Dynamics of nitrogen retention at two feeding levels in gestating parity 2 and 3 sows.

Parity-2 ( = 39) and -3 ( = 28; same sows from parity-2 sows) Yorkshire sows were used to measure whole body protein deposition (Pd) during gestation (maternal and pregnancy-associated) at 2 feeding levels to test the hypothesis that the pattern of whole body and maternal Pd during gestation does not differ when feeding either 15% above or 15% below estimated ME requirements, both exceeding AA requirements. Initial BW and backfat (BF) at d 26 ± 0.3 of gestation were 195.4 ± 5.2 kg and 15.1 ± 0.5 mm, and 223.1 ± 5.3 kg and 16.0 ± 0.6 mm for parity-2 and -3, respectively. Sows were assigned to 1 of 2 feeding levels (high and low; 15% above and 15% below estimated ME requirements, respectively) of the same diet (3.30 Mcal ME/kg, 17.8% CP, 0.82% SID Lys) from d 31 to 110 of each gestation cycle. Five N balances were conducted throughout each gestation starting at d 36, 51, 65, 85, and 106 ± 0.5 during 4-d periods. Pregnancy-associated Pd was model-derived for each sow and N balance period using the gestating sow model, based on actual litter size (including stillborn) and mean piglet birth weight. Maternal Pd was calculated as the difference between whole body and pregnancy-associated Pd. Whole body Pd and maternal Pd were greater ( 0.002) for sows on the high feeding level. Whole body Pd increased ( 0.001) with day of gestation and maternal Pd did not differ with day of gestation. Whole body and maternal Pd were greater ( ≤ 0.004) for parity-3 sows from d 51 to 54 and 85 to 88 of gestation only. Estimated efficiency of Lys retention for whole body Pd was not different between the 2 feeding levels, greater ( 0.016) for parity-3 sows, and increased quadratically ( 0.027) with day of gestation. During lactation (21.3 ± 0.3 d), there was no effect on sow ADFI and minimal effect on litter performance due to gestation feeding level or parity. Sows on the high feeding level had greater ( 0.009) BW and BF loss during lactation and these parameters were not affected by parity. Feeding 15% above estimated ME requirements during gestation resulted in consistently greater whole body and maternal. Whole body and maternal Pd were particularly greater for parity-3 sows from d 51 to 54 and 85 to 88 of gestation. The pattern of maternal Pd, regardless of feeding level, was not affected by day of gestation and is in contrast to , where maternal Pd is expected to be greater in early gestation.

Dynamics of nitrogen retention in gestating gilts at two feeding levels.

Whole-body protein deposition (Pd) is a main determinant of AA requirements of gestating gilts; however, data on the dynamics of Pd is limited. The main objective of this study was to measure whole-body Pd (pregnancy-associated and maternal) during gestation in gilts at 2 feeding levels. Changes in BW and backfat (BF) throughout gestation and subsequent lactation performance were also evaluated. We hypothesized that the effect of feed intake on maternal Pd decreases toward the end of gestation due to increased fetal nutrient demands. Fifty-one pregnant Yorkshire gilts (initial BW and BF at d 28 ± 0.5 of gestation were 168.6 ± 2.2 kg and 16.9 ± 0.8 mm, respectively) were used. Gilts were assigned to 1 of 2 feeding levels (high feeding level and low feeding level; 2.54 and 1.87 kg/d, respectively) of the same diet (3.30 Mcal ME/kg, 17.8% CP, 0.82% standard ileal digestible Lys) from d 33 to 112 ± 0.5 of gestation. Nitrogen balance observations (based on total urine collection with urinary catheters and determination of fecal N digestibility using an indigestible marker) were made at 5 distinct time periods, each 4 d in length, starting at d 38, 52, 66, 87, and 108 ± 0.5 of gestation. Pregnancy-associated Pd (fetus, mammary gland, uterus, and placenta and fluids) was calculated for each gilt and N balance period using the gestating sow model, based on actual litter size (including stillborns) and mean piglet birth weight. Maternal Pd was calculated as the difference between whole-body Pd and pregnancy-associated Pd. Across all N balance periods, whole-body and maternal Pd were consistently 40.1 ± 5.2 g/d greater ( < 0.001) for the high feeding level compared with the low feeding level. At both feeding levels, whole-body Pd increased (linear and quadratic, < 0.020) with day of gestation and maternal Pd decreased (cubic, < 0.010) with day of gestation. During lactation, maternal voluntary feed intake and litter performance were not affected by gestation feeding level. Gilts on the high feeding level lost more BW and BF during lactation ( ≤ 0.030). In summary, the effect of feeding level on whole-body and maternal Pd was constant throughout gestation. However, the gradual decline in maternal Pd with day of gestation is in contrast to that reported by the and has important implications for the factorial estimation of AA requirements of gestating gilts toward the end of gestation.

Investigations of positronium formation and destruction using 3gamma/2gammaannihilation-ratio measurements.

Positronium (Ps) produced by 4 to 40 eV positrons colliding with Ne, Ar, Kr, CO2, and O2 is investigated by measuring the ratio of signals of two gamma rays in coincidence resulting from (a) three gamma annihilation of ortho-Ps and (b) two annihilation gamma rays due to para-Ps decay and destruction of ortho-Ps at an aluminum scattering cell surface. These ratios provide evidence that relates to the kinetic energy dependence of ortho-Ps interactions with an aluminum surface, the Ps formation potential at this surface, and the fact that Ps is being formed with inner orbital electrons for CO2 and O2.

Differential inhibition of human cancer cell proliferation by citrus limonoids.

Limonoids have been shown to inhibit the growth of estrogen receptor-negative and -positive human breast cancer cells in culture. The primary objective of this study was to test the antiproliferative activity of limonoids (obacunone 17 beta-D-glucopyranoside, nomilinic acid 17 beta-D-glucopyranoside, limonin, nomilin, and a limonoid glucoside mixture), found in high concentrations in mandarin (Citrus reticulata Blanco), against a series of human cancer cell lines. The human cancer cell lines included leukemia (HL-60), ovary (SKOV-3), cervix (HeLa), stomach (NCI-SNU-1), liver (Hep G2), and breast (MCF-7). The growth-inhibitory effects of the four limonoids and the limonoid glucoside mixture against MCF-7 cells were significant, and the antiproliferative activity of the different citrus limonoids was also dose and time dependent. No significant effects were observed on growth of the other cancer cell lines treated with the four individual limonoids at 100 micrograms/ml. At 100 micrograms/ml, the limonoid glucoside mixture demonstrated a partial inhibitory effect on SKOV-3 cancer cells. With use of flow cytometry, it was found that all the limonoid samples could induce apoptosis in MCF-7 cells at relatively high concentrations (100 micrograms/ml). Considering the high concentration needed to induce apoptosis, it is unlikely that this is the primary mechanism of action for the cytotoxic effects seen with limonoids in this study. Further work is needed in this area to establish the mechanism of action of citrus limonoids on human breast cancer cells.

Preemptive pharmacologic intervention in radiation-induced salivary dysfunction.

Xerostomia ("dry mouth") is a symptom of several diseases. It also occurs as a side effect of certain therapeutic interventions, most frequently pharmacotherapy. The most severe and irreversible forms of salivary dysfunction result from damage to or loss of salivary acinar cells. One of the severest forms of iatrogenic salivary gland destruction results from the therapeutic doses of irradiation given to treat head and neck cancer or to purge the bone marrow before transplantation. Xerostomia encompasses a wide range of involvement, from an inconvenience when mild, to a debilitating condition when severe. Reports of the symptom of dry mouth by patients do not always correlate with the degree of diminished salivary flow. However, a significant loss of stimulated flow makes it difficult to process solid food into a bolus that can be swallowed. If sustained, nutritional deficiencies may result. Saliva also facilitates formation of speech patterns. Its loss hinders speaking and communicating, possibly causing the patient to withdraw from social interaction. Together these conditions can impair the physiological and psychological well-being of the patient. Thousands of individuals undergo radiation therapy for head and neck cancer in the United States each year. Increasing numbers are receiving total body radiation before transplantation of bone marrow. Although the salivary gland is not one of the more actively dividing organs in the body, nevertheless it ranks as one of the most radiosensitive. The mechanism of this sensitivity is not understood. This article reviews human and animal pathophysiology of radiation-induced salivary damage. We also discuss animal studies that have employed various strategies to modify and clarify this process. Finally, we describe encouraging results from early clinical trials suggesting that protection of salivary glands during therapeutic irradiation may be possible.

Development of a test battery to identify older drivers at risk for self-reported adverse driving events.

OBJECTIVES: The purposes of this study were (1) to develop a battery of tests that assessed a wide range of functional abilities relevant to driving yet could be performed in a clinician's office and (2) to determine which of these tests were most closely associated with self-reported adverse driving events. DESIGN: A cohort study. SETTING: An urban community. PARTICIPANTS: Participants were drawn from the Project Safety cohort, a probability sample of noninstitutionalized older persons in New Haven, Connecticut, initiated in 1989. The current study included surviving, active drivers in the cohort (N=125). MEASURES: The test battery assessed visual, cognitive, and physical abilities potentially relevant to driving, and was administered in participants' homes by trained interviewers between October 1994 and July 1995. Outcome measures included the self-report of a crash, moving violation, or being stopped by police in any Project Safety interview since the inception of the cohort. Analyses compared performance on the elements of the test battery with participants' histories of adverse driving events. RESULTS: Of the 125 drivers, 50 (40%) had reported an adverse event in a mean period of 5.76 (+/-.25) years before the current interview. The elements of the test battery independently associated with a history of events, adjusting for driving frequency, included near visual acuity worse than 20/40 (adjusted odds ratio 11.90), limited neck rotation (OR 6.10), and poor performance on a test of visual attention, the number cancellation task (OR 3.00). The resulting regression equation yielded a sensitivity of 80%, a specificity of 55%, and an area under the curve of .75 by receiver operating characteristic analysis. CONCLUSION: These findings suggest it may be possible to identify individuals potentially at risk for self-reported adverse driving events using simple tests of functional ability. If validated, such an approach could be used to identify individuals who need a more detailed assessment of functional abilities to determine the severity and etiology of impairments, and their effect on driving performance, as well as possible interventions to correct or compensate for the impairments.

Strategic planning with multitype libraries in the community: a model with extra funding as the main goal.

Medical libraries are discovering that ongoing collaboration in fundraising with other types of community libraries is mutually beneficial. Such partnerships may lead to joint grants, increase library visibility and access to decision makers, allow participation in community information networks, and provide leverage in additional fundraising projects. These partnerships have the potential to raise the profile of libraries. The accompanying community recognition for the parent organization may create a positive image, draw patients to the health center, and position the library and institution for future success in fundraising. Within institutions, development officers may become allies, mentors, and beneficiaries of the medical librarian's efforts. For a planned approach to community outreach with extra funding as the major objective, busy medical library administrators need guidelines. Standard participative techniques were applied to strategic planning by Indianapolis libraries to help achieve successful community outreach and to write joint statements of mission, vision, goals, and objectives.

The effects of platelet-derived growth factor-BB and insulin-like growth factor-1 on epithelial dysplasia.

Growth factors are multi-functional and multi-targeted proteins which play a significant role in wound healing. Platelet-derived growth factor B-chain homodimer (PDGF-BB) and insulin-like growth factor-1 (IGF-1) have demonstrated efficacy for periodontal regeneration in animal models. Although primarily associated with wound healing, PDGF-BB and IGF-1 also facilitate growth of a number of malignant neoplasms. Of particular concern to periodontists is epithelial dysplasia, a necessary precursor to squamous cell carcinoma, the most common oral malignancy. Certain risk factors for oral cancer, such as tobacco, age, and alcohol, are also associated with an increased incidence of periodontal disease. The effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia have not previously been reported. The purpose of this study was to examine the effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia induced in the buccal cheek pouch of the Syrian golden hamster. A total of 66 hamsters received 18 applications of 0.5% dimethylbenzanthracene (DMBA), a topical carcinogen, over a 6-week period for the induction of dysplasia. The hamsters were subsequently divided into a baseline and 3 experimental groups (growth factors, saline vehicle, untreated control). Following the final DMBA application (day 0), the baseline group (N = 6) was sacrificed, the growth factor group (N = 21) received a single injection in the cheek pouch containing 4 micrograms of PDGF-BB and 4 micrograms of IGF-1 in saline, the saline group (N = 19) received an injection in the cheek pouch containing the saline vehicle only, and the untreated control group (N = 20) received no injection. Animals in experimental groups were sacrificed on days 3, 6, and 10. The cheek pouches were harvested for histologic and histochemical evaluation. Dysplasia was histologically graded from 0 to 4. Statistical analysis of the histologic data revealed no significant differences either by sacrifice date or by group. Histochemical evaluation, via staining for gamma-glutamyl transpeptidase (GGT), a marker for dysplastic cell colonies, revealed that the density of GGT-positive cells in experimental groups differed significantly from baseline levels. No significant differences were detected between experimental groups. There was poor correlation between the density of GGT-positive cells and the histologic grading of dysplasia. It is concluded that exposure to PDGF-BB and IGF-1 had no demonstrable effect on epithelial dysplasia in this hamster model.

Computer-assisted coregistration of multislice SPECT and MR brain images by fixed external fiducials.

We have developed and validated in a phantom a method of computer-assisted coregistration using multislice SPECT and MR images. Reusable fiducial markers were fabricated from nylon-based plastic and consist of two parts: a base that remains fixed to the skin with adhesive between scans and a removable, spherical cavity insert that can be filled with contrast agents appropriate for multiple imaging modalities. Markers external and internal to a three-dimensional brain phantom provided a means of quantifying the method's accuracy. A computer algorithm was used to derive transformation matrices for image sets by minimizing the root mean squared deviations obtained for multiple permutations (n = 10) of increasing numbers (range 3-11) of external SPECT/MRI point pairs. As defined by the average +/- SEM mean residual deviations of noncoregistered internal fiducials, the minimal accuracy was 2.4 +/- 0.3 mm (no marker > 3.6 mm) for three coregistration points and did not improve beyond seven to eight fiducials (2.2 +/- 0.1 mm; no marker > 3.2 mm). The method's true accuracy is likely to be better than estimates of minimal accuracy, however, since such measures reflect surmountable random errors in fiducial location. With use of identical MRI (or SPECT) data sets, measures of intraoperator (0.5 +/- 0.1 and 0.5 +/- 0.1 mm, respectively) and interoperator (0.5 +/- 0.3 and 0.8 +/- 0.1 mm) reliability were also obtained, establishing the method as highly reproducible and objective. Preliminary results in a human subject suggest its feasibility for clinical studies.

Inhibition of hamster buccal pouch carcinogenesis by limonin 17-beta-D-glucopyranoside.

Limonin 17-beta-D-glucopyranoside, nomilin 17-beta-D-glucopyranoside, and nomilinic acid 17-beta-D-glucopyranoside, three limonoid glucosides isolated from oranges, were tested for cancer chemopreventive activity. Eighty female Syrian hamsters were divided into four equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside (Group III), or nomilinic acid 17-beta-D-glucopyranoside (Group IV). After this initial treatment, the left buccal pouches of 16 hamsters from each group were painted five times per week. Two or three times per week the pouches were treated with a 0.5% solution of the carcinogen 7,12-di-methylbenz[a]anthracene (DMBA) dissolved in mineral oil. On alternate days, the pouches were treated with water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside, or nomilinic acid 17-beta-D-glucopyranoside. The 16 remaining animals were used as controls. These hamsters were treated five times per week, one day with mineral oil and the next with either water (Group I) or one of the 3.5% solutions of the limonoid glucosides (Groups II-IV). After 15 weeks (71 applications), the hamsters were killed. Multiple tumors were common in the animals treated with DMBA; however, the animals treated with limonin 17-beta-D-glucopyranoside exhibited a 55% decrease in average tumor burden. Further comparisons between Groups I and II showed that this reduction in tumor burden was mainly due to a decrease in tumor mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Kahweol and cafestol: inhibitors of hamster buccal pouch carcinogenesis.

Kahweol and cafestol, two compounds extracted from green coffee beans, were tested for cancer chemopreventive activity. For the experiment, 60 hamsters were divided into three equal groups and placed on one of three diets. The animals in Group I received a normal diet, whereas the animals in Groups II and III received the same diet supplemented with a 50:50 mixture of kahweol and cafestol. The content of the kahweol and cafestol mixture in these two diets was 0.2 g/kg of food (Group II) and 2.0 g/kg of food (Group III). After the hamsters adjusted to their respective diets, 16 hamsters from each group were selected. The left buccal pouches of these animals were painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil. The 12 remaining hamsters were used as controls. The left buccal pouches of these animals were painted three times weekly with mineral oil. After 13 weeks (39 applications) the hamsters were killed. Multiple tumors were common in animals treated with DMBA; however, the animals receiving kahweol and cafestol in the diet (2 g/kg of food) exhibited a 35% reduction in tumor burden. Further comparisons between Groups I and III showed that this reduction in tumor burden was due to a decrease in tumor number. The results for Group II were inconclusive. Some reduction in tumor number was found, but this was offset by an increase in the size of the tumors.

The effect of citrus limonoids on hamster buccal pouch carcinogenesis.

Two citrus limonoids, limonin and nomilin, were tested for their effects on the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced buccal pouch epidermoid carcinomas. Forty-five female Syrian hamsters were divided into three equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of dimethylsulfoxide (DMSO) (group I), a 2.5% solution of limonin dissolved in DMSO (group II) or a 2.5% solution of nomilin dissolved in DMSO (group III). After this initial treatment, 11 hamsters from each group were selected. The left buccal pouches of these animals were painted 2 or 3 times weekly with a 0.5% solution of DMBA in mineral oil. On alternate days the pouches were painted with DMSO (I), the 2.5% solution of limonin (II) or the 2.5% solution of nomilin (III). The 12 remaining hamsters were used as controls and were painted with mineral oil and DMSO (I), mineral oil and the 2.5% solution of limonin (II), or mineral oil and the 2.5% solution of nomilin (III). After 15 weeks the hamsters were killed, the pouches were excised and the tumors were counted and measured. Tumors of variable size were common in the animals treated with DMBA. However, the animals receiving topical applications of limonin exhibited a 60% reduction in tumor burden. Further comparisons between groups I and II showed that this reduction in tumor burden was due to a 20% decrease in tumor number and a 50% decrease in tumor mass. The results for group III showed that nomilin was considerably less effective as an inhibitor of DMBA-induced neoplasia.

Analgesic effects of 3-methoxybenzamide in rats.

The i.p. injection of 3-methoxybenzamide (3-MBA) in rats produces a dose-related elevation of the threshold for response to a painful stimulus. Metoclopramide, also a substituted benzamide, has analgesic activity that is attenuated by bromocriptine, a dopamine receptor agonist, and by the narcotic antagonist, naloxone, suggesting involvement of dopamine and opiate receptors in the action of this drug. The involvement of these receptors in the analgesic action of 3-MBA has been examined using L-dopa and naloxone. Neither significantly altered the analgesic action. Although the results are preliminary, the analgesic action of 3-MBA would not seem to occur via opiate or dopamine receptors.

Inhibition of hamster buccal pouch carcinogenesis by green coffee beans.

Forty female Syrian Golden hamsters were divided into two equal groups and placed on one of two diets. The hamsters in Group I received a normal chow, and the animals in Group II were given the same chow supplemented with powdered green coffee beans (20%). After the hamsters adjusted to the diets, 16 animals from each group were selected. The right buccal pouch of each of these hamsters was painted three times weekly with a 0.5% solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in heavy mineral oil. The eight remaining animals, four in each group, served as controls and were treated three times weekly with heavy mineral oil. After a total of 50 treatments (16 1/2 weeks), the hamsters were killed. The animals receiving green coffee beans exhibited a significant delay in the development of DMBA-induced carcinogenesis of the buccal pouch mucosa, as determined by both visual and histologic examination.

Increased ionic strength: effects on DNA fragmentation and poly(ADP-ribose) polymerase activity in HeLa nuclei.

Poly(ADP-ribose) polymerase activity was measured in a crude nuclear fraction isolated from HeLa cells. It was found that the addition of ammonium sulfate or other salts to the standard incubation medium inhibited the formation of poly(ADP-ribose). Through the use of alkaline sucrose density gradients it was also noted that this same increase in ionic strength inhibited the in vitro breakdown of the HeLa DNA. Additional experiments with alkaline sucrose density gradients and deoxyribonuclease I showed that the in vitro activity of poly(ADP-ribose) polymerase is largely dependent upon DNA fragmentation but that DNA fragmentation at least in vitro is not dependent upon the formation of poly(ADP-ribose). These observations imply that this nuclear enzyme is not extremely sensitive to changes in the ionic strength of the reaction media but is affected indirectly, supposedly through changes in the endonuclease activity of the HeLa nuclei. If this proves to be true, then the addition of salt to the incubation medium for poly(ADP-ribose) polymerase could prove to be a valuable tool for the study of ADP-ribosylation reactions.

In vivo studies on the carcinogenic potential of an orthodontic bonding resin.

Data from another laboratory have indicated that the individual components of an orthodontic bonding resin might contain a carcinogen. Since that report, the formulation of the product was changed. The purpose of this study was to determine whether the new product is safe. Three groups of rats were used for the experiment. One group served as a control, while the other groups ingested the sealant resin or sealant catalyst. The materials were suspended in an alcohol-aqueous mixture and the solutions were given to the animals as their only source of fluid. The exposure was for 1 year. After this period of time, all the rats were given tap water and observed until day 600. The animals were autopsied at time of death or at the end of the experiment. During the treatment, there were significant differences (p less than 0.01) in water intake among the three groups. The average intake per day for the animals in the control group, the resin group, and the catalyst group was 50.2 cc, 37.8 cc, and 42.2 cc, respectively. Several animals died during the experiment, but there was no significant differences in the life expectancy of the animals in the three groups. The autopsies uncovered one malignant neoplasm, an undifferentiated sarcoma, in a rat from the control group and four benign tumors in rats from the three groups. All of these results indicate that the new formulation of the orthodontic bonding resin is not carcinogenic when ingested at a dose level of 50 ppm.

N-nitrosodimethylamine carcinogenesis in nicotinamide-deficient rats.

Special diets that were extremely low in protein (5.5%) and high in carbohydrate were used to test the effect of nicotinamide on N-nitrosodimethylamine-induced carcinogenesis in Holtzman albino rats. The level of nicotinamide in the three diets ranged from 0 mg/kg of food to 50 mg/kg to 500 mg/kg. During the treatment with these diets (5 weeks) and the carcinogen (18 days), the renal and hepatic concentrations of nicotinamide adenine dinucleotide-reduced nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate-reduced nicotinamide adenine dinucleotide phosphate were measured. In the liver, the concentration of these coenzymes fell well below normal levels, and significant differences between the two extreme diets (0 and 500 mg/kg) were found in the hepatic content of nicotinamide adenine dinucleotide-reduced nicotinamide adenine dinucleotide. In the kidney, the treatment with special diets and carcinogen had less effect. The content of nicotinamide adenine dinucleotide phosphate-reduced nicotinamide adenine dinucleotide phosphate remained normal, and the only significant drop in the concentrations of nicotinamide adenine dinucleotide-reduced nicotinamide adenine dinucleotide phosphate occurred in the animals on the nicotinamide-deficient diet. After the treatment, all of the animals were returned to the same standard diet. During the remainder of the experiment, 85 weeks, it was found that the initial treatments had not affected tumor incidence levels or tumor type, but had altered the rate of tumor incidence. These differences could be seen by comparing the results for the rats that had been given the nicotinamide-deficient diet to the results for the animals receiving an excess of the vitamin.