5 microg/kg; continuous 100 microg/kg/hr). MEASUREMENTS: After 120 minutes, subjects were offered a buffet meal, and their energy intake was quantified. Hunger, fullness, nausea, and drowsiness were assessed using visual analogue scales. RESULTS: The naloxone LD and HD infusions had no significant effect on ratings of hunger, fullness, or nausea, but increased drowsiness (P < .01) compared with the control infusion in both age groups. Older subjects ate less (P < .001) at the buffet meal than young subjects during all three infusions. Naloxone infusions reduced energy intake compared with control (P < .001), LD by 13.2 +/- 5.0% and HD by 10.7 +/- 5.0%, with no difference between the doses (P = .71). Overall, naloxone suppressed energy intake in both young and older subjects (P < .01). This suppression was slightly, but not significantly, greater in young than in older subjects (mean of LD and HD 16.4 +/- 4.9% vs 7.5 +/- 4.9%, P = .42), because of a trend to reduced suppression in older women. CONCLUSIONS: We conclude that healthy older adults retain their sensitivity to the suppressive effects of naloxone on food intake. Possible gender differences in this sensitivity warrant further investigation. A decline in opioid activity is unlikely to contribute substantially to the physiological anorexia of aging observed in older people.

Adult↗
PubMed2001

Sarcopenia.

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the "fat frail") have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines-especially interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6-play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones-namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I-is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed.

Aging↗
PubMed2001

Food for thought.

Explore the source record for details and available documents.

Alzheimer Disease↗
PubMed2001

Decreased food intake with aging.

There is a physiological decline in food intake with aging. The reasons for the decline in food intake are multifactorial and involve both peripheral and central mechanisms. Altered hedonic qualities of food occur due to alterations in taste and, more particularly, smell with aging. A decline in adaptive relaxation of the fundus of the stomach and an increased rate of antral filling appear to play a role in the early satiation seen in many older persons. Cholecystokinin levels are increased with aging and older persons are more sensitive to the satiating effects of this gut hormone. The decline in testosterone levels in older males leads to increased leptin levels and this may explain the greater decline in food intake with aging in the male. Within the hypothalamus, decreased activity of both the dynorphin (kappa opioid) and neuropeptide Y systems occurs in aging rodents. Cytokines are potent anorectic agents. Many older persons have mild inflammatory disorders that lead to anorexia. Exercise may increase food intake in older persons.

Aged↗
PubMed2001

A student-run Geriatric Home Health Care Program.

This paper describes how medical students developed, maintained, and received curriculum credit for a home health care program for senior citizens, and how both patients and students have benefited from the program.

Aged↗
PubMed2001

Anorexia, body composition, and ageing.

Over the lifespan there is a decline in food intake. This has been termed the physiological anorexia of aging. It has many causes, including alterations in the gastrointestinal satiating system, the effect of elevated leptin levels, especially in men, and a variety of changes in central nervous system neurotransmitters. Beyond the age of 70 years body mass declines. This includes both loss of adipose tissue and muscle mass. The loss of muscle mass in older individuals is termed sarcopenia. There is increasing evidence that this is caused, in men, partly by the decline in testosterone. Illness results in an increase of cytokines that produce both anorexia and cause protein wasting. Many of the causes of cachexia in older individuals are treatable. Depression is the most common cause of weight loss in older individuals. Dieting in older individuals is associated with a loss of skeletal tissue as well as fat mass. This can place older individuals at risk of becoming the 'fat frail'.

Aged↗
PubMed2001

Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men.

OBJECTIVE: The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity. METHODS: Thirteen older (65-84 yr) and 13 young (18-32 yr) healthy men received isovolumetric, intraduodenal (i.d.) infusions of saline (control), lipid, and glucose for 120 min, on separate days. The energy content of the lipid and glucose infusions was identical at 2.86 kcal/min. Immediately after the i.d. infusions, each subject was offered a buffet meal, and ad libitum food intake was quantified. Blood glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide were measured. Gastric myoelectrical activity was measured by surface electrogastrography (EGG). RESULTS: I.d. lipid suppressed food intake in both the young and older men (p < 0.05), whereas i.d. glucose suppressed food intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin (p < 0.05) responses to i.d. glucose were greater in older than young men. However, there were no differences in glucagon-like peptide 1 or glucose-dependent insulinotropic peptide responses to any of the infusions. There was a greater increase in the EGG power ratio both during and after i.d. glucose infusion in the young (p < 0.05) than the older men, and an attenuation of EGG frequency by nutrient infusions in older, but not young, men. CONCLUSIONS: Our findings indicate that aging is associated with nutrient-specific changes in appetite, hormonal, and gastric myoelectrical (EGG) responses to i.d. nutrients. An enhanced satiating effect of small intestinal carbohydrates may potentially contribute to the anorexia of aging.

Adolescent↗
PubMed2001

Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.

Healthy aging is associated with reductions in appetite and food intake--the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on the satiating effects of CCK, 12 young and 12 older healthy subjects received 25-min iv infusions of saline (control) and CCK-8, 1 ng/kg per min or 3 ng/k per min, on 3 separate days before a test meal. Older subjects ate less than young subjects, and food intake was suppressed 21.6% by CCK-8, compared with the control day (P < 0.05). The suppression of energy intake by CCK-8 in older subjects was twice that in young subjects (32 +/- 6% vs. 16 +/- 6% SEM, P < 0.05) and was related to plasma CCK-8 concentrations, which were higher at baseline (P < 0.05) and increased more during CCK-8 infusions in older than young subjects (P < 0.01). The extent of suppression of food intake per given rise in plasma CCK-8 concentrations did not differ between the two age groups (P = 0.35). Endogenous CCK concentrations were higher at baseline in older subjects (P < 0.001) and decreased during the CCK-8 but not control infusions (P < 0.01), suggesting that CCK suppresses its own release. Plasma leptin concentrations were not affected by CCK infusion, whereas postprandial insulin concentrations were lowered and the peak postprandial glucose concentration was delayed but not affected by CCK-8 infusion. Because older people retain their sensitivity to the satiating effects of exogenous CCK and plasma endogenous CCK concentrations are higher in older people, increased CCK activity may contribute to the anorexia of aging.

Adult↗
PubMed2001

Serum leptin levels in wild and captive populations of baboons (papio): implications for the ancestral role of leptin.

Leptin has emerged as the major lipostat, regulating adiposity by affecting feeding behavior and thermogenesis. Leptin levels in normal-weight Western humans and in captive rodents are 5-15 ng/ml. But evidence suggests that these levels are abnormally high and that leptin may have evolved as a more general metabolic signal, with its most robust effects at lower levels. If this is true, then wild, healthy animal populations should have lower levels of leptin than captive populations and Western Man. We examined leptin levels in wild, East African populations of baboons (Papio anubis, P. hamadryas, and anubis/hamadryas hybrids). Serum leptin levels averaged less than 1 ng/ml, and no differences occurred in leptin levels among the species. In wild baboons, serum leptin levels were highest in the youngest baboons, with a trend toward an inverse relation between dental age and serum leptin levels. In comparison, captive baboons had levels about three times higher than wild baboons, with a clear inverse relation between age and leptin levels. These results support the view that leptin evolved to be effective at low levels.

Aging↗