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Biomedical subjects

Ram Reifen

Publications and source records attributed to Ram Reifen.

At least 19 recordsLinked to original sources

Mucosal function in rat jejunum and ileum is altered by induction of colitis.

Many studies dealing with trinitrobenzene sulfonic acid (TNBS) colitis in rats have been carried out referring only to the colon. In humans, ulcerative colitis (UC) can extend a variable distance into the terminal ileum in a phenomenon known as backwash ileitis (BWI). The aim of this study was therefore to examine the effect of TNBS-induced colitis on different aspects of the rat ileum and jejunum. We hypothesized that TNBS administration would lead to a systemic influence on the small intestine. Rats were induced colitis by administration of 0.25 ml of 2,4,6-trinitrobenzene sulfonic acid and 72 h after colitis induction animals were sacrificed. Segments were taken of the colon, ileum and jejunum. In addition to mucin mRNA expression, morphological changes were observed in the jejunum and ileum. We examined the mRNA expression and biochemical activity of brush border enzyme, sucrase iso-maltase and aminopeptidase, in all three segments. The villous surface area of colitis-induced rats was smaller in jejunum and ileum compared to control. In the jejunum of TNBS-induced rats, goblet-cell volume increased and their density decreased. The relative amount of MUC2 mRNA decreased in the jejunum, ileum and colon of colitis rat. However, MUC3 mRNA expression increased in the ileum and colon of these rats. Sucrase isomaltase expression and activity decreased in the ileum of TNBS-induced rats, while aminopeptidase activity was lower in the jejunum. These observations suggest that intrarectal administration of TNBS to rats influences not only their colon and terminal ileum, but also the proximal ileum and jejunum. Involvement of the ileum and jejunum in TNBS-induced colitis may be related to the systemic reaction of the immune system and mucosa to colitis.

Aminopeptidases↗

Effect of nutrition on growth in short stature before and during growth-hormone therapy.

OBJECTIVE: Although nutritional counseling is an integral part of the management of rapidly growing children, few studies have focused on the importance of nutritional supervision during growth-hormone (GH) therapy. The objective of this study was to study the effect of caloric intake on growth before and during GH therapy. METHODS: A total of 115 short normal prepubertal children who were 7.4 +/- 1.2 years of age (mean +/- SD) and had height SD score (SDS) of -2.5 +/- 0.6 were treated with a GH dose range of 0.13 to 0.52 mg/kg per week for 1 year. A 3-day nutritional recall and blood chemistry analysis were repeated every 3 months. RESULTS: Caloric intake (expressed as % recommended dietary allowance) was positively correlated with the pretreatment growth velocity (SDS) and the increment in growth velocity SDS during the first year of GH therapy (r = 0.363 and 0.493). By stepwise regression analysis, we identified 4 parameters that could predict the 1-year increment in growth velocity SDS: the contribution of each factor (% variability) was pretreatment growth velocity SDS 36%, GH dose (27%), caloric intake 4%, and the integrated concentration of GH 2% (r(2) = 0.689). GH therapy induced an alkaline phosphatase increment of 59 +/- 49 IU/mL, an insulin-like growth factor-I increment of 32.6 +/- 11.9 nmol/L, and a GH binding protein increment of 10.2 +/- 2.7%. During GH therapy, an increase in serum transferrin (56.5 +/- 35.2 mg/dL) and a decrease in serum iron (20.5.5 +/- 20.2 microg/dL) were noted. These changes could not be detected through hemoglobin levels or hematopoietic indexes. Dietary iron supplementation reversed this phenomenon. CONCLUSIONS: The nutritional status of GH-treated patients before and throughout the course of GH treatment should be monitored closely to improve the growth response and prevent nutritional deficiencies. Special emphasis should be placed on iron nurture.

Alkaline Phosphatase↗

Longitudinal monitoring of bone measured by quantitative multisite ultrasound in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is characterized, among other features, by intestinal malabsorption of minerals, vitamins, and various food ingredients. This may cause a suboptimal peak bone mass and thereby susceptibility to osteoporosis at an early age. OBJECTIVE: Longitudinal measurement of bone in CD during active disease and during remission. DESIGN: We evaluated 24 patients with CD (16 males) 14 to 16 years of age longitudinally, every 3 months over 12 months, for disease activity. Longitudinal follow-up by quantitative ultrasound measurement using a bone sonometer (Sunlight Omnisense, Tel Aviv, Israel) that obtains axial speed of sound (SOS) was also performed. Eight of the CD patients were in remission (R-CD), characterized by accelerated weight and height gain and near-normal erythrocyte sedimentation rate and serum iron. Eight patients had active CD (A-CD), and 8 patients were under treatment with oxandrolone. RESULTS: By two-way repeated-measures analysis of variance, the change in SOS Z-score of tibia at 0, 6, and 12 months was as follows: -0.5 +/- 0.2 to -0.3 +/- 0.2, -0.6 +/- 0.2 to -1.0 +/- 0.5 and -0.6 +/- 0.2 to -0.4 +/- 0.2 in the remission, active disease, and oxandrolone-treated groups, respectively (P < 0.001). Similarly, the change in SOS Z-score of radius during the study was as follows: -0.5 +/- 0.3 to -0.6 +/- 0.3, -0.6 +/- 0.3 to -1.0 +/- 0.3 and -0.6 +/- 0.2 to -0.4 +/- 0.2 in the remission, active disease, and oxandrolone-treated groups, respectively (P < 0.001). While a small change over time in patients in remission was noted, SOS decreased in patients with active disease and increased in oxandrolone-treated patients. Despite the fact that SOS remained in the normative range in all patients, a clear deterioration was demonstrated for patients with active disease. CONCLUSIONS: We conclude that longitudinal follow-up of patients with active disease may detect an early pattern of deterioration in quality of bone.

Adolescent↗

Longitudinal monitoring of bone accretion measured by quantitative multi-site ultrasound (QUS) of bones in patients with delayed puberty (a pilot study).

OBJECTIVE: to compare the effect of anabolic agents on bone accretion in boys with constitutional delay of puberty (CGDP). RATIONALE: it has been suggested that an appropriate timing of puberty is necessary for normal bone mineral density (BMD) acquisition. Proper bone development during childhood is the key factor in achieving higher peak bone mass during middle age, which may not be achievable in CGDP children, and thereby osteoporosis may appear at an earlier age then expected. PATIENTS AND METHODS: 45 boys with CGDP aged 14-16 years were monitored longitudinally, every 3 months over 12 months with Sunlight Omnisense, a quantitative ultrasound device (Tel Aviv, Israel). The apparatus is a multi-site bone sonometer that obtains axial Speed of Sound (SOS). Based on a reference database obtained on n=1,085 (490 boys) 0-18 years, a normative curve was determined. Fifteen (14-16 years old) of the CGDP patients were treated with I.M. testovirone depot 100 mg monthly for 6 months, 15 (14-16 years old) were treated with oxandrolone 5 mg/m(2) daily for 6 months, and 15 (14-16 years old) were in an observation group. RESULTS: whereas the quantitative ultrasound (QUS) Z-score had shown some increase over time in CGDP-treated patients, an increase was found in tibia Z-score from -0.5(-0.64, -0.36) to -0.4(-0.54, -0.26) and from -0.52(-0.67, -0.38) to -0.31(-0.44, -0.11) in the testosterone and oxandrolone-treated groups, respectively, [median (25%, 75%)]. An increase in radius Z-score from -0.52(-0.65, -0.25) to -0.4(-0.54, -0.15) and from -0.51(-0.61, -0.21) to -0.37(-0.47, -0.07) in the testosterone- and oxandrolone-treated groups respectively [median (25%,75%)]. Z-score SOS decreased in the observation group -0.5(-0.66, -0.3) to -0.69(-0.85, -0.54) and -0.5(-0.59, -0.41) to -0.81(-0.95, -0.55) in tibia (P = 0.032) and radius (P = 0.029), respectively. Despite the fact that QUS remained in the normative range in all patients, a clear deterioration was demonstrated in untreated CGDP patients. CONCLUSION: longitudinal follow-up of patients with CGDP may detect an early pattern of deterioration of bone mass.

Adolescent↗

Vitamin A exerts its activity at the transcriptional level in the small intestine.

THE AIM OF THIS STUDY: was to examine the effects of vitamin-A deficiency on the small intestinal morphology and on brush-border enzyme function and expression. METHODS: Weanling male rats were fed a vitamin-A deficient (VAD), sufficient (VAS), or supplemented (VASUP) diet, or were pair-fed (PF) with the VAD rats. Average food intakes were not different among the groups. RESULTS: From days 35 to 42, the body weight of VAD rats began to plateau, whereas the other groups, including the PF rats, continued to gain weight. At days 48 to 51, the final mean body weight of VAD rats was significantly lower than that of PF, VAS and VASUP rats (P < 0.05). Serum and liver retinol levels were lower in VAD rats (by 85 % and 99%, respectively) and higher in the VASUP group (by 126 % and 160%, respectively) compared to the VAS group (P < 0.01). Histological examination of the jejunum revealed that in VAD rats the villi were shorter and thicker and there was an elevation in crypt depth relative to the other treatment groups. Infiltration of inflammatory cells was also observed in the jejunum of most of the VAD rats, but not in rats from other groups. Biochemical assays revealed that in VAD rats, alkaline phosphatase (ALP) and sucrase-isomaltase (SI) activities are significantly decreased in the jejunum, compared to PF, VAS and VASUP groups (P < 0.01). ALP activity was decreased in the duodenum of VAD rats as well. By comparison, amino-peptidase (AP) activity per mg protein in the jejunum and ileum of VAD rats was significantly increased compared to VAS and VASUP rats (P < 0.01), but was not different from PF rats. In all of the small intestinal sections, mRNA expression of all three brush-border enzymes relative to beta-actin were significantly lower in VAD rats than in the other treatment groups. SI was similarly expressed in all of the small intestinal organs, whereas AP and ALP expression varied. CONCLUSIONS: Our results suggest that vitamin-A deficiency modifies the maturation and differentiation processes of the small intestinal mucosa at the transcriptional and post-transcriptional levels respectively. This in turn may be one explanation for the alteration or elimination of nutrient digestion and absorption during VAD.

Alkaline Phosphatase↗

5-ASA and lycopene decrease the oxidative stress and inflammation induced by iron in rats with colitis.

BACKGROUND: Supplementation of 5-aminosalicylic acid (5-ASA) and of iron are among the principal therapies in patients with inflammatory bowel disease. Therapeutic iron, as well as heme iron from chronic mucosal bleeding, can increase iron-mediated oxidative stress in colitis. This study was designed to examine the influence of iron supplementation on histological expression and oxidative status relative to 5-ASA treatment and antioxidant treatment. METHODS: Colitis was induced using the iodoacetamide rat model, and rats were divided into different dietary groups of 6 rats each: 1, normal chow diet (control); 2, diet supplemented with iron; 3, iron supplementation and lycopene; 4, iron and Beta-carotene; 5, 5-ASA; 6, 5-ASA and lycopene; 7, 5-ASA and iron; 8, 5-ASA, iron, and lycopene. The animals were killed after 3 days and the weight of the ulcerated area recorded. Mucosal specimens were histologically evaluated. Myeloperoxidase (MPO) was measured to evaluate inflammatory status (U/g). Malondialdehyde (MDA) was measured in colonic tissue ( micro mol/g) and superoxide dismutase (SOD) in erythrocytes to assess the degree of tissue oxidative stress. RESULTS: Significantly more severe colitis, including necrosis, ulceration, and hemorrhage, was seen in colonic biopsies of rats with colitis when iron was supplemented. This pathology was attenuated when iron was given in combination with 5-ASA and/or lycopene. There was no significant benefit from adding Beta-carotene. CONCLUSIONS: Iron supplementation can amplify the inflammatory response and subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through the generation of secondary toxic oxidants. Simultaneous treatment with 5-ASA and/or lycopene minimizes the potential hazard of iron. Therefore, we suggest giving iron supplementation with 5-ASA or lycopene or both.

Animals↗

Identification and characterization of linear B-cell epitopes of beta-globulin, a major allergen of sesame seeds.

BACKGROUND: The increased consumption of foods containing sesame seeds is paralleled by an increase in reported sesame-induced allergic reactions. OBJECTIVE: This study aimed at identifying and characterizing the linear B-cell epitopes of the 14-kd beta-globulin, the major allergen of sesame seed. METHODS: A peptide containing 71 amino acids (peptide B) was previously identified by us as the IgE-binding region on beta-globulin. To determine the amino acid sequence of the IgE-binding sites on peptide B, we synthesized overlapping peptides 20 and 10 amino acid residues long that span the entire length of peptide B, which were offset from each other by 10 and 2 amino acid residues, respectively. Sera from 20 subjects given diagnoses of allergy to sesame beta-globulin served to identify the epitopes by using the dot-blot test. RESULTS: At least 9 different IgE-recognition sites were identified on peptide B. Three of them, numbers 2, 3, and 13 (corresponding to amino acids 46-55, 48-57, and 76-86, respectively, in the beta-globulin sequence), appeared to be immunodominant IgE-binding epitopes. Also, these peptides were best recognized in terms of intensity of response. There was no obvious sequence motif shared by the 9 different IgE-binding epitopes of beta-globulin. However, approximately 60% of the amino acids represented in the epitopes are hydrophobic residues. CONCLUSION: Identification of the IgE-binding epitopes might provide a better understanding of the functional role the allergens play in the disease and might have implications for immunodiagnosis and probably immunotherapy.

Adolescent↗

Vitamin A deficiency aggravates rotavirus infection in CD-1 mice through extensive involvement of the gut.

Rotavirus (RV) is one of the leading causes of life-threatening viral gastroenteritis in infants and animals. More than 100 million children live in endemic areas where they are at risk of rotavirus infection. In the western world, rotavirus is usually a self-limiting disease that involves no major sequelae; however, in the developing world it often leads to morbidity and mortality. One of the major components influencing the prognosis of rotavirus-infected children is their nutritional status. The prevalence of vitamin A deficiency in developing countries, where RV infection can be fatal, encompasses up to 40% of preschool children. We hypothesized, therefore, that vitamin A deficiency in an animal model would aggravate the course of rotavirus disease. CD-1 mice were infected with RV and fed either vitamin A-sufficient or vitamin A-deficient diets. Histological components of the small intestine and colon, stool samples from which rotavirus was recovered, and vitamin A levels were examined. Flattening of the villi along the duodenum was observed in both rotavirus-infected and non-infected vitamin A-deficient mice. Maximal effect was obtained with a combination of vitamin A deficiency and RV infection. The colon of vitamin A-deficient, infected mice displayed a significantly (p < 0.05) smaller glandular area and higher level of mucin, and viral excretion in the stool became significantly (p < 0.01) increased and lasted longer than in controls. We conclude that vitamin A deficiency aggravates the course of RV infection through both small intestinal and colonic damage.

Animals↗

Dietary iron affects inflammatory status in a rat model of colitis.

Iron deficiency anemia is a common feature in inflammatory bowel disease, and oral supplementation is one of the mainstay therapies. However, there is some concern that oral iron supplementation may lead to oxidative stress and exacerbation of inflammation. Our objective was to study the effect of severely deficient, moderately deficient, normal and high iron status on oxidative stress and the course of inflammation in a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The rats were randomly assigned to receive the low-iron diet for 3 (moderately iron-deficient group, n = 16) or 5 (severely iron-deficient group, n = 16) wk, the normal iron diet for 2 wk (normal iron group, n = 16) or the high-iron diet for 2 wk (high-iron group, n = 16). Malondialdehyde concentration, electroparamagnetic resonance measurement, myeloperoxidase activity, and histological analysis were used to evaluate oxidative stress. Noncolitic rats in the high-iron group had higher oxidative stress parameters than those in the other groups. The induction of colitis resulted in severe inflammatory changes in the high-iron and severely iron-deficient groups, and produced higher histological scores in the colon of the normal and high-iron groups. Iron overload, oxidative stress, and inflammation were lower in the moderately iron-deficient group compared with the other 3 groups. In conclusion, we suggest that low rather than normal or high iron supplementation should be considered for the treatment of iron deficiency in inflammatory bowel disease.

Animals↗

Beta-carotene bioavailability from differently processed carrot meals in human ileostomy volunteers.

BACKGROUND: Carotenoids contribute to the beneficial effects of fruits and vegetables consumption; however, the bioavailability of these compounds from fresh or processed foods is not well established. AIM OF THE STUDY: We evaluated the bioavailability of beta-carotene (15 mg) from a single meal composed of cooked, pureed carrots and compared it to raw, chopped carrots. METHODS: Test meals were given to overnight-fastedileostomy volunteers (n = 8) along with skimmed-milk yogurt containing 40 g of added sunflower oil. Blood and complete ileal effluent samples were collected over a 24 h period. Samples were solvent-extracted and the beta-carotene content measured by HPLC. RESULTS: Kinetics of excretion of cis and trans beta-carotene were similar. More beta-carotene was absorbed from puree as compared to raw carrots. Carotenoid mass-balance calculations indicated that 65.1 +/- 7.4% of the beta-carotene was absorbed from cooked pureed carrot meals, vs. 41.4 +/- 7.4 % from raw, chopped carrot meals. Gastrointestinal transit parameters did not differ significantly among the volunteers. As expected, the calculated lag phase was five times longer for raw vs. cooked carrots. Mean t-end, t-1/2 and rate of mass transit resulted in similar values for both raw and cooked carrot meals. A moderate response in carotenoid plasma profile was observed for cooked carrot test meals. CONCLUSIONS: Significantly more beta-carotene was absorbed from meals containing cooked, pureed carrots than from meals containing the raw vegetable. Moderate carotenoid plasma response was detected within 6 h following the administration of cooked processed carotenoid-containing single meal.

Adult↗

Ethiopian-born and native Israeli school children have different growth patterns.

OBJECTIVE: Nutrition status of preschool children in Azezo, North West Ethiopia, and Ethiopian-born and native Israeli children aged 7 to 11 y and 12 to 15 y was studied. The aim of the study was to determine the growth patterns of immigrant children after changes in their nutritional habits. METHODS: The Ethiopian-born and native school children were recruited from a caravan-dwelling site and a boarding school and from a town adjacent to the caravan site and a boarding school, respectively. RESULTS: Weight for age was lower than -2 standard deviations of the Z score in 40.5%, 55.6%, 31.9%, and 61% of children aged 1 to 24, 25 to 36, 37 to 48, and 49 to 60 mo, respectively. Similarly, 18.9%, 59.3%, 39.1%, and 19.5% of children aged 1 to 24, 25 to 36, 37 to 48, and 49 to 60 mo had a height for age lower than -2 standard deviations of the Z score. The Ethiopian-born boys aged 7 to 11 y had lower body weight (P < 0.03), mean arm muscle circumference, plasma transthyretin and magnesium (P < 0.0001), and higher triceps skinfold thickness (P < 0.01) compared with the controls. Similarly, the Ethiopian-born girls had lower body weight (P < 0.006), weight-to-height ratio (P < 0.02), mean arm muscle circumference and plasma transthyretin, calcium, and magnesium (P < 0.0001), and higher triceps skinfold thickness (P < 0.0001) than their Israeli counterparts. Weight, weight-to-height ratio, mean arm muscle circumference, plasma calcium and magnesium (P < 0.0001), and transthyretin (P < 0.01) were lower and triceps skinfold thickness (P < 0.0001) was higher in the Ethiopian-born boarding school children than in the native Israelis of the same age range. CONCLUSIONS: The Azezo study confirmed that malnutrition-induced developmental impairment in preschool children is a major problem in Ethiopia. It is a manifestation of a rural economic and educational poverty and cannot be eradicated by palliative short-term nutritional programs. Although ethnicity and prenatal and postnatal malnutrition may have contributed, an insufficiency or imbalance of vital nutrients appeared to be the determinant factor for the lower relative growth of the Ethiopian-born children. The children from Ethiopia may have a propensity to avoid certain foods because of digestive intolerance or early childhood dietary habituation. Parental financial constraint may have been a factor in the younger group. These findings have implications for nutrition and welfare policies for children emigrating from developing countries.

Adolescent↗

The pattern of sesame sensitivity among infants and children.

Recently, we found sesame to be a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE-mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients 'outgrew' their allergy within 1-2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut - a major cause of severe food allergic reactions.

Angioedema↗

The significance of routine duodenal biopsies in pediatric patients undergoing upper intestinal endoscopy.

GOALS: To determine the significance of performing routine duodenal biopsies during upper intestinal endoscopy in a pediatric population and to evaluate their contribution to the overall diagnosis. BACKGROUND: Performing duodenal biopsy during every upper endoscopy regardless of the indication for endoscopy and the macroscopic findings, is a controversial topic. Advocates of performing routine biopsies argue that unexpected pathology such as villous atrophy, may have significant clinical implications. Opponents argue that the yield of performing a biopsy on an apparently normal mucosa is low. STUDY: Duodenal biopsies, routinely taken from 201 pediatric patients during upper endoscopy over a 26-month period were retrospectively reviewed. Duodenal biopsies taken during this period for suspected mucosal lesions were not included in the analysis. Indications for endoscopy included suspected peptic disease, gastroesophageal reflux, unexplained vomiting, abdominal pain, iron deficiency anemia and Crohn disease. RESULTS: Of the 201 sets of biopsies reviewed, 159 (79.1%) were normal, 7 had insufficient material for evaluation and 35 (17.4%) carried abnormalities that included: 10 Giardia lamblia (4.9%), 13 mild chronic inflammation (6.5%), and 8 increased intraepithelial lymphocytes (3.9%). Two biopsies showed mixed acute and chronic inflammation, 1 showed lymphatic dilatation and 1 had a mild mucosal lesion. The risk for microscopic pathology in the duodenum was higher when Helicobacter pylori was present in the gastric biopsy (25.98% vs. 12.16% P < 0.02). The negative predictive value of a normal appearing duodenal mucosa was 81.5%, implying that a normal appearing mucosa does not rule out pathology. No complications were encountered in our series. CONCLUSION: We suggest that the inclusion of routine duodenal biopsies as part of upper endoscopy in pediatric patients should be considered favorably. This practice may yield additional pathologic findings that otherwise could have been missed. It should be done regardless of the indication for endoscopy or the gross appearance of the mucosa. This practice does not increase the risk of the procedure.

Adolescent↗

Adult height and weight of breast-fed and bottle-fed Israeli infants.

BACKGROUND: Breast-fed infants grow more slowly than bottle-fed infants. This growth deceleration sometimes alarms health care personnel to the point of considering other forms of nutrition. OBJECTIVES: To evaluate the final adult anthropometric outcome associated with breast or formula feeding during infancy. DESIGN: Height and weight data were collected from eight well-baby clinics representing various ethnic origins, lifestyles, and socioeconomic backgrounds. Children were measured every 1 to 2 months for the first 6 months, every 3 months until 2 years of age, and yearly thereafter, until they reached their final height. Longitudinal data were collected from 1960 healthy children (961 boys). Overall, 613 of the children were breast fed for 1 year and 218 for 6 months. RESULTS: The magnitude of the decline in Z scores of breast-fed vs. bottle-fed infants, between birth and 1 year of age was not as great for height as for weight -0.2 and -0.3 respectively, and disappeared at 2 years of age. The weight for height decreased between birth and the end of the first year in breast-fed children by 0.3 (Z score). Children switched to bottle feeding exhibited a growth spurt. However, there was no difference in the final heights or weights of breast-fed children compared with bottle-fed children 165.3 +/- 6.2 (n = 134) versus 164.9 +/- 6.4 (n = 195) in females, respectively, and 175.3 +/- 6.8 (n = 122) versus 175.8 +/- 7.1 (n = 162) in males, respectively. Adult obesity in this sample population (n = 637) was correlated with maternal obesity. Maternal BMI SD correlated with offspring BMI SD at 18 years of age (r = 0.873, P < 0.001) but not with breast feeding. Adult BMI was similar between the breast-fed and bottle-fed groups. CONCLUSIONS: Despite their slower growth rate, breast-fed children reach the same final height as bottle-fed children. Breast-fed infants should be monitored according to specifically designed growth charts. Obesity in adult life is correlated with factors not related to breast feeding.

Body Height↗

Oral cancer cells differ from normal oral epithelial cells in tissue like organization and in response to lycopene treatment: an organotypic cell culture study.

We established distinctive monolayer and organotypic cell culture techniques to assess possible differences in cross-talk and spatial and structural organization of oral cancer cells compared with normal oral cells and also to evaluate possible differential responses of the cells to carotenoids. In monolayers, we investigated the effect of lycopene on the proliferation of an established oral cancer cell line, KB-1, and compared it with a primary cell line obtained from normal oral mucosa. Lycopene exerted a significant inhibitory effect on KB-1 cell proliferation inducing a dose-dependent downregulation of proliferating cell nuclear antigen (PCNA) associated with upregulation of connexin-43 (Cx-43) expression, whereas in the normal oral mucosal cells lycopene did not affect either PCNA expression, which was very low, or the expression of Cx-43, which was basically very high. Lycopene significantly inhibited the formation of colonies induced by the carcinogen 3-methylcholanthrene (MCA) on normal oral cells and almost completely abrogated the hyperplastic effect induced by MCA. KB-1 cells and normal oral epithelial cells in the organotypic cell culture method differed in their stratification and intercellular adhesion patterns as well as in the expression profile of cytokeratins, vimentin, and Cx-43. Lycopene induced Cx-43 expression in KB-1 cells grown by the organotypic raft method, similar to KB-1 cells grown as monolayers. We conclude that lycopene is a promising chemopreventive, pro-differentiating, and anticarcinogenic agent. No adverse effects of lycopene were detected in normal cells cultured in either monolayer or organotypic systems.

Anticarcinogenic Agents↗

Plasma and buccal mucosal cell response to short-term supplementation with all trans-beta-carotene and lycopene in human volunteers.

Despite interest in the health-beneficial role of carotenoids little is known about the specific storage metabolism and mechanisms involved in various target tissues. The aim of the study was to search for a relatively simple non-invasive method to detect and determine the cellular effects of supplemented dosage of beta-carotene and lycopene to peripheral tissues such as the buccal mucosa in relation to the plasma concentrations. Subjects (30) were allocated into five different subgroups of 6 volunteers. The change in concentration of all-trans-beta-carotene and lycopene in plasma and in buccal mucosal cells was measured in groups of volunteers supplemented with either 15 mg, 30 mg or placebo capsules in a randomised double blind study for a period of 7 days. With the exception of supervised high fat (40 g carotenoid free sunflower oil) breakfasts and capsule ingestion the volunteers ate their habitual diets. Plasma lycopene and beta-carotene concentrations were determined at baseline and following one week of capsule ingestion. In all the supplemented groups the plasma carotenoid levels were significantly higher than in the placebo group indicating absorption of the supplement. Carotenoid concentrations, expressed per unit protein, assayed in buccal mucosal cells before (at baseline) and at the end of the study were found to be significantly higher in the groups supplemented at 30 mg/d, of either carotenoid as compared to the 15 mg/d or placebo supplemented groups. We conclude that buccal mucosal cells respond readily to changes in plasma beta-carotene and lycopene concentration. These observations suggest that dietary carotenoids are quickly incorporated into rapidly turning over mucosal tissues. It is not clear if the change in carotenoid content of the plasma is reflected in existing cells or only in those concurrently produced during the elevated plasma concentration. If desquamated buccal mucosal cells reflect habitual plasma carotenoid concentration then it is not an appropriate tissue for the measurement of acute changes.

Analysis of Variance↗

Pyrrolidine dithiocarbamate protects against thioacetamide-induced fulminant hepatic failure in rats.

BACKGROUND/AIMS: Reactive oxygen species and nuclear factor kappa B (NF-kappaB) activation have been implicated in the pathogenesis of cell injury in experimental models of liver damage. The aim of the present study was to examine whether pyrrolidine dithiocarbamate (PDTC), an anti oxidant and inhibitor of NF-kappaB activation, would prevent hepatic damage induced in a rat model of thioacetamide (TAA)-induced liver failure. METHODS: Fulminant hepatic failure was induced in the control and treatment groups by two intraperitoneal injections of TAA (either 300 or 400 mg/kg) at 24-h intervals. In the treatment groups, rats were treated also with PDTC (60 mg/kg/24 h, i.p.), initiated 24 h prior to TAA. RESULTS: Liver enzymes, blood ammonia, and hepatic levels of thiobarbituric acid reactive substances (P<0.001) and protein carbonyls (P<0.05) were significantly lower in rats treated with PDTC compared to TAA only. Liver histology and the survival rate in the PDTC-treated rats were also improved (P<0.01 compared to TAA only). NF-kappaB activation, 2 and 6 h after TAA administration, was inhibited by PDTC. CONCLUSIONS: In a rat model of fulminant hepatic failure, the administration of PDTC attenuated liver damage and improved survival. This effect may be due to decreased oxidative stress and inhibition of NF-kappaB activation.

Ammonia↗