Milk and kefir maintain aspects of health during doxorubicin treatment in rats.

Doxorubicin (DOX), a powerful anthracycline antibiotic commonly used to treat a wide variety of cancers, is associated with the production of reactive oxygen species that cause oxidative damage, resulting in cardiac dysfunction. Components of dairy may have protective effects against DOX-induced cardiac damage. Kefir is a naturally fermented milk product containing antioxidants, probiotic bacteria, and yeast in addition to the protective components of dairy. We explored the effects of dietary milk and kefir on DOX-induced cardiotoxicity in rats. We used singly housed, 10-wk-old male Sprague Dawley rats assigned to 1 of 3 isocaloric diets, control (CON n = 24), milk (MLK, n = 24), or kefir (KEF, n = 24), with equivalent macronutrient profiles. After a 9-wk dietary intervention, all animals were given either a bolus injection (15 mg/kg) of DOX (CON-DOX n = 12; MLK-DOX n = 12, KEF-DOX n = 12) or saline (CON-SAL n = 12; MLK-SAL n = 12; KEF-SAL n = 12). Body weight, grip strength, echocardiographic evaluation of cardiac geometry, and cardiac function were evaluated using echocardiography at 5 d postinjection and data were analyzed using ANOVA. Survival at d 5 post-DOX injection was 92 and 100% in KEF-DOX and MLK-DOX, respectively, and 75% in CON-DOX. By the last week of the dietary intervention, and just before injection with saline or DOX, CON weighed significantly (14%) more than the MLK and KEF. The DOX treatment resulted in significant reductions in body weight; however, we found no diet × drug interactions. The DOX treatment reduced peak grip strength compared with SAL; when compared with pre-injection measures, MLK-DOX rats did not experience a significant reduction in peak grip strength compared with CON-DOX and SAL-DOX rats. Heart mass in MLK and KEF was significantly higher when compared with CON. In summary, 9 wk of milk or kefir ingestion resulted in lower body size and higher heart mass after DOX treatment. Additionally, MLK preserved peak grip strength after DOX treatment, whereas KEF or CON did not. We observed no consistent protective effects with respect to heart dimensions and function. These findings suggest that long-term milk or kefir ingestion may be helpful in optimizing health before and during doxorubicin treatment.

Short communication: Sensory analysis of a kefir product designed for active cancer survivors.

Kefir is a fermented milk product that is a good source of protein and health-promoting bacteria. It has the potential to improve recovery from exercise and the health and well-being of cancer survivors. The purpose of this study was to explore cancer survivor attitudes about and acceptance of a kefir recovery beverage made from cultured milk, whole fruit, natural sweeteners, and other natural ingredients. Kefir was made by inoculating and fermenting milk with kefir grains. The kefir was then mixed with a fruit base and given to cancer survivors (n = 52) following a bout of exercise. Participants evaluated the acceptability of the beverage samples (overall appearance, aroma, taste, mouthfeel, and overall liking) using a 9-point hedonic scale, and they evaluated the smoothness using a 3-category just-about-right scale (not enough, just about right, and too much). They also expressed their physical and psychological feelings about the beverage using a 5-point scale (1 = not at all to 5 = extremely) and indicated their purchase intent using a binomial (yes/no) response. The health benefits of kefir were then explained, and participants sampled a second beverage (the same product), answering the same questions related to overall liking, feeling, and intent to purchase. We used a paired Student's t-test to compare beverage liking and emotion scores before and after participants learned about the health benefits of kefir. Data are presented as mean ± standard deviations. The beverage scored significantly higher for overall liking after the health benefits were explained (6.5 ± 1.8 and 7.0 ± 1.7 out of 9 before and after the explanation of health benefits, respectively). Participants showed a high intent to purchase before they learned about the health benefits (75% of participants indicated an intent to purchase, and 89% after they learned about the health benefits). The beverage received high scores overall and, except for an improvement in overall liking, we observed no significant differences in physical and psychological feelings before and after participants learned that it contained kefir and had potential health benefits. We found the beverage to be acceptable for consumption by cancer survivors, and the majority of participants showed an interest in purchasing for after exercise.

The effects of postexercise consumption of a kefir beverage on performance and recovery during intensive endurance training.

This study was designed to determine whether kefir accentuates the positive health benefits assessed by measures in fitness, body composition, or both, as a measure of cardiovascular disease risk as well as the biomarker C-reactive protein (CRP). Sixty-seven adult males and females aged 18 to 24 yr were assigned to 1 of 4 groups: (1) endurance training + control beverage, (2) endurance training +kefir beverage,(3) active control + control beverage, or (4) active control + kefir beverage. The exercise groups completed 15 wk of structured endurancetraining while the active control groups maintained their usual exercise routine. Additionally, each group was assigned to either a kefir or a calorie/macronutrient matched placebo beverage that was consumed twice per week. No significant interactions were found among groups with respect to outcome variables with the exception of serum CRP. The endurance training was effective in improving 1.5-mile (2.41 km) times and kefir supplementation may have been a factor in attenuating the increase in CRP that was observed over the course of the intervention period. This preliminary study suggests that kefir may be involved in improving the risk profile for cardiovascular disease as defined by CRP.

In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity.

Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD + quercetin (HF + Q), or HFD + RO (HF + RO) for 9 weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF + Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF + Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin-but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.

Failure of dietary quercetin to alter the temporal progression of insulin resistance among tissues of C57BL/6J mice during the development of diet-induced obesity.

AIMS/HYPOTHESES: High-fat diets produce obesity and glucose intolerance by promoting the development of insulin resistance in peripheral tissues and liver. The present studies sought to identify the initial site(s) where insulin resistance develops using a moderately high-fat diet and to assess whether the bioflavonoid, quercetin, ameliorates progression of this sequence. METHODS: Four cohorts of male C57BL/6J mice were placed on diets formulated to be low-fat (10% of energy from fat), high-fat (45% of energy from fat) or high-fat plus 1.2% quercetin (wt/wt). After 3 and 8 weeks, cohorts were evaluated using euglycaemic-hyperinsulinaemic clamps, metabolomic analysis of fatty acylcarnitines and acute in vitro assessments of insulin signalling among tissues. RESULTS: After 3 and 8 weeks, the high-fat diet produced whole-body insulin resistance without altering insulin-dependent glucose uptake in peripheral tissues. The primary defect was impaired suppression of hepatic glucose production by insulin at both times. Quercetin initially exacerbated the effect of high-fat diet by further increasing hepatic insulin resistance, but by 8 weeks insulin resistance and hepatic responsiveness to insulin were similarly compromised in both high-fat groups. The high-fat diet, irrespective of quercetin, increased short-chain fatty acylcarnitines in liver but not in muscle, while reciprocally reducing hepatic long-chain fatty acylcarnitines and increasing them in muscle. CONCLUSIONS/INTERPRETATION: Failure of insulin to suppress hepatic glucose output is the initial defect that accounts for the insulin resistance that develops after short-term consumption of a high-fat (45% of energy) diet. Hepatic insulin resistance is associated with accumulation of short- and medium-, but not long-chain fatty acylcarnitines. Dietary quercetin does not ameliorate the progression of this sequence.

Resistive exercise blunts LPS-stimulated TNF-alpha and Il-1 beta.

To examine the influence of acute resistive exercise and "hormone status" on cytokine profile, 35 postmenopausal women (72 +/- 6.2 yr) underwent a moderate-high-intensity resistive exercise bout or rested. There were 4 groups: no hormone replacement (NHR, n = 9), hormone replacement (HRT, n = 12), selective estrogen receptor modulator (SER, n = 7), or resting control (no hormone replacement, CON, n = 7). NHR, HRT, and SER exercised (3 sets, 10 exercises @ 80 % 1RM). Blood was collected pre-exercise (PR), postexercise (PO), and two hours (2H) postexercise (same times for CON). Blood was diluted 1 : 10 in culture medium and incubated (37 degrees C, 5 % CO2, 24 h) with lipopolysaccharide (LPS, 25 microg . ml (-1)). Serum and supernatant from LPS-stimulated blood were analyzed for IL-6, IL-1 beta, and TNF-alpha using ELISA. Resistive exercise increased PO serum IL-6, and PO LPS-stimulated IL-6 and IL-1 beta in the exercise groups (HRT, NHR, SER collapsed; EX, n = 28). LPS-stimulated IL-1 beta remained elevated at 2H in EX and was significantly higher than PR in CON at 2H. Expressed per monocyte, EX had significantly lower IL-1 beta and TNF-alpha LPS-stimulated production at PO and 2H compared to CON, indicating an exercise-induced blunting of an apparent diurnal response on cytokine production. In postmenopausal women, acute resistive exercise increased circulating IL-6, but reversed an apparent diurnal increase in LPS-stimulated IL-1 beta and TNF-alpha production with no influence of hormone replacement or raloxifene.

Measurement of body composition changes with weight loss in postmenopausal women: comparison of methods.

BACKGROUND: The accurate measurement of body composition changes is important when evaluating the efficacy of medical nutrition therapy and weight management programs, yet is not well documented in older women. OBJECTIVE: We compared methods of estimating energy-restriction-induced body composition changes in postmenopausal women. DESIGN: 27 women (59 +/- 8 y; BMI 29.0 +/- 2.9 kg/m2; mean +/- SD) completed a 9-wk energy restriction period (5233 kJ/d, (1250 kcal/d)). Changes in % body fat (delta%BF), fat mass (deltaFM), and fatfree mass (deltaFFM) were measured by hydrostatic weighing (HW), air-displacement plethysmography (ADP), dual-energy x-ray absorptiometry (DXA), and deuterium oxide dilution (D2O). The Baumgartner et al. (Am J Clin Nutr 53:1345-1353, 1991) four-compartment (4C) model with body volume from HW was the criterion method. The 4C model with body volume from ADP was also compared. Regression equations were developed based on 4CHW (dependent variable) utilizing results of change (POST-PRE) for each method. RESULTS: The women lost 6.8 +/- 3.2 kg; 9% of baseline weight. Based on 4CHW, the body composition changes were -2.4 +/- 4.5 delta%BF, -4.7 +/- 3.3 kg deltaFM, and -2.6 +/- 4.4 kg deltaFFM. No differences were detected by ANOVA for delta%BF, deltaFM, and deltaFFM among 4CHW, HW, ADP, DXA, D2O, and 4CADP. Bland-Altman limits of agreement showed differences between methods that ranged from 14.5 to -14.1 delta%BF, 7.8 to -8.1 kg deltaFM, and 7.5 to -8.4 kg deltaFFM for individuals. A bias was shown with 4CADP overestimating delta%BF (1.4 %) and FM (0.6 kg) and underestimating deltaFFM (-1.2 kg) compared to 4CHW. The regression model was acceptable for %BF (4CADP, 2CHW, and 2CD2O); FM and FFM (4CADP, 3CDXA, 2CHW, and 2CD2O), but not for other estimates of %BF, FM, FFM. CONCLUSIONS: These body composition assessment methods may be used interchangeably to quantify changes in % body fat, fat mass, and fat-free mass with weight loss in groups of postmenopausal women. 4CADP overestimates delta%BF and underestimates deltaFFM. When utilizing one of these comparison methods (4CADP, 3CDXA, 2CHW, 2CD2O) to quantify changes in fat mass and fat-free mass for an individual postmenopausal woman, regression equations may be used to relate the data to 4CHW.

Transperineal and transvaginal sonography of perianal inflammatory disease.

OBJECTIVE: Perianal infection arises in small intersphincteric anal glands predominantly located at the dentate line. Documentation of fluid collections and the relationship of inflammatory tracts to the sphincter mechanism is important for surgical treatment. Transanal sonography for assessment of perianal inflammatory disease is limited because placement of the rigid probe into the anal canal does not allow assessment of disease in the perineal region. The purpose of this study was to validate the use of transperineal sonography in men and both transvaginal and transperineal sonography in women for evaluation of perianal inflammatory disease. SUBJECTS AND METHODS: Fifty-four patients, 28 men and 26 women, were imaged with transperineal and a combination of transperineal and transvaginal sonography, respectively. All patients were examined in the supine lithotomy and left lateral position with a transvaginal 8-to 4-MHz probe or a linear 12- to 7-MHz transducer. All fluid collections, sinus tracts, and fistulas were described by their location in relation to the sphincter mechanism and perineum. RESULTS: Forty-six of 54 patients had perianal fistulas or sinus tracts: 33 transphincteric, seven intersphincteric, and six extrasphincteric. Fifteen patients had an associated abscess. In the eight remaining patients, there were two anovaginal fistulas, one rectovaginal fistula, one prolapsed internal hemorrhoid, two perianal complex masses, and two vascular perianal or perirectal inflammatory masses. Twenty-six patients underwent surgical procedures involving the anorectal canal or perirectal region, and of these, preoperative sonographic findings were confirmed in 22 (85%) of 26 patients. Three patients refused surgery, and six are awaiting surgery at this writing. Fifteen patients were treated conservatively. CONCLUSION: Transperineal and transvaginal sonography are accurate, painless, and cost-effective methods for documenting perianal fluid collections and fistulas or sinus tracts or both.

Transvaginal sonography of the anal sphincter: reliable, or not?

OBJECTIVE: The purpose of this study was to validate the use of transvaginal sonography for anal sphincter evaluation, compare this technique with the more commonly used transanal technique, and explain a publication that suggested that transvaginal sonography is unreliable. SUBJECTS AND METHODS: The study population consisted of 50 women, of whom 44 prospectively underwent transanal and transvaginal sonography. The six remaining patients with surgical confirmation underwent only transvaginal sonography. All images were interpreted by the examining radiologist and then reviewed by a second radiologist who was unaware of the first radiologist's interpretations. Defects in the external and internal anal sphincters, the status of the perineal body, and any perianal collections or fistulas were documented. RESULTS: Twenty-five of the 50 patients showed sphincteric defects. Twenty-two had a defect in the external anal sphincter, of whom 16 had a matching internal anal sphincter defect. Four patients had an isolated internal anal sphincter defect. Surgery in nine of these 22 patients confirmed the defects seen on sonography. The 10th patient who underwent surgery had scar tissue rather than a tear in the external anal sphincter that corresponded with the defect seen on sonography. Defects were identified in all patients presenting with fecal incontinence who had undergone either a primary repair or an anterior sphincteroplasty. Of the 25 patients with intact sphincters on both transvaginal and transanal sonography, four had other significant findings including two perianal abscesses and two T3 rectal carcinomas. In 40 of the 44 patients who were prospectively imaged using both techniques, the sonographic findings were in agreement. Review, performed by a second radiologist who was unaware of the first radiologist's interpretations, verified the findings resulting in an 88.6% interobserver agreement. In all patients, perineal body assessment and assessment of perianal inflammatory disease was more accurate with the transvaginal technique. CONCLUSION: Transvaginal sonography is a reliable method for evaluating the anal sphincter, with an accuracy equivalent to that of the transanal technique. Transvaginal sonography is preferable for evaluation of the perineal body and perianal inflammatory processes.

Active and passive surveillance for communicable diseases in child care facilities, Seattle-King County, Washington.

OBJECTIVES: The purpose of this study was to develop and evaluate models for public health surveillance of illnesses among children in out-of-home child care facilities. METHODS: Between July 1992 and March 1994, 200 Seattle-King County child care facilities participated in active or enhanced passive surveillance, or both. Reporting was based on easily recognized signs, symptoms, and sentinel events. Published criteria were used in evaluating surveillance effectiveness, and notifiable disease reporting of participating and nonparticipating facilities was compared. RESULTS: Neither surveillance model was well accepted by child care providers. Enhanced passive and active surveillance had comparable sensitivity. Reporting delays and the large amount of time needed for data entry led to problems with timeliness, especially in terms of written reporting during active surveillance. CONCLUSIONS: Widespread active public health surveillance in child care facilities is not feasible for most local health departments. Improvements in public health surveillance in child care settings will depend on acceptability to providers.

Risk of infection with hepatitis A, B or C, cytomegalovirus, varicella or measles among child care providers.

BACKGROUND: Employment as a child care provider has been suggested as an indication for hepatitis A virus (HAV) immunization; however, whether this occupational group is at increased risk of HAV infection is not well-defined. METHODS: We obtained sera samples for testing for antibodies to hepatitis A, B and C, cytomegalovirus, varicella and measles from a sample of child care providers in King County, WA, and administered a questionnaire to assess employment characteristics and other potential risk factors for infection. We also compared the anti-HAV seroprevalence among providers with that of subjects in the Third National Health and Nutrition Survey, representative of the US general population. RESULTS: Thirteen percent (48 of 360) of providers were anti-HAV-positive (46% (22 of 47) of foreign born vs. 8% (26 of 313) of US-born (P < 0.001)). In multivariate analysis anti-HAV seropositivity was associated with foreign birth, age, income and Hispanic ethnicity but was not associated with characteristics of employment. Seroprevalence among US-born providers tended to be lower than that among Third National Health and Nutrition Survey subjects of similar age, sex, race and income. Sixty-two percent of providers were seropositive to cytomegalovirus, which was associated with nonwhite race, changing diapers > or = 3 days/week while at work and having a child in the household. Antibody prevalence was 1.4% to hepatitis B core antigen, 0.6% to hepatitis C, 94% to measles and 98% to varicella. CONCLUSIONS: The anti-HAV prevalence among US-born providers was low, and seropositivity was not associated with employment characteristics, indicating that occupational exposure to HAV is uncommon under non-outbreak circumstances.

Nutrition of the Asian adolescent girl.

A comparison of sex differential mortality rates indicates that women are at increased risk in several countries of Asia, in part due to less access to a variety of services and lower priority for food than their male siblings. Poorer nutritional status becomes apparent during adolescence, with a delay in maturation which may have repercussions for subsequent ability of the biologically immature woman to carry through a normal pregnancy. There is a dearth of information on girls during this vulnerable period of life which is recently being corrected by studies in Nepal, India and the Philippines where the magnitude of dietary risk is being compared with its impact on nutritional status and the sociocultural factors that may be responsible.

PIP: The excess female mortality rate seen in Asia is explained by 2 hypotheses. One posits that sex differences in causes of death are relatively constant from country to country, but the proportion of deaths assigned to any one cause varies. The other states that sex differences vary with circumstances; thus, inadequate nutrition for females would result in a higher death rate. In Asia, discrimination against girls begins before birth and can be revealed by an examination of family and community status indicators. Sexual differences in resistance to disease obscure data to support the inequity hypothesis, but the degree to which mortality rates differ from the biological bias may be a crude measure of inequity. Disparities in nutrition are also masked by data which are combined for boys and girls under age 14 years and then combined for all females over age 14 years. Regional surveys in India, Bangladesh, and Indonesia show that the dietary intake of adolescent girls is likely to be inadequate. Delayed menarche may be an index of poorer nutrition, but it may also be attributable to a high intake of dietary fiber. Another sign of malnutrition is the percentage of growth which takes place after menarche. In well-nourished girls, only 5-10% of growth remains; poorly-nourished girls may grow an additional 20%. Since these are the same girls who marry young, this late attainment of full stature may contribute to high maternal mortality rates. Factors which contribute to the malnutrition of adolescent girls include a lack of understanding of their needs which is exacerbated by taboos which prevent women from consuming some foods during menses. Many questions remain to be answered about the causes of poor nutrition in Asian adolescent girls. Studies currently underway in Bombay, the Philippines, and Nepal may provide some answers needed to design programs to meet the needs of this group.

Oligonucleotide capture during end joining in mammalian cells.

Extra nucleotides (termed filler DNA) are found at about 10% of the junctions of the genetic rearrangements that arise by illegitimate recombination in mammalian cells. Such filler DNAs could arise by the joining of oligonucleotide fragments to broken ends prior to end joining. We tested this possibility by microinjecting mixtures of defined oligonucleotides with SV40 genomes that were linearized in the intron for T antigen, a site where incorporation of extra nucleotides does not impair viability. Using an injection ratio of 1000 oligonucleotides per DNA end, we screened viable genomes for incorporation of single-stranded and double-stranded oligonucleotides with varying degrees of complementarity to the ends of the linear SV40 molecules. Genomes from 510 independent plaques were screened by restriction digestion to identify those that had picked up a restriction site unique to the injected oligonucleotides. Double-stranded oligonucleotides that were fully complementary to the SV40 ends were readily incorporated, but uptake of the other oligonucleotides was not detected by restriction analysis. Nucleotide sequences of junctions from 12 genomes derived from co-injection of noncomplementary oligonucleotides revealed two with filler DNA, but neither could be assigned unambiguously to the injected oligonucleotides.

Parents' constructions of their infants' personalities before and after birth: a descriptive study.

Thirty five middle class parents, pregnant for the first time, were recruited from childbirth classes for participation in a shortterm longitudinal study of parents' constructions of their infants' personalities during pregnancy and in early infancy. Here, we report qualitative findings about parents' descriptions of their infants' personalities before and after birth, as well as descriptions of their relationships with their infants and their first feelings of love for their infants. Descriptions of infant personalities were remarkably vivid before and after birth, but there were changes in the prominence of several attributes over time.