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Biomedical subjects

L Shackelford

Publications and source records attributed to L Shackelford.

13 recordsLinked to original sources

Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats.

Flax seed oil and flax seed meal are good sources of omega-3 fatty acids. The objective of this study was to explicate the effects of feeding flax seed oil and flax seed meal on AOM-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Following an acclimatization period, rats were divided into six groups and fed AIN 93G diet Control (C), C+7 and 14% soybean oil (SBO), C+7 and 14% flax seed oil (FSO) and C+10 and 20% flax seed meal (FSM). All rats received 16 mg/kg body weight of AOM at 7 and 8 weeks of age. The rats were euthanized with CO2 at 17 weeks of age. FSM and FSO reduced the incidence of ACF which are putative precursor lesions in the development of colon cancer in the distal colon by 88% and 77%, in the proximal colon by 86% and 87% with a total reduction of 87.5% and 84%, respectively. Glutathione-S-transferase (GST) activities were significantly (P<0.05) higher in rats fed C+7 and 14% FSO and C+10 and 20% FSM, as compared to rats fed C+SBO diets. Results of this study showed that FSO and FSM reduced the incidence of AOM-induced ACF formation and may therefore be effective chemopreventive agents.

Animals↗

Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Red palm oil (RPO) contains significant levels of carotenoids and Vitamin E. In this experiment we compared the inhibitory effects of RPO (7% and 14% levels) and soybean oil (7% and 14%) on azoxymethane (AOM) induced aberrant crypt foci (ACF). Thirty-two male Fisher 344 rats were randomly assigned to four groups. Two groups received AIN-93 G control (C) diet containing 7% and 14% soybean oil (SBO), respectively. Groups 3 and 4 received a treatment diet consisting of 7% and 14% RPO, respectively. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at 7 and 8 weeks of age. At 17 weeks of age rats were killed by CO(2) asphyxiation. Numbers of ACF (mean+/-SE) in the proximal and distal colon were: 39.9 +/- 0.9, 53.8 +/- 2.8, 26.0 +/- 3.0, 27.5 +/- 1.5 and 118.2 +/- 1.7, 125.6 +/- 3.2, 41 +/- 7, 52.3 +/- 1.8 in rats fed 7% SBO, 14% SBO, 7% RPO and 14% RPO, respectively. The results of this study showed that RPO reduced the incidence of AOM induced ACF and may therefore have a beneficial effect in reducing the incidence of colon cancer.

Animals↗

Monitoring sweat calcium using skin patches.

The purpose of this study was to determine whether a simple noninvasive sweat collection method using skin patches would be useful in monitoring sweat Ca and to determine changes in dermal Ca loss during a bed rest study testing a resistive exercise countermeasure. The study showed that the technique was highly reproducible: the mean intra-subject variation approached zero and the inter-individual variability (%CV) varied from 18% to 32% for the three anatomical regions (arm, chest, and back) tested. There was less than 10% difference in sweat Ca excretion from different skin regions within the same individual at a given time point. A calculated estimate of total body sweat excretion for 12 bed rest subjects was 35 +/- 4 mg/day (mean +/- SE), close to published whole body measurements. Bed rest testing showed no significant differences with or without exercise when conducted in a temperature-controlled environment. We conclude that the skin patch technique is useful for monitoring changes in sweat Ca.

Adult↗

Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats.

Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment 1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.

Age Factors↗

Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young Fisher 344 rats.

This study was designed to determine the effect of 10% dietary long-chain inulin on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF) and small intestinal and colon tumors at the initiation (I), promotion (P) and I + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin. All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7 wk of age followed by a second injection at 8 wk of age. An additional group of five rats received only saline and consumed the control diet. The rats received the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF experiment and 45 wk for the end-point tumor experiment. Feed intake, weight gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF compared with the control group. Tumor incidences in the small intestine and colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and 90, 73, 69 and 50%, respectively. The corresponding values for the distal portion of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor-bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups, respectively. All groups differed, P < 0.05. The results of this study indicate that dietary long-chain inulin suppresses AOM-induced ACF formation, an early preneoplastic marker of colon tumorigenesis in rats, and colon tumors, particularly at the promotion stage.

Age Factors↗

Muscle volume, MRI relaxation times (T2), and body composition after spaceflight.

Postflight changes in muscle volume, calf muscle transverse relaxation time, and total body composition were measured in 4 crewmembers after a 17-day mission and in 14-16 crewmembers in multiple shuttle/Mir missions of 16- to 28-wk duration. During the 17-day mission, all muscle regions except the hamstrings significantly decreased 3-10% compared with baseline. During the shuttle/Mir missions, there were significant decreases in muscle volume (5-17%) in all muscle groups except the neck. These changes, which reached a new steady state by 4 mo of flight or less, were reversed within 30-60 days after landing. Postflight swelling and elevation of calf muscle transverse relaxation time persisted for several weeks after flight, which suggests possible muscle damage. In contrast to the 17-day flight, in which loss in fat, but not lean body mass, was found (25), losses in bone mineral content and lean body mass, but not fat, were seen after the longer shuttle/Mir missions. The percent losses in total body lean body mass and bone mineral content were similar at approximately 3.4-3.5%, whereas the pelvis demonstrated the largest regional bone loss at 13%.

Adult↗

Bone mineral and lean tissue loss after long duration space flight.

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.

Journal Article↗

T2 vertebral bone marrow changes after space flight.

Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

Adult↗

Future human bone research in space.

Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

Animals↗

Bifidobacterium longum and lactulose suppress azoxymethane-induced colonic aberrant crypt foci in rats.

Bifidobacterium longum has been shown to afford protection against colon tumorigenesis. Lactulose, a keto analog of lactose, serves as a substrate for preferential growth of Bifidobacterium. It is not known whether feeding lactulose along with B. longum will have any advantage over feeding of B. longum alone. To test this combination effect, 61 male Fisher 344 weanling rats were divided into four groups of 15 rats each (16 in the control group) and assigned to one of the following four diets for 13 weeks: (i) AIN76A (control, C); (ii) C + 0.5% B. longum (C+Bl, containing 1 x 10(8) viable cells/g feed); (iii) C + 2.5% lactulose (C+L); (iv) C + 0.5% B. longum + 2.5% lactulose (C+Bl+L). All animals received a s.c. injection of azoxymethane at 16 mg/kg body wt at 7 and 8 weeks of age. Colons of 10 rats from each dietary group were analyzed for aberrant crypt foci (ACF), which are preneoplastic markers. Colonic mucosa and livers from five rats were analyzed for glutathione S-transferase (GST, a Phase II enzyme marker). Results indicate that feeding of lactulose and B. longum singly and in combination reduces the number of ACF (P = 0.0001) and the total number of aberrant crypts significantly (P = 0.0005). The total number of ACF in diets C, C+Bl, C+L and C+Bl+L were 187 +/- 9, 143 +/- 9, 145 +/- 11 and 97 +/- 11 respectively. There was no significant difference in weight gain among treatments. Colonic mucosal GST levels were significantly (P = 0.05) higher in the Bl and L groups compared with group C. Initially there was a mild diarrhea in lactulose-fed rats. There was a positive correlation between higher cecal pH and number of ACF. Results of the study indicate that Bifidobacterium and lactulose exert an additive antitumorigenic effect in rat colon.

Animal Feed↗

Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software.

This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.

Absorptiometry, Photon↗

Otological and habilitative management of children with Down syndrome.

It has been well-established that children with Down syndrome experience a high incidence of persistent conductive hearing loss because of their predisposition to stenosis of the external auditory canal (EAC), cerumen impaction, serous otitis media (SOM), and cholesteatoma. Because this hearing problem may be a primary cause of the spoken communication skills in these children being far below their cognitive ability, assertive management is required. The authors present an aggressive multi-discipline treatment model that is instituted during the first year of life in an infant with Down syndrome. Reconstruction of the EAC, amplification technology, and speech/language intervention that emphasizes auditory-verbal (A/V) therapy are discussed. In a pilot study, we compared the language development of six infants with Down syndrome who received aggressive treatment during their first year of life (group A) to six infants who did not (group B). The results showed age-appropriate oral language development for the infants in group A.

Child Development↗