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Biomedical subjects

M L Kaplan

Publications and source records attributed to M L Kaplan.

At least 37 records · Page 2Linked to original sources

The self-organization of human psychological functioning.

This article describes the traditional model of human psychological functioning which dominates current theorizing, contrasts it with the new, emerging perspective of self-organizing processes, and applies this new approach to a theory of human psychological functioning. In the traditional model there is an assumption that processes of functioning are discretely different from physical structure. This assumption is shown to be intrinsic to a linear conceptual framework which implies that (a) stability of functioning derives from physical structure; (b) functioning is determined by the effects of enduring, antecedent components; (c) the environment can selectively influence structure; and (d) observational methods are capable of accessing and revealing processes of functioning. In the contrasting self-organizational perspective, structure and functioning are assumed to be given in one another at the level of organizational process. This formulation implies that as a system functions (a) its orderliness and stability are being determined by the ongoing functioning itself; (b) at the level or organizational functioning there are no antecedent structures separate from consequent activity; (c) systemic functioning exists as a unitary and continuous organizational process; and (d) organizational functioning cannot be instructed by environmental events. The work of Prigogine and of Maturana are examined as a basis for a theory of human psychological functioning as a self-organizing system. The theory that is proposed describes how attentional and experiential functioning evolve as a system of organizational continuity and coherence and how the process by which people recognize and identify their functioning secures this organizational functioning.

Adaptation, Psychological↗

Inhibition of alveolar bone loss in beagles with the NSAID naproxen.

The non-steroidal anti-inflammatory drug(NSAID) naproxen was studied in 11 beagle dogs over a 13-month period to determine its effect on the progression of periodontitis. Following a 6-month pretreatment period, 5 dogs received naproxen daily at a dosage of 2.0 mg/kg for 1 month, then 0.2 mg/kg for 6 months. Six control dogs received a gelatin capsule daily as placebo. Standardized radiographs were used to measure the rate of bone loss during the pretreatment and treatment periods. In the control dogs, the rate of bone loss was seen to increase during the treatment period although the increase was not statistically significant. In dogs treated daily with naproxen, the rate of bone loss in the treatment period was significantly less at 4 months of treatment; however, at 7 months the difference, though lower than pretreatment rate, was not significant. When the percent change in rate of bone loss during the overall 7-month treatment period was compared with pretreatment rate, the control dogs demonstrated a 38% increase in rate of bone loss during the treatment period contrasting with a 61% decrease in bone loss rate in naproxen-treated dogs. The data indicate that the non-steroidal anti-inflammatory drug naproxen can significantly inhibit alveolar bone loss in beagles. At 4 months of treatment the rate of bone loss in the naproxen-treated dogs was significantly less than pretreatment, but at 7 months of treatment the rate was no longer statistically significantly less than baseline. This probably reflects a dose response to naproxen treatment for, after 30 days of the treatment period, the naproxen dosage was reduced 10-fold due to tolerance by the beagle.

Alveolar Bone Loss↗

Oxygen consumption of muscles from ob/ob and Ay/a strains of obese mice.

Oxygen consumption was measured in the in vitro preparations of soleus, extensor digitorum longus, gracilis, and diaphragm muscles from young ob/ob obese mice. In young Ay/a obese mice, similar measurements were made with in vitro preparations of soleus, gracilis, and diaphragm muscles. These young obese mice were heavier than their nonobese littermates. Muscle weights were similar in obese and nonobese mice. In the Ay/a obese mice, values of muscle oxygen consumption were similar to those found in the a/a nonobese littermates. This correlates well with other known information about the Ay/a variety of obesity. In the ob/ob obese mice, values of oxygen consumption in the gracilis and diaphragm muscle preparations were lower than those in nonobese littermates. These data indicate that some muscles in the ob/ob obese mice contribute to the depressed whole animal oxygen consumption by virtue of defective oxidative metabolism. The data also indicate that the tissue defects are very different in various types of obese animal models. This probably is also true for different types of human obesity.

Animals↗

The effect of triiodothyronine on glucose utilization in adipocytes from obese rats.

1. In the presence of insulin, 10(-5) M 3,3',5-triiodothyronine (T3) treatment for 1/2 hr decreased fatty acid synthesis 35% only in adipocytes from lean rats, whereas at 10(-11) M through 10(-7) M T3 the obese adipocytes had nearly a 20% increase in fatty acid synthesis. 2. A 2 hr pretreatment of adipocytes with 10(-9) and 10(-7) M T3 decreased insulin-stimulated fatty acid synthesis by nearly 20% in both lean and obese adipocytes. 3. In the absence of insulin, the 2 hr pretreatment with 10(-9) M T3 resulted in a 45% increase in lean adipocyte fatty acid synthesis, though the obese adipocytes required at least 10(-7) M T3 for 2 hr to increase the non-insulin-stimulated fatty acid synthesis by 50%. 4. At 10(-9) M T3 concentrations non-insulin-stimulated fatty acid synthesis was increased by 200% in lean adipose tissue explants, but obese adipose explants were not significantly affected under these conditions. 5. The addition of 10(-9) M T3 plus insulin to the explant media decreased fatty acid synthesis by 35% in both the lean and obese tissues. 6. The results also imply that the low T3 status of the obese rat may be contributory to the elevated fatty acid synthesis observed in obese adipocytes.

Adipose Tissue↗

Age-related changes in sucrase and lactase activity in the small intestine of 3- and 10-week-old obese mice (C57BL/6Jobob).

The relationship between obesity and the digestion of carbohydrates is poorly understood. Data in humans have provided conflicting results. Studies using the obese mouse (C57BL/6Jobob) suggest that obesity is associated with increased activity of intestinal alpha-disaccharidases. To evaluate the developmental pattern of these enzyme activities in obesity, we determined the activity of sucrase and lactase in the small intestine of genetically obese mice (C57BL/6Jobob) and lean littermates at 3 and 10 weeks of age. Sucrase and lactase activities were measured on intestinal homogenates from segments of the small intestine in mice maintained on standard laboratory diets during the postweaning period. Results were expressed as specific activity and total activity per intestinal segment. Obese mice did not differ from lean littermates in body weight at 3 weeks of age, but exhibited increased protein content in the proximal small intestine. Sucrase specific activity was significantly higher in the obese mice at 3 weeks of age in all intestinal segments. Sucrase total activity showed a similar pattern. At 10 weeks of age, body weights of obese mice were substantially greater than the lean littermates. Sucrase specific and total activities were also greater in the obese mice at 10 weeks of age. Lactase specific activity, however, was similar in both obese and lean mice at both ages studied. Lactase total activity was greater in the obese mice, consistent with their greater intestinal mass. These observations demonstrate that changes in the intestinal sucrase activity of the obese mouse precede the development of excessive body weight.

Age Factors↗

Synthesis and evaluation of (17 alpha,20E)21-[125I]iodo-11-substituted-19-norpregna-1,3,5(10), 20-tetraene-3,17 beta-diols: the influence of 11-stereochemistry on tissue distribution of radioiodinated estrogens.

The 21-tri-n-butylstannyl derivatives of (17 alpha,20E)-11 alpha and beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol were synthesized and characterized. These compounds, as well as the 11-unsubstituted compound were converted via electrophilic ipso radioiododestannylation to the corresponding 21[125I]iodo analogs at the no-carrier-added level in 73-90% isolated radiochemical yields. The radiochemical 4c [IV alpha ME2, (17,20E)-21[125I]iodo-11 alpha-methoxy-19-norpregna-1,3, 5(10),20-tetraene-3,17 beta-diol] was evaluated in immature female rats and the results compared to those previously reported for 4a (IVE2) and 4b (IV beta ME2) to determine the influence of 11-substitution on the ability of the compounds to function as estrogen receptor-seeking agents in vivo. The results indicated that the uptake of 11 alpha-methoxy derivative in the target organ was substantially lower, of shorter duration, with a much smaller specific receptor binding component than the other two radioligands. The distribution profile of the three 17 alpha-iodovinyl estrogens paralleled that previously reported for the corresponding 17 alpha-ethynyl estrogens and this study suggests that the in vivo pharmacological results reported for the 17 alpha-ethynyl estrogens may be used to predict the in vivo behavior of the corresponding 17 alpha-iodovinyl analogs.

Animals↗

Effect of triiodothyronine on glucose utilization in diaphragm of obese (ob/ob) mice.

Genetically obese-hyperglycemic (ob/ob) mice are hypothyroid, hyperinsulinemic, and insulin resistant. Because muscle plays an important role in glucose homeostasis, the role of triiodothyronine (T3) in regulation of insulin-sensitive glucose utilization by muscles of obese mice was examined. Four doses of T3, 5.0, 12.5, 25.0, and 50.0 micrograms/100 g body weight were injected, i.p., into obese and nonobese mice daily from 3 weeks until 6 weeks of age. Food consumption and body weight were decreased at lower doses of T3 and increased at higher doses of T3 in both obese and nonobese mice. By 6 weeks of age all doses of T3 treatment increased oxygen consumption in both genotypes. At 6 weeks of age, the diaphragms from the saline-injected nonobese mice had greater in-vitro insulin-stimulated glucose utilization than muscles from the saline-injected obese mice. Both anaerobic and aerobic glucose oxidation were increased by T3 treatment, but the obese had greater increases than those observed in muscles from nonobese mice. Muscles from obese mice increased insulin-stimulated glucose utilization by T3 treatment to that of the nonobese level, whereas there was no change in insulin-stimulated glucose utilization of nonobese mice. Muscle glycogen synthesis in obese and nonobese mice was decreased with very high T3 doses. A higher dose of T3 was required to increase glucose utilization in the obese muscles than in the nonobese muscles. The results suggest that a functional hypothyroidism or T3 resistance may be an early part of this particular obesity syndrome.

Animals↗

Developmental changes of selected minerals in Zucker rats.

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/fa rats was less than that of non-fa/fa rats at 12 weeks of age; mean brain protein concentration was greater in fa/fa than in non-fa/fa at 5 and 12 weeks of age. At 18-19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fa was less than that of non-fa/fa. At 5 weeks of age, mean copper concentration (microgram/g protein) in kidney was greater in fa/fa. Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fa than in non-fa/fa at 5 weeks because of the larger livers and kidneys of fa/fa. Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6-10%) less in fa/fa than in non-fa/fa at 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fa than in non-fa/fa. However, total amount of each mineral in muscle at 12 weeks was less in fa/fa than in non-fa/fa because of the smaller mean muscle weight of fa/fa. Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fa than in non-fa/fa at 12 weeks. The major age-related changes in fa/fa that were not observed in non-fa/fa were large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.

Age Factors↗

Circadian changes in serum and liver metabolites and liver lipogenic enzymes in ad libitum- and meal-fed, lean and obese Zucker rats.

Circadian rhythms were studied in ad libitum- and meal-fed Zucker rats. Lean and obese female rats were fed ad libitum or in a single meal from 1400-1800 for 12 d. Both groups of ad libitum-fed rats exhibited a nocturnal feeding pattern; obese rats ate more than the lean rats during the light and dark parts of the cycle. After 12 d, groups of rats were killed at 4-h intervals over a 24-h period, inclusively, and the presence of circadian rhythms was evaluated for the serum metabolites, liver constituents and the liver lipogenic enzymes. The obese ad libitum-fed rats demonstrated rhythms for serum triglycerides, serum cholesterol, liver protein and glycogen, and the activities of fatty acid synthetase, citrate cleavage enzyme (EC 4.1.3.8), and glucose-6-P dehydrogenase (EC 1.1.1.49). Meal feeding the obese rats modified the rhythms for serum cholesterol, liver glycogen and the activities of glucose-6-P dehydrogenase, and citrate cleavage enzyme and a rhythm was established for serum glucose. The feeding schedule did not cue a rhythm for serum triglycerides and phosphogluconate dehydrogenase (EC 1.1.1.44) or modify the rhythm for liver protein. The lean ad libitum-fed rats displayed rhythms for all the measured parameters except serum glucose. Feeding-cued rhythms for all metabolites except serum cholesterol were observed when the lean rats were meal-fed. These data suggest that the rhythms of the ad libitum-fed obese rats may not be similar to those observed in the lean rat. Yet, changing the feeding schedule may be important in establishing rhythm patterns that will alter the anabolic profile characteristic of the Zucker obese rat.

ATP Citrate (pro-S)-Lyase↗

Effect of treadmill training on muscle oxidative capacity and accretion in young male obese and nonobese Zucker rats.

This study was designed to determine if treadmill training of the male obese Zucker rat could reverse its deficit in muscle accretion, expose a possible latent defect in its muscle oxidative capacity or significantly alter its food intake and lipid deposition. At 12 wk of age muscle mass and myofibrillar protein concentration were significantly lower and body lipid and food intake were significantly higher in the sedentary obese than in the nonobese rat. Exercise, by both inducing hypophagia and increasing energy output, led to a lower body weight, body lipid, and muscle mass in the exercised than in the nonexercised rats. This response to exercise did not differ between both phenotypes, except for body lipid. In that case the reduction of body lipid was greater for the obese rats. Muscle mitochondrial enzyme activities and rates of mitochondrial respiration in the obese rats were not different or greater than those of their sedentary or pair-exercised nonobese counterparts. Taken together these data indicate that oxidative capacity per unit of muscle is not significantly lower in the obese rats than in nonobese rats in both sedentary and exercised states, but that total muscle oxidative capacity is lower on a whole-animal basis since total muscle mass is lower. Further, exercise reduces, but does not prevent the enhanced weight gain and lipid accretion that characterizes the obese rat.

Animals↗

Oxygen consumption and oxidative capacity of hepatocytes from young male obese and nonobese Zucker rats.

The contribution of the liver to the increased metabolic efficiency of the obese rat (fa/fa) was examined. Oxygen consumption of isolated hepatocytes and isolated mitochondria, and hepatic activities of mitochondrial enzymes were measured. Hepatocyte oxygen consumption was similar in the obese and nonobese rats for all substrates tested. Mitochondrial respiration also was similar in both phenotypes for all substrates tested. Activities of citrate synthase, succinate dehydrogenase, and cytochrome oxidase were similar for obese and nonobese rats. Taken together, these data show that in vitro hepatic oxygen consumption and oxidative capacity are similar in obese and nonobese rats. Rates of mitochondrial respiration with palmitoylcarnitine further show that the capacity for hepatic lipid oxidation is similar in obese and nonobese rats. Therefore, the increased metabolic efficiency of the obese rat probably cannot be attributed to an intrinsic decreased hepatic oxidative capacity. Further, there is no defect in hepatic lipid oxidative capacity in the young obese rat.

Animals↗

Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles.

The nonsteroidal anti-inflammatory drug, flurbiprofen, a potent cyclooxygenase inhibitor, significantly decreases the resorption of alveolar bone in naturally occurring chronic destructive periodontal disease in beagles. This observation indicates that arachidonic acid metabolites are important in the alveolar bone loss of periodontitis and suggests a use for flurbiprofen in the management of bone resorption disease.

Alveolar Process↗

Nuclear medicine. An indicator of "active" alveolar bone loss in beagle dogs treated with nonsteroidal anti-inflammatory drug.

Nuclear medicine was used to assess the activity of alveolar bone loss in beagle dogs treated with the nonsteroidal anti-inflammatory drug flurbiprofen. Radiographic measurements of the rate of bone loss were taken during a 6-month "pretreatment" period and a 9-month treatment period. During the treatment period six dogs received a placebo, and six dogs received orally 0.02 mg/kg flurbiprofen daily for 9 months. In addition, each dog received periodontal surgery in one half of the mouth at the end of the pretreatment period. The rate of alveolar bone loss was significantly decreased in the treatment period in the flurbiprofen-treated dogs (P less than 0.001). Measurements of bone-seeking radiopharmaceutical uptake were taken 3 months after the initiation of therapy. The single measurement of uptake was compared to the rate of bone loss determined from repeated radiographs taken during the 9-month treatment period. Bone-seeking radiopharmaceutical uptake was an accurate indicator of "active" bone loss in 83.5% of the teeth studied.

Alveolar Process↗

Direct effect of triiodothyronine on glucose utilization in adipocytes from obese and nonobese Zucker rats.

The direct effects of L-T3 (triiodothyronine) on glucose utilization, 2-deoxyglucose uptake and O2 consumption were evaluated in vitro in isolated adipocytes from 6-week-old obese and nonobese Zucker rats. Adipocytes treated for 30 min with L-T3 had a 20-25% decrease in glucose conversion to CO2, fatty acids and glyceride-glycerol and uptake of 2-deoxyglucose. Incubation of adipocytes with either D-T3 or rT3 (reverse T3) did not decrease utilization of glucose. T3 also decreased the insulin-stimulated fatty acid synthesis from glucose in both obese and nonobese adipocytes. Adipocyte O2 consumption was decreased by T3 in media that contained glucose but not in media that contained either acetate or no exogenous substrate. These data indicate that T3 has a direct, immediate and specific action on adipocyte glucose utilization and may act to modulate adipose lipogenesis and lipolysis.

Adipose Tissue↗