Weight-matched Groups Research Articles

Ethnic Differences in Obesity and Surgical Weight Loss between African-American and Caucasian Females

In the general population, African-American females are more obese and resistant to weight loss than Caucasian women. In the present study, we examined the severity of obesity among morbidly obese African-American and Caucasian females, studied the effectiveness of Roux-en-Y gastric bypass (RYGBP), and sought to identify factors contributing to obesity and weight loss. The study population included 153 morbidly obese females randomly selected from our general bariatric patient population. Anthropometric measurements consisted of body weight, body mass index (BMI), excess weight, and waist, hip, thigh, and neck circumferences. Factors that may contribute to obesity included age, age of obesity onset, number of childbirths, calorie intake, diet composition, and degree of psychological distress. The effects of RYBGP were studied in weight-matched groups of African-American and Caucasian females (n=37 per group) at weight loss nadir, i.e. 12 to 18 months after surgery. We found that morbid obesity is more severe among African-American than Caucasian females. The greater degree of obesity of African-American, as compared to Caucasian, females is not due to ethnic differences in calorie intake, diet composition, age or age of obesity onset, number of childbirths, and psychological distress. RYGBP is less effective in reducing body fat and, consequently, excess body weight of the African-American than the Caucasian females, suggesting possible ethnic differences in fat metabolism. African-American females with morbid obesity have greater adiposity than do Caucasian women and lose significantly less body fat after RYGBP.

Endocrine Disruption and Flame-Retardant Chemicals: PBDE-99 Effects on Rat Sexual Development

Chemical flame retardants containing polybrominated diphenyl ethers (PBDEs) have attracted growing attention in recent years from toxicologists. Unlike their chemical cousins, dioxins and polychlorinated biphenyls (PCBs), environmental levels of PBDE compounds are increasing, as are concentrations found in human breast milk. This is of concern because of the potential that PBDEs may cause developmental toxicity due to endocrine-modulating effects, as has previously been documented with dioxins and PCBs. Results of a new German study examining developmental exposure in rats to a commonly used and environmentally abundant PBDE compound, PBDE-99, lend support to suspicions that PBDEs can have detrimental effects on sexual development in the offspring of exposed mothers [EHP 114:194–201]. The researchers examined sexual development end points—circulating sexual steroid concentrations, reproductive organ development, and sexually dimorphic behavior—that have been shown in similar rodent experiments to change following exposure to a mixture of PCBs reconstituted according to the congener pattern found in human breast milk. In the current study, weight-matched groups of dams received daily subcutaneous injections of PBDE-99 from gestational days 10 through 18 at doses of 1 or 10 milligrams per kilogram body weight (mg/kg). For comparison, another group was dosed with 30 mg/kg of the PCB mixture Aroclor 1254 (A1254). In PBDE-exposed male offspring, pronounced decreases in circulating sex steroids (estradiol, testosterone) were seen both at weaning and in adulthood. Anogenital distance, an androgen-dependent marker of sexual development, was also reduced in the male offspring. The males further displayed a dose-dependent increased preference for sweets, which is a sexually dimorphic behavior in rodents—this finding indicates feminization in the males. A slight acceleration in onset of puberty was noted in the low-dose group. The PBDE-exposed females had less severe effects. Onset of puberty was mildly delayed in the high-dose group. Also, the number of primordial/primary (rudimentary) ovarian follicles was reduced in the low-dose group, with a more pronounced decline in secondary (more developed) follicles within the high-dose group. These results could indicate an impaired reproductive life span, in that ovarian follicles are a key indicator of ovarian health. The females also had an insignificant increase in sweet preference. The researchers found no effect on sweet preference in male or female offspring exposed to the PCB mixture, but in the females they did see a significant increase in the number of tertiary (still larger, more developed) follicles. The exposure also adversely affected steroid concentrations in males and sexual development in both sexes. Thus, it appears that the pattern of endocrine-disruptive effects differs for PBDE-99 and A1254, which may be due to the higher content of dioxin-like compounds in the PCB mixture. The scientists also examined organ weights as an indicator of overall development in the rodents. They found that pituitary gland weights were slightly decreased in males in the PBDE-99 high-dose group at weaning, while they were increased in females in the low-dose group. The authors speculate that these effects may indicate a biphasic response to PBDE-99, and suggest that the phenomenon should be studied further in future research. Results also included a marked dose-dependent decrease in thyroid gland weight in adult rats of both sexes exposed to either PBDE-99 or A1254. This study adds to a growing body of literature indicating that chemical flame retardants are endocrine-disrupting compounds with the potential to profoundly affect sexual development and sexually dimorphic behaviors. The fact that several effects were seen in adulthood, long after termination of the exposure, indicates that the rats’ gestational exposure caused permanent physiologic damage. With increases in human body burden and environmental levels, and with the compounds’ apparent persistence in both venues, it is safe to assume that PBDEs will be the focus of more urgent research activity.

Echocardiographic Assessment of the Left Ventricular Outflow Tract in the Boxer

Soft, variable ejection murmurs are common in Boxers and are associated with increased left ventricular outflow tract (LVOT) ejection velocities. Whether these murmurs are physiologic or indicate mild aortic stenosis is controversial. Ejection velocity is impacted by LVOT area and ventricular stroke volume (SV), suggesting that these variables are pertinent to murmur development. Boxers with ejection murmurs have a smaller LVOT and equivalent SV indices, compared with values in dogs without murmurs. Three age- and weight-matched groups of dogs--15 Boxers with soft ejection murmurs (group I); 15 Boxers without murmurs (group II); and 15 nonBoxer dogs without murmurs (group III)--were studied. All dogs underwent 2-dimensional and Doppler echocardiographic examinations. The LVOT size at multiple levels; LVOT ejection velocity, stroke distance, and SV index; and right ventricular SV index were determined and compared by analysis of variance. Indexed LVOT areas in Boxer groups were not different, but were significantly smaller than those of non-Boxer dogs. Ejection velocities and stroke distances were significantly different across all groups, with group I having the highest and group III having the lowest values. Doppler SV indices (ml/m2) for group-I versus group-II Boxers were 70 +/- 16(SD) versus 62 +/- 12 for the LVOT (P = .27) and 58 +/- 12 versus 48 +/- 9 for the right ventricle (P = .14). These data suggest that a relatively smaller LVOT in Boxers predisposes them to increased ejection velocity and development of murmurs. The contribution of SV to the genesis of these often labile murmurs requires additional study.

Bone development: The effect of short-term alpha-ketoglutarate administration on long-term mechanical properties of ribs in ram lambs

The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram lambs were randomly assigned to two weight-matched groups at birth. During the first 14 days of life AKG was administered orally to the experimental group ( n = 12) at the dosage of 0.1 g/kg body weight per day, while the control group ( n = 11) received an equal dose of the vehicle. Lambs were slaughtered at 146 days of life and five left and right ribs (fourth to eighth) were removed for analysis. The influence of AKG on skeletal system development was evaluated in relation to both geometrical and mechanical properties, as well as quantitative computed tomography (QCT). No significant differences between the groups were recorded in terms of: (1) growth rate, (2) body weight at days 14, 28 and 130 of age or (3) final body weight. The weight and length of ribs were, however, significantly increased in the lambs given AKG for the first 14 days of neonatal life by 8.2% and 3.2%, respectively ( P < 0.01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% ( P < 0.01) and improved the mechanical endurance of ribs in terms of the moments of maximum elastic strength and ultimate strength by 10% and 8%, respectively ( P < 0.05). It could be concluded that AKG has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development and function of the skeleton during growth and later life.

Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations

To determine the effects of treating canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), calcium and phosphate concentrations in dogs. Serum calcium, phosphate and PTH concentrations were analysed in 22 dogs with HAC before treatment with trilostane and at a median of 210 days after commencing treatment. Pretreatment data were compared with data from an age- and weight-matched group of hospitalised patients, and post-treatment data were compared with pretreatment data. PTH and phosphate concentrations were significantly higher in dogs with HAC compared with control dogs. PTH concentrations reduced significantly with treatment, such that there was no longer a difference between the HAC and control groups. Phosphate concentrations also reduced significantly with treatment but there was still a significant difference between those in dogs with HAC and control dogs. Despite no significant difference between calcium concentrations in the pretreatment HAC and control groups, calcium concentrations increased significantly with treatment. These results show that adrenal secondary hyperparathyroidism resolves with treatment and suggest that increased calcium and phosphate levels have a role in its pathogenesis.

Hyperparathyroidism in dogs with hyperadrenocorticism

To assess the effect of canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), phosphate and calcium concentrations. PTH concentrations and routine biochemical parameters were measured in 68 dogs with HAC. Ionised calcium was measured in 28 of these dogs. The results obtained were compared with an age- and weight-matched group of 20 hospital patients that did not show signs of HAC. There were significant differences between the PTH, phosphate, alkaline phosphatase, creatinine and albumin concentrations between the two groups. Total and ionised calcium concentrations were not significantly different. Most of the dogs (92 per cent) with HAC had PTH concentrations that were greater than the reference range (10 to 60 pg/ml), and in 23 dogs they were greater than 180 pg/ml. There were significant positive correlations between the PTH and basal cortisol, post-adrenocorticotropic hormone (ACTH) cortisol and alkaline phosphatase concentrations, and also the phosphate and post-ACTH cortisol concentrations. Adrenal secondary hyperparathyroidism is a cause of increased PTH concentrations and may be associated with abnormalities in calcium and phosphate metabolism in dogs with HAC. The findings of this study could explain why canine HAC may cause clinical signs such as calcinosis cutis that are associated with altered calcium metabolism.

Hypothalamic Energy Balance Gene Responses in the Sprague‐Dawley Rat to Supplementation of High‐Energy Diet with Liquid Ensure and Subsequent Transfer to Chow

Energy dense, high fat, high sugar, foods and beverages in our diet are a major contributor to the escalating global obesity problem. Here, we examine the physiological and neuroendocrine effects of feeding rats a solid high-energy (HE) diet with or without a liquid supplement (Ensure) and the consequence of subsequently transferring animals back to chow (C). Outbred Sprague-Dawley rats were fed C until 49-56 days of age, and then transferred a HE diet for 3 weeks before allocation to one of two weight-matched groups. Over the next 10 weeks, one group remained on HE diet, whereas the other had access to the liquid diet, chocolate Ensure (EN), in addition to HE diet (HE + EN). Half the rats from each group were then killed, and the remainder were returned to C for 3 weeks. Supplementation of the HE diet with EN accelerated weight gain and increased daily energy intake, adipose tissue mass, and circulating leptin levels. Transferring animals back to C caused a decrease in bodyweight in the HE + EN group, whereas HE animals were weight stable. Both groups also exhibited voluntary hypophagia, although the magnitude and duration of this response was greater in HE + EN animals. The only effect of Ensure on the hypothalamic genes studied was on tyrosine kinase B expression in the ventromedial hypothalamic nucleus (VMH), which was increased in rats given the supplement. Withdrawal of the obesogenic diets decreased gene expression for cocaine-and-amphetamine regulated transcript (CART) and dynorphin (DYN) in the arcuate nucleus (ARC), and DYN and brain-derived neurotrophic factor (BDNF) in the VMH, whereas neuropeptide Y (NPY) gene expression in the ARC was increased. These changes were independent of previous dietary history. EN supplementation generates distinct physiological responses, yet has a minimal effect on hypothalamic neuropeptide or receptor gene expression, possibly due to the development of leptin resistance. Withdrawal of obesogenic diets induces changes in the gene expression consistent with NPY, CART and BDNF attempting to oppose weight gain on either HE or HE + EN.

Influence of flavomycin on microbial numbers, microbial metabolism and gut tissue protein turnover in the digestive tract of sheep

Flavomycin is an antibiotic that promotes growth in ruminant and non-ruminant livestock. The aim of this study was to determine the mechanism of action of flavomycin in sheep by measuring microbial numbers, microbial metabolism and gut tissue protein turnover at different sites in the digestive tract. Two weight-matched groups (n 5) of male castrate lambs (30 kg) received 800 g grass cubes/d for 6 weeks, with one group receiving 20 mg/d flavomycin during the last 2 weeks. Samples of digesta and gut tissue segments were obtained immediately post mortem, 90 min after a flood-dose of [ring-D5]phenylalanine. Viable bacterial counts and volatile fatty acid concentrations were highest in ruminal digesta, followed by the colon and caecum, then the duodenum and ileum. The only effect of flavomycin was an increased bacterial count in the rumen (3.5 v. 1.2 x 10(9) per g; P=0.04). Acetate was proportionally greater and propionate and butyrate were lower in the caecum and colon than the rumen. Flavomycin had no effect on volatile fatty acid proportions or ammonia concentrations. Bacteria growing on peptides as sole C source were not affected by flavomycin. Proteolytic, peptidolytic and amino acid deamination activities were similar in the rumen, caecum and colon; they tended to be lower in animals receiving flavomycin. Protein turnover in ruminal wall and duodenal tissues, measured by a flood-dose technique, decreased with flavomycin (P=0.075 and 0.027, respectively). Thus, flavomycin differs from ionophores in its mode of action. It may influence protein metabolism of both digesta and tissue throughout the ruminant digestive tract.

Long-term denervation of the humerus in turkeys as an experimental model for osteopenia

The aim of this study was to evaluate the influence of long-term denervation on volumetric bone mineral density, and geometrical and mechanical properties of the humerus in turkeys. The experiment was conducted from d 22 after hatching until wk 17 of life. All experimental birds (male turkeys) were randomly divided into 2 weight-matched groups. The first group of turkeys served as the control group and underwent a sham operation on the right wing, and the second group was subjected to surgical denervation of the right humerus. The denervation was performed by neurectomy of the radialis and the mediano-ulnaris nerves in the region of the proximal epiphysis of the humerus. All the left wings within both groups were surgically untouched. The left humerus served as the control bone to the right humerus in both investigated groups. Effect of denervation of humerus was determined in terms of geometrical and mechanical properties and quantitative computed tomography. The denervation of the humerus in turkeys significantly decreased volumetric bone mineral density, and geometrical and mechanical properties of this bone, when compared with the results obtained in humerus from the sham-operated or surgically untouched wings. However, no significant differences between right and left humerus were observed when analyzing all of the investigated parameters in the sham-operated group of turkeys. It is concluded that long-term denervation of humerus in turkeys induces osteopenia and may serve as a new experimental model for investigating factors that affect skeletal homeostasis in poultry and other vertebrates.

Training to yoga respiration selectively increases respiratory sensation in healthy man

Because yoga practitioners think they are benefiting from their breath training we hypothesized that yoga respiration training (YRT) could modify the respiratory sensation. Yoga respiration (YR) ("ujjai") consisted of very slow, deep breaths (2-3 min(-1)) with sustained breath-hold after each inspiration and expiration. At inclusion in the study and after a 2-month YRT program, we determined in healthy subjects their eupneic ventilatory pattern and their capacity to discriminate external inspiratory resistive loads (respiratory sensation), digital tactile mechanical pressures (somesthetic sensation) and sound-pressure stimulations (auditory sensation). Data were compared to a gender-, age-, and weight-matched control group of healthy subjects who did not undergo the YRT program but were explored at the same epochs. After the 2-month YRT program, the respiratory sensation increased. Thus, both the exponent of the Steven's power law (Psi=kPhin) and the slope of the linear-linear plot between Psi and mouth pressure (Pm) were significantly higher, and the intercept with ordinate axis of the Psi versus Pm relationship was lower. After YRT, the peak Pm developed against inspiratory loads was significantly lower, reducing the load-induced activation of respiratory afferents. YRT induced long-lasting modifications of the ventilatory pattern with a significant lengthening of expiratory duration and a modest tidal volume increase. No significant changes in somesthetic and auditory sensations were noted. In the control group, the respiratory sensation was not modified during a 15-min period of yoga respiration, despite the peak Pm changes in response to added loads were then significantly reduced. These data suggest that training to yoga respiration selectively increases the respiratory sensation, perhaps through its persistent conditioning of the breathing pattern.

Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins.

Human adenovirus Ad-36 induces adiposity and lowers total serum cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated with human obesity. We examined the early effects of Ad-36 inoculation on plasma cholesterol levels in hamsters fed a hyperlipidemic diet. A total of 32 male Golden Syrian hamsters were divided into two equal weight-matched groups and intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In each group, the animals were fed either a purified diet (PF, n=8) 40%en fat +/-194 mg cholesterol/1000 kcal or chow (C, n=8) ad libitum. Animals were killed 5 weeks postinoculation. Nested PCR assay detected Ad-36 DNA in the lung, liver, visceral adipose tissue and skeletal muscle of the INF group, but not in the CON animals. Ad-36 antibodies were detected in the INF group only. For all animals, total plasma cholesterol (TC) was not significantly affected by Ad-36 treatment (203+/-92 vs 193+/-75 mg/dl, P=NS; INF vs CON, respectively). In 5 weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow (128+/-39 vs 130+/-27 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269+/-70 vs 256+/-47 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins isolated by density gradient ultracentrifugation showed a greater proportion of LDL cholesterol in INF animals, as compared to CON (28.4+/-1.6% vs 16.4+/-1.2%, P=0.02), regardless of dietary treatment (INF-P vs CON-P: 27.3+/-2.1 vs 15.7+/-1.5%, P=0.07; and INF-C vs CON-C: 29.4+/-1.2 vs 17.0+/-1.1%, P=0.009). This shift appears to be from HDL cholesterol to the LDL fractions. These data suggest that in the hamster (a model resembling several aspects of human lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular processing of lipoproteins resulting in a more atherogenic lipoprotein profile.

Tissue mineralization is increased following 1-year treatment with high doses of bisphosphonates in dogs

Suppression of bone turnover using anti-resorptive agents such as bisphosphonates prevents bone loss but also may increase tissue mineralization. This may make the bone more prone to initiate microcracks. The objective of this study was to determine whether suppression of remodeling caused by treatment of dogs for 1 year with five times the clinical dose of either alendronate or risedronate is associated with increased tissue mineralization and whether it changes the nature of the mineral crystal. Thirty-five dogs were divided into three weight-matched groups and treated daily for 1 year with a subcutaneous injection of saline (CON, n = 12), oral risedronate (RIS, 0.5 mg/kg/day, n = 11), or oral alendronate (ALN, 1.0 mg/kg/day, n = 12). Density fractionation, peripheral quantitative computerized tomography (pQCT), and quantitative backscattered electron microscopy (qBSE) were used to evaluate changes in mineral content of bone tissue from the vertebrae or ribs. Infrared microspectroscopy (IR) and X-ray diffraction were used to assess the quality of the mineral and some aspects of collagen structure in the thoracic vertebrae and iliac crest. Following 12 months of treatment, there was a significant shift toward higher density bone in both ALN ( P = 0.04) and RIS ( P = 0.002) by density fractionation methods. IR, pQCT, and qBSE did not detect any significant differences in mineralization, probably because of their lower sensitivity and/or because of the smaller region of interest they sample. No significant differences were found in the maturity of the mineral crystals or in their length or size. We conclude that treatment for 1 year with high doses of bisphosphonates which suppress bone remodeling up to 90% increases tissue mineralization, but does not change the nature of the mineral crystal.

Evidence for an extensive collagen type III proximal domain in the rat femur: II. Expansion with exercise

Exercise in youth may affect bone “quality” as well as quantity. Using the rat model, 1.5-month-old females were divided into four weight-matched groups, exercised short-term (6 weeks, E s, n = 20) and long-term (14 weeks, E L, n = 10) by access to monitored running wheels, and corresponding “sedentary” controls (S S short-term, n = 20; S L long-term, n = 10). Femora were either plastic-embedded or fresh-frozen. Transverse histological slices, 100 μm thick, were cut midshaft, while similar cryosections, 8 μm thick, were prepared from the same site and also coronal to the femoral neck region. An image analyser measured femoral neck and midshaft microarchitecture, while immunostaining localized collagen type III-rich fibres (CIII, an index of Sharpey fibre insertions) and osteopontin-rich osteons (OPN, an index of remodelling). Exercise increased cortical bone (proximal width +18%, midshaft area +7%). It also raised cancellous bone volume (+25%) by trabecular thickening (+30%) with more intraosseous vascularity and new trabecular interconnections (node-terminus ratio, +57%; trabecular pattern factor, −147%; marrow star volume. −48%). In the cortex a prominent discrete subperiosteal domain became wider (+50% midshaft) with exercise and contained more numerous (+15%) CIII-stained fibres. In contrast the encircled inner bone developed more numerous (+14%) OPN-rich osteons. It is concluded that short-term voluntary exercise augments both cortical and cancellous microarchitecture. It also alters protein composition, such that expanding arrays of Sharpey’s fibres within a circumferential proximal domain (Part I) interconnect more powerfully with the musculature and interface more robustly with the core bone that in response becomes more vascular and biodynamic, providing further insight into how muscle mass may be skeletally translated.

Adrenal gland volume after spinal cord injury.

Spinal cord injury in adult men may result in hypothalamic-pituitary-adrenal axis dysfunction. Atrophy of adrenal glands was speculated in these patients. This study was undertaken to clarify the functional-anatomic correlation between adrenal volume and body surface area in subjects with spinal cord injury with impaired adrenal reserve. Twenty male subjects with chronic spinal cord injury with impaired adrenal reserve were identified by adrenocorticotropic hormone stimulation test from a group of 42 subjects. All subjects with spinal cord injury and healthy volunteers underwent computed tomographic imaging with contiguous 3-mm section over adrenal glands for volumetric measurements. Ten pairs of subjects with spinal cord injury and controls with matched height and weight were included in the statistical analysis. Significantly increased relative adrenal volumes were noted among subjects with chronic spinal cord injury and impaired adrenal reserve as compared with the body weight-matched and height-matched control group. Increased relative adrenal volumes were found after chronic spinal cord injury. Hyperplasia of the zona glomerulosa may be the cause of increased relative adrenal volume after chronic spinal cord injury.

Increased Oxidative Damage in Vitamin C Deficiency is Accompanied by Induction of Ascorbic Acid Recycling Capacity in Young But Not Mature Guinea Pigs

Ascorbic acid (AA) recycling, i.e. the intracellular regeneration of AA from its oxidized forms semidehydroascorbyl radical and dehydroascorbic acid (DHA), presumably has a key function in maintaining redox homeostasis. Like humans, guinea pigs cannot synthesize AA. In the present paper, the effects of severe AA deficiency on the AA recycling capacity in erythrocytes (RBCs) and liver homogenates were studied in young and mature guinea pigs. Twelve animals of each age category were divided into weight-matched groups of six animals and fed either an AA deficient or sufficient diet. After 5 weeks, they were sacrificed and RBC and liver ascorbate recycling was estimated along with glutathione, tocopherols, AA, SOD, and malondialdehyde (MDA). For young animals, AA recycling capacity was significantly increased in RBCs from the deficient group as compared to the controls ( p <0.001). RBC MDA was not increased by incubation with t -butylhydroperoxide (TBH) while the initial MDA level was significantly elevated ( p <0.001). In mature animals, neither RBC recycling nor MDA levels depended on AA status. Liver recycling capacity was not affected by age or diet, while liver MDA was significantly higher in young but not in mature deficient animals compared to respective controls ( p <0.01). In young animals, incubation with TBH resulted in significant MDA formation in the deficient compared to sufficient animals in both liver and RBCs ( p <0.05). RBC glutathione was not significantly changed by age or diet indicating that the observed changes in recycling capacity are enzyme dependent. The results suggest that young guinea pigs may have a more adaptable antioxidant defense system compared to mature animals while also being more susceptible to oxidative stress.

Relationship of insulin sensitivity and ApoB levels to intra-abdominal fat in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is one of the most common familial dyslipidemias associated with premature heart disease. Subjects with FCHL typically have elevated apolipoprotein B (apoB) levels, variable elevations in cholesterol and/or triglycerides, and a predominance of small, dense, low density lipoprotein particles. It is thought that insulin resistance is important in the expression of the combined hyperlipidemia phenotype. To further characterize the relationship between insulin resistance and increased apoB levels, 11 subjects from well-characterized FCHL families and normal control subjects matched for weight and/or age underwent measurement of intra-abdominal fat (IAF) and subcutaneous fat (SQF) by CT scan, insulin sensitivity (Si) by the frequently sampled intravenous glucose tolerance test, and lipoprotein levels. Body mass index and IAF were higher and Si was lower (more insulin resistant) in the FCHL group than in the age-matched group, but the values were similar in the FCHL group and the age- and weight-matched control group. When the relationship between body fat distribution and Si was tested with multiple linear regression, only IAF was significantly correlated with Si after the addition of SQF and body mass index as independent variables. For any level of insulin sensitivity or IAF, however, apoB levels remained higher in the FCHL subjects than in the control groups. In conclusion, in FCHL, visceral obesity is an important determinant of insulin resistance. Visceral obesity and insulin resistance, however, do not fully account for the elevated levels of apoB in this disorder, and this study provides physiological support for separate, but additive, genetic determinants in the etiology of the lipid phenotype.

Evidence for long-term pancreatic damage caused by laxative abuse in subjects recovered from anorexia nervosa.

This study examined whether a prior history of laxative abuse results in long-term changes in gastrointestinal function. The functioning of the enteroinsular axis was examined by measuring the insulin response to a standard meal. The study involved 18 subjects who had fully recovered from anorexia nervosa (AN) and an age and weight-matched control group. In the recovered group, 10 of 18 subjects had a history of laxative abuse. Subjects with a prior history of laxative abuse show a more gradual increase and decrease in insulin secretion, but no differences in glucose response or hunger ratings. Because there are no differences in the glucose response to the meal, it is hypothesized that the difference in insulin response is due to changes in the enteroinsular axis. These data indicate that chronic laxative abuse induces long-term changes in gastrointestinal function.

Abnormalities in muscle function during gait in relation to the level of lumbar disc herniation.

A comparison between gait in patients undergoing surgery for L4 and L5 lumbar disc herniations and that in an age- and weight-matched control group. To study whether changes in the moments produced at the ankle and knee joints during walking reflect the neurologic level of a herniated nucleus pulposus. Lumbar herniated discs often cause muscle weakness, reduced motor function, and change in walking capacity. The specific effects of a disc herniation on muscle function during gait is poorly documented. Conventional physical examination and kinetic analysis of gait were performed on 16 patients who subsequently underwent surgery for herniated discs (eight with L4-L5 and eight with L5-S1 disc herniations) and 16 healthy control subjects. The three components of the external moment at the ankle and knee were computed. The peak magnitudes of specific components of the external moments were compared with those of the control group. Reduced external ankle plantar flexion moment, indicating a decreased function of the ankle dorsiflexors, was found in patients with herniated nucleus pulposus of both L4-L5 and L5-S1. Reduced external ankle dorsiflexion moment, indicating a decreased function of the ankle plantar flexors, was found only in patients with a lesion to the L5-S1 disc, but not in those with herniations at L4-L5. Preoperative gait analysis identified functional deficits of the muscles about the ankle and foot that relate to the level of the herniation. Kinetic measurements can assist in understanding the functional limitations associated with specific levels of a herniation.

Effects of ethanol on offspring of C57BL/6J mice alcoholized during gestation

The effects of chronic alcohol consumption during pregnancy were analysed in the gestation and offspring of alcoholized mice. Female C57BL/6J mice were placed overnight with stud males and the presence of a sperm plug in the next morning indicated the onset of gestation. Pregnant mice were distributed in two weight-matched groups. In the alcoholized group, the mice received a high protein liquid diet ad libitum containing 27.5% of ethanol-derived calories (5.28% v/v) from gestation day 5 to 19. The control group received the same volume of diet containing isocaloric amounts of maltose-dextrin substituted for ethanol. After postnatal day zero, the dams received food pellets and tap water ad libitum. On postnatal day 6 the pups were counted and weighed at variable intervals up to the 60th day of life. The majority of the pregnant dams that have received ethanol completed the gestational period, and the chronic consumption of alcohol did not interfere with the number of dams that gave birth. The alcoholized and control dams gained an equivalent weight and consumed an equivalent volume of diet throughout the gestation. The number of pups from alcohol diet dams was 46,26% smaller compared with the control group. There were less male than female pups in the offspring of alcoholized mice. Teratogeny like gastroschisis and limb malformation were present in the offspring of alcoholized dams. The body weight of the offspring of alcoholized mice increased from the 18th to the 36th postnatal day.

Trabecular bone turnover and bone marrow cell development in tail-suspended mice.

To clarify the relationship between the changes of trabecular bone turnover and bone marrow cell development during mechanical unloading and reloading, we performed experiments with tail-suspended mice. At 8 weeks of age, 150 male ddY mice were divided into three body weight-matched groups. Mice of group 1 were euthanized at the start of tail suspension (day 0) as a baseline control. The mice of group 2 were subjected to hindlimb unloading by tail suspension for 14 days and reloading for the subsequent 14 days. The mice of group 3 were normally loaded as age-matched controls. Mice of groups 2 and 3 were sacrificed at 7, 14, and 28 days after the start of the experiment. In the first experiment (histomorphometric study of tibiae), unloading for 7 and 14 days and reloading for the subsequent 14 days significantly decreased the bone volume compared with that in the age-matched controls, respectively. Unloading for 7 and 14 days also significantly reduced the bone formation rate (BFR/BS), respectively, but reloading for the subsequent 14 days restored BFR/BS to the control level. While the unloading for 7 and 14 days significantly increased both the osteoclast surface (Oc.S/BS) and the osteoclast number (Oc.N/BS), the reloading for the subsequent 14 days decreased Oc.S/BS and Oc. N/BS, respectively. In the second experiment (bone marrow cell culture study of tibiae), unloading for 7 and 14 days reduced the adherent stromal cell number, without significance. Unloading for 7 days significantly decreased the mineralized nodule formation. Reloading for the subsequent 14 days markedly increased the adherent stromal cell number and the mineralized nodule formation. Unloading for 7 days significantly increased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. These data clearly demonstrate that unloading reduces bone formation and increases bone resorption, and subsequent reloading restores reduced bone formation and suppresses increased bone resorption, closely associated with the changes in adherent stromal cell number, mineralized nodule formation, and the number of TRAP-positive multinucleated cells.