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PubMed2006

Beneficial effect of moderate food restriction in toxicity studies in rats.

Moderate food restriction (FR) has been established as a nutritionally appropriate and well-controlled method with long-term beneficial effects in conducting toxicity and carcinogenicity studies in rodents. This study describes the early effects of moderate FR on toxicity study parameters in rats and on the variability of these parameters. Physical signs, body weight, food and water consumption, and clinical pathology parameters were examined in a 4-week study in which rats were moderately food-restricted or fed ad libitum (AL). There were no diet-related differences in physical signs, hematology or urinalysis. FR-related changes were observed in body weight and serum biochemistry; however, most of the changes involved anti-aging alterations and/or physiological adjustment to FR. Moderate FR resulted in low variability and good reproducibility in body weight. The present results indicate that moderate FR does not impair study parameters and increases statistical sensitivity. Therefore, a moderate FR feeding regimen is beneficial not only for long-term but also for short-term toxicity studies in rats.

Animals↗

PubMed1994

Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity.

OBJECTIVE: To test the hypothesis that insulin-mediated glucose uptake is enhanced in light-to-moderate alcohol consumption. RESEARCH DESIGN AND METHODS: This is a case-control study of healthy volunteers, divided into nondrinkers and light-to-moderate drinkers based on their history of alcohol consumption. The study was performed at the General Clinical Research Center at Stanford University Medical Center and involved 40 volunteers, 20 men and 20 women. Measurements were made of the plasma glucose and insulin responses to an oral glucose challenge, fasting plasma lipid and lipoprotein concentrations, and steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. RESULTS: Light-to-moderate drinkers (10-30 g/day) had lower integrated plasma glucose (17.8 +/- 0.8 vs. 19.8 +/- 0.9 mM/h, P < 0.02) and insulin (600 +/- 65 vs. 1,075 +/- 160 pM/h, P < 0.01) responses to the glucose challenge and higher fasting plasma high-density lipoprotein (HDL) cholesterol concentrations (1.46 +/- 0.08 vs. 1.25 +/- 0.08, P < 0.02). Despite similar SSPI concentrations of approximately 300 pM, SSPG concentrations were lower (P < 0.01) in light-to-moderate drinkers (6.7 +/- 0.8 vs. 10.7 +/- 1.2 mM). Results were independent of age, body mass index, ratio of waist-to-hip girth, and estimates of level of habitual physical activity. CONCLUSIONS: Light-to-moderate alcohol consumption in healthy men and women is associated with enhanced insulin-mediated glucose uptake, lower plasma glucose and insulin concentrations in response to oral glucose, and a higher HDL-cholesterol concentration. The changes in glucose and insulin metabolism may contribute to the lower risk of coronary heart disease described in light-to-moderate drinkers.

Adult↗

PubMed2006

Histomorphometric analysis of articular cartilage, zone of calcified cartilage, and subchondral bone plate in femoral heads from clinically normal dogs and dogs with moderate or severe osteoarthritis.

OBJECTIVE: To quantify and compare the microscopic changes in articular cartilage (AC), zone of calcified cartilage (ZCC), and subchondral bone plate in femoral heads from clinically normal dogs and dogs with moderate or severe osteoarthritis. SAMPLE POPULATION: Femoral heads from clinically normal dogs (n = 16) and dogs with moderate (24) or severe (14) osteoarthritis. PROCEDURES: Femoral heads were allocated to 3 categories (normal, moderate, or severe osteoarthritis) on the basis of radiographic findings, macroscopic findings, and histologic grade determined by use of a modified Mankin scale. Equally spaced 2-mm sections were cut in each femoral head in a coronal or transverse plane. Thickness of the AC, ZCC, and subchondral bone plate was recorded. RESULTS: Mean thickness of AC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the ZCC was significantly greater in samples with moderate and severe osteoarthritis than those considered normal. Mean thickness of the subchondral bone plate in samples with severe osteoarthritis was significantly greater than those with moderate osteoarthritis and those considered normal. A significant decrease in AC thickness was detected in the proximomedial area of femoral heads with severe osteoarthritis, compared with those considered normal. CONCLUSIONS AND CLINICAL RELEVANCE: A cause and effect association between thickening of subchondral structures and thinning and loss of the overlying AC was not detected. Changes in AC were associated with changes in the subchondral bone plate, which is compatible with the theory of adaptation in response to altered load distribution.

Animals↗

PubMed2002

Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury.

OBJECT: The aim of this study was to investigate the effects of moderate hyperventilation on intracranial pressure (ICP), jugular venous oxygen saturation ([SjvO2], an index of global cerebral perfusion), and brain tissue PO2 (an index of local cerebral perfusion). METHODS: Ninety-four tests consisting of 20-minute periods of moderate hyperventilation (27-32 mm Hg) were performed on different days in 36 patients with severe traumatic brain injury (Glasgow Coma Scale score < or = 8). Moderate hyperventilation resulted in a significant reduction in average ICP, but in seven tests performed in five patients it was ineffective. The response of SjvO2 and brain tissue PO2 to CO2 changes was widely variable and unpredictable. After 20 minutes of moderate hyperventilation in most tests (79.8%), both SjvO2 and brain tissue PO2 values remained above the lower limits of normality (50% and 10 mm Hg, respectively). In contrast, in 15 tests performed in six patients (16.6% of the studied population) brain tissue PO2 decreased below 10 mm Hg although the corresponding SjvO2 values were greater than 50%. The reduction of brain tissue PO2 below 10 mm Hg was favored by the low prehyperventilation values (10 tests), higher CO2 reactivity, and, possibly, by lower prehyperventilation values of cerebral perfusion pressure. In five of those 15 tests, the prehyperventilation values of SjvO2 were greater than 70%, a condition of relative hyperemia. The SjvO2 decreased below 50% in four tests; the corresponding brain tissue PO2 values were less than 10 mm Hg in three of those tests, whereas in the fourth, the jugular venous O2 desaturation was not detected by brain tissue PO2. The analysis of the simultaneous relative changes (prehyperventilation - posthyperventilation) of SjvO2 and brain tissue PO2 showed that in most tests (75.5%) there was a reduction of both SjvO2 and brain tissue PO2. In two tests moderate hyperventilation resulted in an increase of both SjvO2 and brain tissue PO2. In the remaining 17 tests a redistribution of the cerebral blood flow was observed, leading to changes in SjvO2 and brain tissue PO2 in opposite directions. CCONCLUSIONS. Hyperventilation, even if moderate, can frequently result in harmful local reductions of cerebral perfusion that cannot be detected by assessing SjvO2. Therefore, hyperventilation should be used with caution and should not be considered safe. This study confirms that SjvO2 and brain tissue PO2 are two parameters that provide complementary information on brain oxygenation that is useful to reduce the risk of secondary damage. Changes in SjvO2 and brain tissue PO2 in opposite directions indicate that data obtained from brain tissue PO2 monitoring cannot be extrapolated to evaluate the global cerebral perfusion.

Adolescent↗

PubMed2003

Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia.

OBJECT: This study was performed to determine whether moderate hypothermia (31 degrees C) improves clinical outcome in severely head injured patients whose intracranial hypertension cannot be controlled using mild hypothermia (34 degrees C). METHODS: Twenty-two consecutive severely head injured patients who fulfilled the following criteria were included in this study: an intracranial pressure (ICP) that remained higher than 40 mm Hg despite the use of mild hypothermia combined with conventional therapies; and a Glasgow Coma Scale score of 8 or less on admission. After the failure of mild hypothermia in combination with conventional therapies; patients were exposed to moderate hypothermia as quickly as possible. As brain temperature was reduced from 34 to 31 degrees C, the volume of intravenous fluid infusion was increased significantly from 1.9 +/- 0.9 to 2.6 +/- 1.2 mg/kg/hr (p < 0.01), and the dose of dopamine infusion increased significantly from 4.3 +/- 3.1 to 8.2 +/- 4.4 microg/kg/min (p < 0.01). Nevertheless, mean arterial blood pressure and heart rate decreased significantly from 97.1 +/- 13.1 to 85.1 +/- 10.5 mm Hg (p < 0.01) and from 92.2 +/- 13.8 to 72.2 +/- 14.3 beats/minute at (p < 0.01) at 34 and 31 degrees C, respectively. Arterial base excess was significantly aggravated from -3.3 +/- 4 at 34 degrees C to -5.6 +/- 5.4 mEq/L (at 31 degrees C; p < 0.05). Likewise, serum potassium concentration, white blood cell counts, and platelet counts at 31 degrees C decreased significantly compared with those at 34 degrees C (p < 0.01). In 19 (86%) of 22 patients, elevation of ICP could not be prevented using moderate hypothermia. In the remaining three patients. ICP was maintained below 40 mm Hg by inducing moderate hypothermia; however, these three patients died of multiple organ failure. These results clearly indicate that moderate hypothermia induces complications more severe than those induced by mild hypothermia without improving outcomes. CONCLUSIONS: The authors concluded that moderate hypothermia is not effective in improving clinical outcomes in severely head injured patients whose ICP remains higher than 40 mm Hg after treatment with mild hypothermia combined with conventional therapies.

Adolescent↗

PubMed2001

Elevation of blood NAD level after moderate exercise in young women and mice.

We previously reported that the blood NAD levels are decreased by severe exercise, and administration of nicotinamide, a precursor of NAD, improves the endurance capacity of mice. In the present study, we determined whether moderate exercise changes the blood NAD levels in humans and mice. College female students exercised moderately with bike-ergometers. The blood NAD levels elevated after moderate exercise. Mice were forced to swim in a running water pool for 5 min as a moderate exercise, 15 min as a strong exercise, and until exhaustion as a severe exercise (average swimming time was 28.7 min). A 5 min swim gave a result similar to that of moderate exercise by human subjects. However, the blood NAD levels decreased after all-out exercise. The changes in whole blood tryptophan (a precursor of pyridine nucleotides) levels were similar to that in NAD. The glucose levels in whole blood and the non-esterified fatty acid levels in serum decreased according to exercising time. These data are the first demonstration of moderate exercise raising the blood NAD levels in human and mice. Elevation of the blood NAD levels may reflect changes in niacin metabolism that occur in response to exercise.

Adult↗

PubMed1984

Moderator effects on recoil tritium reactions with lithium beta-phenylpropionate.

The recoil tritium reactions were studied with lithium beta-phenylpropionate having both the aromatic and aliphatic C-H bonds in the molecule, mainly in terms of the moderator effect on the intramolecular tritium distribution. Recoil tritium atoms were produced by the 6Li(n,alpha)3H reaction. Water molecules were used as the moderator. The tritium activity of the ethylene group represented relative to that of the corresponding ring assumed as a standard (= 100) is 30 in the moderator-free system and is reduced to 13 in the moderated system in which the H2O/beta-PhC2H4CO2Li mole ratio is 328. In the ring, the tritium distribution shows a slight ortho- and para-orientation in the moderator-free system and the selectivity is pronounced when the H2O/beta-PhC2H4CO2Li mole ratio is large. The data show that the aromatic ring tritiation in the moderated system is given by increasing contribution of the reactions of tritium atoms having lower energy than the threshold energy of the ethylene group tritiation.

Lithium↗

PubMed1999

Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure.

PURPOSE: To investigate the hypothesis that nitric oxide (NO) in the optic nerve heads of rats with chronic moderately elevated intraocular pressure (IOP) contributes to neurotoxicity of the retinal ganglion cells, the presence of the three isoforms of nitric oxide synthase (NOS) was determined in the tissue. METHODS: Unilateral chronic moderately elevated IOP was produced in rats by cautery of three episcleral vessels. Histologic sections of optic nerves from eyes with normal IOP and with chronic moderately elevated IOP were studied by immunohistochemistry and by immunoblot analysis. Polyclonal antibodies to NOS-1, NOS-2, NOS-3, and glial fibrillary acidic protein (GFAP) were localized with immunoperoxidase. RESULTS: In the optic nerve of rat eyes with normal IOP, NOS-1 was constitutively present in astrocytes, pericytes and nerve terminals in the walls of the central artery. NOS-2 was not present in eyes with normal IOP. In these eyes, NOS-3 was constitutively present in the vascular endothelia of large and small vessels. Rat eyes treated with three-vessel cautery had sustained elevated IOP (1.6 fold) for at least 3 months. In these eyes, no obvious changes in NOS-1 or NOS-3 were noted. However, at time points as early as 4 days of chronic moderately elevated IOP, NOS-2 appeared in astrocytes in the optic nerve heads of these eyes and persisted for up to 3 months. Immunoblot analysis did not detect differences in NOS isoforms. CONCLUSION: The cellular distributions of constitutive NOS isoforms in the rat optic nerve suggest physiological roles for NO in this tissue. NOS-1 in astrocytes may produce NO as a mediator between neighboring cells. NO, produced by NOS-1 in pericytes and nitrergic nerve terminals and by NOS-3 in vascular endothelia, is probably a physiological vasodilator in this tissue. In eyes with chronic moderately elevated IOP, NOS-2 is apparently induced in astrocytes. The excessive NO production that is associated with this isoform may contribute to the neurotoxicity of the retinal ganglion cells in eyes with chronic moderately elevated IOP.

Animals↗

PubMed2000

Inactive aldehyde dehydrogenase 2 worsens glycemic control in patients with type 2 diabetes mellitus who drink low to moderate amounts of alcohol.

BACKGROUND: Alcohol intake can have hypoglycemic or hyperglycemic effects in patients with type 2 diabetes mellitus. The present study was designed to investigate the glycemic control of male patients with diabetes mellitus from the aspect of the genetic status of alcohol metabolism. METHODS: One hundred sixty-three men with type 2 diabetes mellitus were enrolled in the present study. They were all outpatients at the Diabetes Center of Saiseikai Central Hospital. The genotype of the aldehyde dehydrogenase 2 (ALDH2) gene of each patient was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the patients were divided into those with active or inactive ALDH2 phenotype. We compared the amount of habitual alcohol intake and clinical data that included physical findings and blood chemistry of the patients in the active and inactive ALDH2 groups. The glycemic control of each patient was evaluated by the serum level of HbAlc. RESULTS: Of the 163 patients with type 2 diabetes mellitus, 90 patients had the active ALDH2 phenotype and 73 patients had the inactive ALDH2 phenotype. The mean HbA1c level of the active ALDH2 group was nearly the same as that of the inactive ALDH2 group. However, the HbA1c level of the light-to-moderate drinkers (1-400 g/week) in the inactive ALDH2 group was highest and was significantly higher than the HbA1c level of the light-to-moderate drinkers of the active ALDH2 group. The HbA1c of the patients with diabetic complications was higher than the HbAlc of those without diabetic complications in both the active and inactive ALDH2 groups. However, the HbA1c level of the light-to-moderate drinkers without diabetic complications in the inactive ALDH2 group was significantly higher and the incidence of 24 hr urinary C-peptide was higher than the respective level of the light-to-moderate drinkers without diabetic complications in the active ALDH2 group. CONCLUSIONS: Habitual light-to-moderate alcohol intake worsens glycemic control in diabetic patients who have the inactive ALDH2 phenotype. The data on 24 hr urinary C-peptide level suggested that increased acetaldehyde after light-to-moderate drinking by inactive ALDH2 diabetic patients may increase the HbA1c value by the insulin-resistant condition that resulted in hyperinsulinemia.

Adult↗

PubMed1992

Purinergic vasoconstrictor component revealed by moderate cooling in the isolated mesenteric vasculature of Sprague-Dawley rats.

In the isolated mesenteric vasculature of rats, moderate cooling significantly augments the perfusion pressure responses to transmural field stimulation (TFS), whereas it depresses markedly TFS-induced endogenous norepinephrine (NE) release. Moderate cooling also reduces the perfusion pressure responses to exogenous NE. The present experiments, therefore, were performed to analyze further the mechanism of the augmented pressor responses to TFS during moderate cooling. NE release from the entire mesenteric vasculature was monitored along with the perfusion pressure response to periarterial nerve stimulation (4-14 Hz) at 37 or 24 degrees C. Prazosin (3 x 10(-8) M) abolished the pressor responses to TFS at 37 degrees C but not at 24 degrees C. Furthermore, prazosin abolished the pressor responses to exogenous NE at both temperatures. The TFS-induced pressor responses observed in the presence of prazosin at 24 degrees C were abolished by alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-Me ATP) (3 x 10(-6) M). alpha, beta-Me ATP significantly decreased the pressor responses to TFS at 24 degrees C but not 37 degrees C. Moderate cooling significantly augmented the vasoconstrictor response to alpha, beta-Me ATP per se. These drugs did not influence the TFS-induced endogenous NE release at either temperature. These results suggest that moderate cooling reveals that ATP or related purines released from sympathetic nerves act as cotransmitters in the isolated mesenteric vasculature of rats. That is, augmented pressor responses to TFS during moderate cooling appeared to be due, at least in part, to a purinergic component.

Animals↗

PubMed2005

Moderate drinking and cardiovascular disease.

The adverse consequences of heavy alcohol use are well known. However, recent media reports of a possible cardiovascular benefit associated with moderate drinking have revived public interest in the use of alcohol for "medicinal purposes." Knowledge development regarding guidelines for moderate alcohol use has lagged behind public interest in the possible health benefits of moderate alcohol use. At this time, evidence-based primary health promotion interventions related to the risks and benefits of moderate alcohol use are lacking in the health care literature. This chapter reviews 22 reports describing the relationship between moderate drinking and cardiovascular disease. The reports are classified by the level of evidence and critiqued on seven aspects of method. Conclusions related to the strength of the evidence that moderate drinking is a useful primary health promotion intervention are presented.

Alcohol Drinking↗

PubMed2006

[Comparison of intensive and moderate individual life-style intervention programs for overweight or obese persons with fasting glucose levels of 95-125 mg/dl in Japan].

OBJECTIVES: There are considerable differences in individual health education programs for persons at high risk of type 2 diabetes between ordinary Japanese life-style modification programs and the Diabetes Prevention Program in the US, the former being relatively moderate and the latter more intensive. We therefore compared the effectiveness of intensive and moderate intervention, focusing on the frequency of individual educational classes. METHODS: The subjects were men and women aged 44-69 years living in Nishiaizu town, Fukushima prefecture in Japan. Their fasting plasma glucose concentration was between 95 and 125 mg/dl at health examinations conducted in 2002 or 2003. They also had a body mass index (BMI) of 23.0 or higher, a fasting plasma glucose concentration of 125 mg/dl or lower and a post-load plasma glucose concentration (2 h) of 199 mg/dl or lower in the 2004 survey. We assigned the subjects according to their residences to an intensive life-style intervention group (two education classes per month; n = 11) or a moderate intervention group (one education class per month; n = 14). The main outcome measure was the change in body weight after 6 months of intervention. RESULTS: The loss of body weight was -3.5 kg (P< .0001) in the intensive intervention group and -1.8 kg (P = 0.02) in the moderate group, and the net difference in body weight loss between the groups was -2.0 kg (95% confidence interval -4.0 to -0.05; P = 0.045) after adjustment for age, sex, and baseline body weight. BMI and subcutaneous fat area showed similar results. The post-load plasma glucose concentration (2 h) and other tested values showed no significant net change between the two groups. CONCLUSIONS: Intensive and moderate intervention both reduced body weight in overweight or obese persons at high risk of type 2 diabetes. The intensive intervention, two sessions of individual education classes per month, was significantly more effective than the moderate one for reducing body weight.

Adult↗

PubMed2006

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40-65 years: 5-year follow up.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.

Adult↗

PubMed2006

Efficacy and safety of tacrolimus ointment in pediatric Patients with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an immunological skin disease. It is common in pediatric populations and often requires topical steroid treatment. Moderate to severe AD may not respond to topical steroids. They often require systemic steroids, which may result in growth retardation. Protopic, a non-steroid, tacrolimus based ointment which is a calcinurin inhibitor has been proved to be effective in caucacian with AD. OBJECTIVE: To evaluate safety and efficacy of 0.03% tacrolimus ointment (Protopic&) in moderate to severe AD in pediatric patients age 2-12 years. MATERIAL AND METHOD: This was a one month multicenter open-label clinical trial using tacrolimus ointment twice daily in 61 subjects with moderate to severe AD from September to December 2004. Efficacy assessments were measured by Physician's Global Evaluation of Clinical Response (PhGECR), Eczema area and Severity Index (EASI), Patient's Global Evaluation of Clinical Response (PaGECR), and Quality of Life (QOL). Safety assessment was measured by incidence rate of adverse events. RESULTS: Fifty-eight patients completed the studies. Twenty-two patients were male; thirty-nine patients were female. Twenty-nine patients had moderate AD. Thirty-two patients had severe AD. Three cases had discontinued treatment at the third week due to increase in severity. Over all PhGECR were significantly increased, 94% showed moderate improvement in PhGECR at week 4 or end of treatment (EOT)and 83% had better improvement in PaGECR at EOT Within 7 days, tacrolimus demonstrated rapid onset in reduction of EASI score and itch in patients. Mean QOL were significantly decreased at the end of the present study. Incidence of adverse events included application site burning (21%), itching (17%), pruritus (9%), infections(3%), and erythema and folliculitis (2%). Burning sensation, erythema, pruritus and itching were resolved after the first week. CONCLUSION: Topical tacrolimus ointment is effective and safe in moderate to severe AD. It significantly improved PhGECR, EASI, PaGECR, and QOL in pediatric patients after the first week of treatment and continued through the end of the study. The major adverse events were burning, itching, and pruritus, which were resolved within the first week of therapy.

Administration, Topical↗

PubMed1990

Baboon alcohol dehydrogenase isozymes: purification and properties of liver class I ADH. Moderate alcohol consumption reduces liver class I and class II ADH activities.

The major baboon liver isozyme of alcohol dehydrogenase (ADH-2) has been purified to homogeneity by affinity chromatography, and characterized as a "typical" Class I mammalian ADH isozyme. In contrast to human liver, which possesses three genetic isozymes (alpha 2, beta 2, and gamma 2) and three hybrid isozymes (alpha beta, alpha gamma, and beta gamma) of Class I ADH, baboon liver exhibits activity of a single major Class I isozyme (beta 2). Kinetic analyses, using alcohol substrates of differing chain lengths, and inhibition with pyrazole, support this classification. Agarose-IEF analyses, substrate specificity studies and immunochemical titrations of the major kidney ADH (ADH-1) also support the occurrence of a second Class I isozyme. The baboon was used as a model to study alcohol-induced changes in liver ADH phenotype following moderate and moderately high alcohol consumption. Four male and four female prepubertal baboons were fed nutritionally adequate liquid diets over a 40-week period, including control diets (weeks 1-8, 17-24, 32-40), moderate (12.5 percent of calories) alcohol diet (weeks 9-16), and a moderately high (25 percent of calories) alcohol diet (weeks 25-32). Liver ADH isozyme patterns and Class I ADH activities from biopsy samples, taken every 4 weeks, were monitored during the feeding study. Decreases in both Class I and Class II ADH activities were indicated in most animals, which may reflect adaptive mechanisms in the liver to continuing alcohol metabolism. Moreover, reversible changes were observed, with trends toward a recovery of ADH isozyme activities following return to the control liquid diets. These studies also have particular significance for human biomedical research work on alcohol, since most of the "drinking" population in typical drinking communities are moderate consumers of alcohol. This work, using the baboon as an animal model, has clearly indicated that alcohol consumption at such moderate levels, brings with it adaptations in the level of ADH isozymes in liver, which may play a protective role.

Alcohol Dehydrogenase↗

PubMed1986

Effect of moderate vitamin A supplementation and lack of dietary vitamin A on the development of mammary tumors in female rats treated with low carcinogenic dose levels of 7,12-dimethylbenz(a)anthracene.

We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12-dimethylbenz(a)anthracene. The number of mammary tumors was significantly (P less than 0.05) reduced if prior to and during initiation with 7,12-dimethylbenz(a)anthracene the rats were fed a moderately increased (30 micrograms/day) or marginal (3 micrograms/day) amount of vitamin A, compared to rats fed an adequate (10 micrograms/day) amount of vitamin A. The number of mammary tumors was also significantly (P less than 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly (P less than 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum-fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant (P less than 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 micrograms/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 micrograms/day) intake of vitamin A, that resulted in a small, but statistically significant (P less than 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors. These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

[Clinical prognosis of moderate restenosis after percutaneous transluminal coronary angioplasty].

Follow-up angiography after percutaneous transluminal coronary angioplasty (PTCA) often demonstrates "moderate" angiographic restenosis, but the need for subsequent revascularization is difficult to determine. We examined the clinical outcome of patients with moderate angiographic restenosis after PTCA. Follow-up angiography performed in 96 patients within 4 months showed light restenosis (LR:stenosis < 40%) in 52 patients, moderate restenosis (MR:40-70%) in 21, and severe restenosis (SR: > 70%) in 23. One of 21 patients with MR underwent repeat PTCA after a positive exercise test. The remaining 20 patients with MR were compared with 52 with LR (follow-up: 12-18 months). Five patients with MR underwent repeat PTCA for recurrence of angina in the follow-up period. Log rank analysis of the Kaplan-Meier estimates for event-free survival (death, myocardial infarction CABG, re-PTCA) showed the outcome was significantly worse for MR patients. However, 14 MR patients who had no cardiac event demonstrated regression of stenosis at 1-year follow-up angiography (58.2% to 45.4%). Moderate restenosis at angiographic follow-up was observed in 30% of all PTCA patients. Moderate restenosis patients have a worse prognosis than light restenosis patients. Adequate follow-up management is mandatory for moderate restenosis patients.

Aged↗

PubMed1997

Moderate-intensity exercise and self-rated quality of sleep in older adults. A randomized controlled trial.

OBJECTIVE: To determine the effects of moderate-intensity exercise training on self-rated (subjective) sleep quality among healthy, sedentary older adults reporting moderate sleep complaints. DESIGN: Randomized controlled trial of 16 weeks' duration. SETTING: General community. PARTICIPANTS: Volunteer sample of 29 women and 14 men (of 67 eligible subjects) aged 50 to 76 years who were sedentary, free of cardiovascular disease, and reported moderate sleep complaints. No participant was withdrawn for adverse effects. INTERVENTION: Randomized to 16 weeks of community-based, moderate-intensity exercise training or to a wait-listed control condition. Exercise consisted primarily of four 30- to 40-minute endurance training sessions (low-impact aerobics; brisk walking) prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill exercise heart rate. MAIN OUTCOME MEASURE: Pittsburgh Sleep Quality Index (PSQI). RESULTS: Compared with controls (C), subjects in the exercise training condition (E) showed significant improvement in the PSQI global sleep score at 16 weeks (baseline and posttest values in mean [SD] for C=8.93 [3.1] and 8.8 [2.6]; baseline and posttest values for E=8.7 [3.0] and 5.4 [2.8]; mean posttest difference between conditions=3.4; P<.001; 95% confidence interval, 1.9-5.4), as well as in the sleep parameters of rated sleep quality, sleep-onset latency (baseline and posttest values for C=26.1 [20.0] and 23.8 [15.3]; for E=28.4 [20.2] and 14.6 [13.0]; net improvement=11.5 minutes), and sleep duration baseline and posttest scores for C=5.8 [1.1] and 6.0 [1.0]; for E=6.0 [1.1] and 6.8 [1.2]; net improvement=42 minutes) assessed via PSQI and sleep diaries (P=.05). CONCLUSIONS: Older adults with moderate sleep complaints can improve self-rated sleep quality by initiating a regular moderate-intensity exercise program.

Aged↗