methylcellulose and Body-Weight

It should be obvious from the foregoing discussion that, at the present time, there is not an acceptably safe and effective pharmacological treatment for obesity. This patent inadequacy of present drug regimens has spawned the investigation into the diverse pharmacological approaches reviewed in this paper as well as investigation into the intestinal bypass operation (see Chapter 10). We feel that the eventual, safe and effective therapy for obesity will come from the pharmacological realm. Glucose-blocking drugs, growth hormone analogues, and hydroxycitrate are but three of the potentially safe and effective approaches to the problem for the future. It will be truly fascinating to watch the development in the treatment of obesity and, specifically, the pharmacological treatment for this problem over the next five to ten years.

Topics: Amphetamines; Appetite Depressants; Body Weight; Cardiovascular System; Central Nervous System; Chorionic Gonadotropin; Citrates; Dinitrophenols; Glucose; Growth Hormone; Humans; Lipid Mobilization; Methylcellulose; Obesity; Organomercury Compounds; Oxygen Consumption; Phenformin; Placental Lactogen; Progesterone; Receptors, Adrenergic; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Triiodothyronine

1. The present study was undertaken to determine the effects of arginine, soy isoflavone (ISF) and hydroxypropylmethylcellulose (HPMC) on obesity in broiler breeder hens. 2. A total of 320 Cobb 500 hens, 45 weeks of age, were assigned to 64 floor pens. The experiment was conducted as a completely randomised design in a factorial arrangement (2 × 2 × 2 × 2) with 4 replicates of 5 hens in each pen. Factors included two concentrations of HPMC (0 and 1%), two concentrations of arginine (8.4 and 12 g/kg), two concentrations of ISF (zero and three times more than that present in basal diets) and two contents of energy (11.7 and 14.6 MJ/kg). Performance criteria and blood characteristics of hens were measured during the experimental period. Expression of genes involved in lipid metabolism was determined in the liver at 55 weeks of age. 3. Hens given high-energy diets showed increased BW (body weight), ovary weight and abdominal fat pad and enhanced plasma glucose, triglyceride (TG), cholesterol, haemoglobin, haematocrit and low lymphocyte percentages. The expression of malic enzyme, peroxisome proliferator-activated receptor-α (PPARα), peroxisome proliferator-activated receptor-γ (PPARγ) and inducible nitric oxide (iNOS) increased and sterol regulatory element binding protein-1c (SREBP1c) decreased with increasing energy content of diets. Arginine addition decreased TG, cholesterol and A1-c haemoglobin concentration and increased PPARα, PPARγ and iNOS expression. Inclusion of ISF and HPMC decreased BW, egg weight, plasma TG, cholesterol and increased egg production and also enhanced PPARγ and iNOS expression. Significant interactions were observed between energy concentration and ISF and HPMC on BW. 4. The results of the current study revealed that ISF, HPMC and arginine have beneficial effects on controlling the metabolism of obese broiler breeder hens and using a mix of these products minimises the harmful effects of obesity.

Topics: Animal Feed; Animals; Arginine; Avian Proteins; Blood Chemical Analysis; Body Weight; Chickens; Diet; Dietary Supplements; Fatty Acids; Female; Glycine max; Hypromellose Derivatives; Isoflavones; Lipid Metabolism; Liver; Methylcellulose; Obesity; Ovum; Oxidation-Reduction; Poultry Diseases; Real-Time Polymerase Chain Reaction

Little is known about the relative effects of fermentable fiber (FF) vs. nonfermentable fiber (NFF) on energy regulation in humans. We compared 27 +/- 0.6 g/d supplements of FF (pectin, beta-glucan) and NFF (methylcellulose) for their ability to decrease ad libitum energy intake (EI) and hunger, increase satiety and cause spontaneous body weight and fat losses. Men and women (n = 11) aged 23-46 y, BMI 20.0-34.4 kg/m2, consumed first NFF and then FF for 3 wk each, with a 4-wk washout period between phases. Daily satiety assessed with analog scales was higher with NFF than FF (60.7 +/- 1.0 vs. 57.7 +/- 0.8 mm, P = 0.01). However, there were no differences in reported EI (NFF < FF by 7%, P = 0.31, NFF < baseline by 9.5%, P = 0.11), body weight (NFF 0.13 kg, P = 0.73; FF 0.13 kg, P = 0.60) or fat percentage (NFF -0.3%, P = 0.56; FF -0.1%, P = 0.66) within either phase. In contrast to findings in animals, NFF was more, rather than less satiating than FF, and use of neither NFF nor FF preparations was associated with body weight or fat loss. These pilot results suggest no role for short-term use of FF and NFF supplements in promoting weight loss in humans consuming a diet ad libitum.

Topics: Adult; Body Mass Index; Body Weight; Diet; Dietary Fiber; Dietary Supplements; Energy Intake; Female; Fermentation; Glucans; Humans; Hunger; Male; Methylcellulose; Middle Aged; Pectins; Pilot Projects; Satiation

Hydroxypropylmethylcellulose (HPMC) is a food gum that shares certain characteristics, such as high viscosity, with soluble fibers. In this trial, the safety and cholesterol-lowering efficacy of HPMC consumed with and between meals was evaluated in free-living male volunteers with mild-to-moderate hypercholesterolemia. After a 14-d baseline period, men (n = 51) with LDL cholesterol between 3.36 and 4.91 mmol/L and triglycerides <3.95 mmol/L were randomly assigned to consume 5.0 g/d HPMC in 240 mL of orange drink, taken either with or between meals, for a 2-wk treatment period. In the Between Meals group, total cholesterol was reduced by 8.0% vs. baseline in wk 1 of treatment (P < 0.05) and 5.1% in wk 2 (P < 0.01). LDL cholesterol concentrations fell by 12.0 and 7.7% (P < 0.01). In the With Meals group, reductions were 9.5 and 8.3% for total cholesterol, and 12.5 and 12.8% for LDL cholesterol (wk 1 and 2, respectively, P < 0.01). In both groups, HDL cholesterol decreased by approximately 5% during wk 1 of treatment (P < 0.01), but the wk 2 concentrations were not significantly different from baseline. There were no significant differences between groups in lipid responses, although there was a trend for a smaller LDL cholesterol-lowering effect during wk 2 of treatment in the Between Meals group (P < 0.06). Gastrointestinal-related adverse experiences (mostly mild) were twice as common among participants who ingested HPMC with meals (P < 0.05). These results suggest that HPMC has a lipid-lowering effect, which may be more consistent when taken with meals.

Topics: Adult; Anticholesteremic Agents; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Digestive System; Fasting; Feeding Behavior; Humans; Hypercholesterolemia; Hypromellose Derivatives; Lipids; Male; Methylcellulose; Molecular Weight; Viscosity

Diet influences host metabolism and intestinal microbiota; however, detailed understanding of this tripartite interaction is limited. To determine whether the nonfermentable fiber hydroxypropyl methylcellulose (HPMC) could alter the intestinal microbiota and whether such changes correlated with metabolic improvements, C57B/L6 mice were normalized to a high-fat diet (HFD), then either maintained on HFD (control), or switched to HFD supplemented with 10% HPMC, or a low-fat diet (LFD). Compared to control treatment, both LFD and HPMC reduced weight gain (11.8 and 5.7 g, respectively), plasma cholesterol (23.1 and 19.6%), and liver triglycerides (73.1 and 44.6%), and, as revealed by 454-pyrosequencing of the microbial 16S rRNA gene, decreased microbial α-diversity and differentially altered intestinal microbiota. Both LFD and HPMC increased intestinal Erysipelotrichaceae (7.3- and 12.4-fold) and decreased Lachnospiraceae (2.0- and 2.7-fold), while only HPMC increased Peptostreptococcaceae (3.4-fold) and decreased Ruminococcaceae (2.7-fold). Specific microorganisms were directly linked with weight change and metabolic parameters in HPMC and HFD mice, but not in LFD mice, indicating that the intestinal microbiota may play differing roles during the two dietary modulations. This work indicates that HPMC is a potential prebiotic fiber that influences intestinal microbiota and improves host metabolism.

Topics: Animals; Bacteria; Biodiversity; Body Weight; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fiber; Hypromellose Derivatives; Intestines; Metabolome; Metagenome; Methylcellulose; Mice; Mice, Inbred C57BL; Phylogeny; Prebiotics; RNA, Bacterial; RNA, Ribosomal, 16S

The effect of hydroxyethyl methylcellulose (HEMC) with different viscosities on the glucose metabolism and antioxidative defense system in high fat-fed mice was investigated. The mice were randomly divided into five dietary groups: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with high viscosity (HF-HV), moderate viscosity (HF-MV), and low viscosity (HF-LV) HEMC fibers. After 6 weeks, the HF group showed a marked increase in body weight gain, body fat, blood glucose concentration, insulin level, and erythrocyte lipid peroxidation rate relative to the NC group. However, supplementation of HEMC in the diet suppressed these high fat-induced hyperglycemia and oxidative stress through enhancement of the activities of hepatic glucokinase and antioxidant enzymes. The hypoglycemic and antioxidative effects increased with increased viscosity of the HEMC consumed. These results illustrate that HEMC with high viscosity may be useful in the management of high fat diet-induced hyperglycemia and oxidative stress.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Dietary Fats; Enzymes; Hypoglycemic Agents; Insulin; Lipid Peroxidation; Male; Methylcellulose; Mice; Mice, Inbred C57BL

To investigate the effect of hydroxypropyl methylcellulose (HPMC) on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model under a high-fat diet regimen..  Obese male C57BL/6J (B6) mice were fed either a high-fat (60% kcal), low-fat (10% kcal), or high-fat diet plus HPMC (4% and 8%) for 5 weeks. Body, mesenteric adipose, and liver weights were determined at the end of the study. In addition, plasma cholesterol, insulin, glucose, adiponectin, and leptin were analyzed to determine the effects of HPMC. Hepatic and fecal lipids were measured to determine the effect of HPMC on lipid absorption and metabolism.. Supplementation of the high-fat diet with 4% and 8% HPMC resulted in significant weight loss in obese B6 mice. Furthermore, significant decreases were seen in adipose (30%-40%), liver weights (15%-26%), and concentrations of plasma cholesterol (13%-20%) and hepatic lipids (13%-36%). Supplementation with 8% HPMC led to significant improvements in glucose homeostasis and leptin concentrations. Reductions in plasma cholesterol, glucose, and insulin levels were strongly correlated with reduced leptin concentrations. Moreover, increases in fecal secretion of total bile acids, sterols, and fats indicated altered fat absorption when HPMC was incorporated in the diet.. The data indicate that HPMC not only reduces body weight, but also normalizes the metabolic abnormalities associated with obesity and suggest that the effects of HPMC on glucose and lipid homeostasis in B6 mice are mediated by improvements in leptin sensitivity resulting from reduced fat absorption.

Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Fats; Hypromellose Derivatives; Insulin; Leptin; Liver; Male; Methylcellulose; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Random Allocation; Regression Analysis; Weight Loss

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

Topics: Animals; Blood Chemical Analysis; Body Weight; Eating; Excipients; Female; Histocytochemistry; Male; Methylcellulose; Organ Size; Polysorbates; Rats; Rats, Wistar; Triglycerides; Urinalysis

2-Amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was synthesized by reacting 2-amino-5-methylphenol with bovine hemolysates. Because Phx is a phenoxazine derivative like actinomycin D, we examined its effects on the proliferation of the human leukemia cell lines K562, HL-60, and HAL-01. Phx inhibited proliferation and induced apoptosis in all of the leukemia cell lines we tested, in a dose-dependent manner. We further investigated the antitumor effect of this compound on HAL-01-bearing nude mice. Treatment with Phx markedly reduced the tumor growth rate in the experimental group, as compared with the control group. Moreover, Phx was found to have few adverse effects on weight loss and WBC count. In addition, we examined the effects of Phx on human normal hematopoietic progenitor cells by a clonogenic assay, and we observed less suppression of normal progenitor cells than of leukemic progenitors. These results suggest that Phx may be used to treat patients affected by different types of leukemia.

Topics: Animals; Antineoplastic Agents; Apoptosis; Body Weight; Cell Division; Dose-Response Relationship, Drug; HL-60 Cells; Humans; K562 Cells; Leukemia; Methylcellulose; Mice; Mice, Inbred BALB C; Oxazines; Time Factors; Tumor Cells, Cultured

The toxicity of the lowest viscosity grade of hydroxypropyl methylcellulose (HPMC) that is currently commercially available was investigated by means of a three-month repeated oral administration study in male and female Crj:CD (SD) IGS rats at doses of 505, 1,020 and 2,100 mg/kg/day. Body weights of males and females in the 2,100 mg/kg group were lower than those of the control group on and after day 28 of administration, but the differences were not statistically significant. The degree of suppression of body weight gain in males was higher than that in females. This tendency was similar to the results in other toxicity studies of HPMC that have been reported. Males in the 2,100 mg/kg group showed a tendency (not significant) for decreased food consumption and urine volume. Examinations of general signs, hematology, blood chemistry, ophthalmology, absolute and relative organ weights, autopsy and histopathology revealed only a few, apparently coincidental, statistically significant differences from the control, and no evidence of any dose-dependent changes was found. It was concluded that the lowest viscosity grade of HPMC showed extremely low toxicity under the conditions of this study, as has been found for higher viscosity grades.

Topics: Administration, Oral; Animals; Blood Chemical Analysis; Body Weight; Eating; Eye; Female; Hypromellose Derivatives; Male; Methylcellulose; Organ Size; Rats; Sex Factors; Urine; Viscosity

Skin sensitization and photosensitization tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, were conducted using guinea pigs. An aqueous dispersion of HM-HPMC (3 w/v %) was applied in the tests. Skin reaction was not observed in any animal in the HM-HPMC-treated group or control group. In the photosensitization test, no skin reaction was found in any animal in the test-preparation group or the control group. It was concluded that HM-HPMC dispersion does not exhibit skin sensitizing or photosensitizing activity under the condition of this test.

Topics: Adjuvants, Pharmaceutic; Administration, Topical; Animals; Body Weight; Female; Guinea Pigs; Hypromellose Derivatives; Light; Methylcellulose; Photosensitivity Disorders; Skin; Skin Tests; Solubility

A six-month repeated-dose dermal toxicity study followed by a 30-day recovery test of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, was conducted using rats. Aqueous paste of HM-HPMC was applied to the skin of rats once daily at dose levels up to 60 mg/kg/day, which was the highest dose that could be administered. Items checked included general signs, urinalysis, hematology, ophthalmology, and histopathology. One rat died during the administration period owing to a malignant tumor in the hemopoietic system, which was not attributed to the test substance. Statistically significant differences were found in some test results, but those were not dose-dependent and were considered to be incidental or spontaneous. It was concluded that the test substance was not toxic upon chronic dermal administration at dose levels up to 60 mg/kg/day.

Topics: Administration, Cutaneous; Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Cell Count; Body Weight; Eating; Female; Hypromellose Derivatives; Male; Methylcellulose; Rats; Rats, Sprague-Dawley; Time Factors; Urinalysis

Kelce and Wilson (J. Mol. Med. 75, 198-207, 1997) have suggested that dosing chemicals to newly weaned male rats for 1 month may yield a useful assay for antiandrogens. This suggestion was supported by reference to unpublished data on the antiandrogen vinclozolin which indicated reductions in the weight of accessory sex organs. The necessity for dosing during the full approximately 30 days of the protocol was not justified. An evaluation of this protocol has commenced by the dosing of vinclozolin, cyproterone acetate, and anastrozole daily to newly weaned male rats for 3, 7, or 14 days. No changes were observed in accessory sex organs when vinclozolin or anastrozole was dosed for 3 days. Significant changes were observed in the absolute and relative weight of all of the sex accessory organs for rats dosed for 7 or 14 days with cyproterone acetate. The effects produced by vinclozolin and anastrozole when dosed for 7 or 14 days varied according to the duration of exposure with the main effects on the accessory sex organs being seen after 14 days of dosing. The effects produced after 7 days of dosing with vinclozolin or anastrozole in arachis oil had resolved 10 days after the last of the seven doses. Data are presented using either hydroxy propyl methyoxycellulose (HPMC) or arachis oil as vehicle, the former being recommended for general use. These preliminary results are encouraging, and the evaluation of the second 2 weeks of the suggested 30-day protocol is proceeding. Concurrent control data indicate that the relative weight of the liver, testes, and epididymides increases over the first 14 days post-weaning, while those of the kidney, the seminal vesicles, and prostate decrease. These changes in relative tissue weight were much less than the increase in relative weight of the uterus observed in female animals at puberty. That indicates that successful use of a final version of this assay will depend on access to inhouse control tissue weight data and the use of appropriate animal group sizes. These preliminary data are presented to reduce duplication of effort in this rapidly expanding area of toxicology.

Topics: Anastrozole; Androgen Antagonists; Animals; Body Weight; Cyproterone Acetate; Drug Evaluation, Preclinical; Endocrine System Diseases; Female; Lactose; Male; Methylcellulose; Nitriles; Organ Size; Oxazines; Oxazoles; Rats; Rats, Inbred Strains; Toxicology; Triazoles; Uterus; Weaning

Enteroglucagon is a collective term for a small family of peptides derived from proglucagon by post-translational processing in the L-cells of the distal small intestine and colon. There is evidence that it inhibits gastric secretion, and high levels of enteroglucagon occur in plasma during intestinal adaptation, which suggests that it may also function as a trophic factor for the intestine. Certain types of soluble non-starch polysaccharide (dietary fiber) stimulate the release of enteroglucagon in rats but the mechanism is unknown. In this study we explored the importance of the viscosity and fermentability of nonabsorbed carbohydrates as determinants of plasma enteroglucagon and mucosal cell proliferation in the distal ileum of rats. Replacement of cellulose (10 g/kg) with guar gum in a semisynthetic diet led to a prompt and sustained rise in plasma enteroglucagon concentrations. Our initial hypothesis that this was a consequence of delayed nutrient absorption was disproven by the fact that hydroxypropylmethylcellulose (HPMC), a viscous but nonfermentable polysaccharide, had no effect on plasma enteroglucagon under the same conditions. In contrast, the nondigestible disaccharide lactitol led to a prolonged rise in plasma enteroglucagon, similar to that observed with guar gum. Lactitol is nonviscous, but highly fermentable, and we conclude that fermentable carbohydrate is an important stimulus for the release of enteroglucagon under our experimental conditions. There was no evidence that enteroglucagon released by this mechanism exerted trophic effects on the distal small intestinal mucosa.

Topics: Animals; Body Weight; Cathartics; Cell Division; Cellulose; Colon; Dietary Carbohydrates; Dietary Fiber; Eating; Fermentation; Galactans; Glucagon-Like Peptides; Hypromellose Derivatives; Ileum; Intestinal Absorption; Intestinal Mucosa; Male; Mannans; Methylcellulose; Microvilli; Plant Gums; Rats; Rats, Wistar; Sugar Alcohols; Viscosity

The attribute(s) of soluble dietary fibers responsible for cholesterol lowering is currently uncertain. A series of experiments were conducted in which viscosity and fermentability was assessed independently for their effect on plasma and liver cholesterol concentration. Hamsters were divided into four dietary groups and fed diets containing 0.12% cholesterol and 5% fiber as high viscosity hydroxypropyl methylcellulose (HV-HPMC group), low viscosity hydroxypropyl methylcellulose (LV-HPMC group), high viscosity guar gum (HV-GG group) or low viscosity guar gum (LV-GG group). Hydroxypropyl methylcellulose is essentially nonfermentable, whereas guar gum is highly fermentable. Plasma cholesterol concentrations at 3, 6 and 11 wk and liver cholesterol concentrations at 6 and 11 wk were significantly lower in the HV-HPMC group relative to the LV-HPMC group (P < 0.05). Intestinal content viscosities of the LV-HPMC and HV-GG groups were similar; consequently, these two groups were compared to examine the independent effect of fermentation. Plasma and liver cholesterol were significantly lower in the HV-GG group compared with the LV-HPMC group at 6 wk (P < 0.05), but not at 3 or 11 wk. Hepatic sterol synthesis rates were not affected by any of the diets. This study shows that greater viscosity of intestinal contents is strongly associated with cholesterol reduction, but that the contribution of fiber fermentation remains uncertain.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Body Weight; Cholesterol; Cricetinae; Dietary Fiber; Eating; Fermentation; Galactans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Liver; Male; Mannans; Mesocricetus; Methylcellulose; Plant Gums; Viscosity

Single-dose toxicological studies of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether) were conducted. A dispersion of HM-HPMC was administered to rats orally or by dermal application at doses up to 900 mg/kg. After the oral administration, the mean body weight of the 900 mg/kg group on the first day after administration was slightly but significantly lower (P less than 0.05) than that of the control group, and one rat had loose stools at 30 min. after the administration. No other abnormalities were noted. In the case of dermal application, no abnormalities were observed. No rats died, and no abnormalities in their organs were found by either route. In conclusion, there was no observed toxicity of HM-HMPC after oral or dermal administration at single dose up to 900 mg/kg under the conditions of these studies.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Body Weight; Female; Hypromellose Derivatives; Male; Methylcellulose; Molecular Weight; Rats

Lactating female and neonatal Fischer 344 rats were given water containing [14C]methylcellulose, a nonabsorbed marker, over a 24-hr interval on Days 13, 15, 18, 21, 24, and 27 postpartum. The amount of water consumed was calculated based on the 14C activity recovered in the feces and gastrointestinal tract. Maternal water consumption during the first 28 days postpartum, when expressed as g/kg/day, averaged 2.5 times the level consumed by nonlactating female rats. Maternal water consumption peaked on Day 21 postpartum at 3.3 times the level measured in nonlactating female rats of comparable age. Neonatal water consumption began on Day 18 postpartum and by Day 28 postpartum was 1.9 times the level observed in nonlactating females. Average neonatal water consumption between Days 21 and 28 postpartum was 1.3 times the level for nonlactating female rats. These data indicate that when the test material is administered via the drinking water the dose levels received by the maternal and neonatal rats have been routinely underestimated, and that conclusions concerning the dose-response relationship or increased sensitivity during this period must be tempered by these results.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Drinking; Female; Lactation; Male; Methylcellulose; Pregnancy; Rats; Rats, Inbred F344

The acute toxicity (in rabbits and rats) and the subchronic and chronic toxicities (in rats) of Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a potentially useful pharmaceutical excipient, were investigated. 1) In the acute toxicity study (single oral dose of 2.5 g/kg), no deaths or behavioral abnormalities were observed. Thus, LD50 is higher than 2.5 g/kg. 2) In the subchronic toxicity study (0.63, 1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 2 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in rats of both sexes, but the effect was not statistically significant. 3)In the chronic toxicity study (1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 6 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in male rats, but it was not statistically significant. 4)Various biochemical and physiological abnormalities in rats were noted in all groups (including the control groups) in the toxicity studies, but there appeared to be no significant dose-related finding attributable to the administration of HPMCAS.

Topics: Administration, Oral; Animals; Body Weight; Eating; Female; Hematologic Tests; Kidney; Lethal Dose 50; Liver; Lung; Male; Methylcellulose; Myocardium; Rabbits; Rats; Spleen; Time Factors

A fertility study was carried out in Slc: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day. Male rats were treated with HPMCAS from 60 days before pairing until the completion of mating. Female rats received HPMCAS for 22 days, from 14 days prior to mating up to Day 7 of gestation. All pregnant females were sacrificed on Day 21 of gestation and all fetuses were examined for abnormalities. No abnormal signs were seen in mating or fertility in the rat treated with HPMCAS. No external, internal and skeletal anomalies attributable to HPMCAS were observed in the fetuses. It was concluded that HPMCAS had no harmful effect on mating, fertilization, implantation, or embryonic development.

Topics: Administration, Oral; Animals; Body Weight; Bone and Bones; Drinking; Eating; Embryo Implantation; Female; Fertility; Fetus; Male; Methylcellulose; Pregnancy; Rats; Rats, Inbred Strains

A teratogenicity study was carried out in S1c: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on Day 21 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. HPMCAS caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Body Weight; Bone and Bones; Drinking; Eating; Female; Fetus; Hypromellose Derivatives; Male; Methylcellulose; Organ Size; Pregnancy; Rats; Rats, Inbred Strains; Reproduction; Weaning

A teratological study was carried out in New Zealand White rabbits in order to examine the teratogenic potentiality of HPMCAS, a useful pharmaceutical excipient. HPMCAS was orally administered at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period of 13 days from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 29 of gestation and their fetuses were examined. The administration of HPMCAS during a period of organogenesis produced no embryotoxic and teratogenic effects as well as no influence on behavior, appearance and growth of animals.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Body Weight; Bone and Bones; Drinking; Eating; Female; Fetus; Methylcellulose; Pregnancy; Rabbits

A perinatal and postnatal study was carried out in Slc: SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1,250 and 2,500 mg/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of the offsprings was observed. In the administered group of 2500 mg/kg, the liver weight was significantly increased in males and showed a tendency to increase in females as compared with control. No significant differences between the control group and the administered groups were found in postnatal growth and differentiation, behavior and reproductive ability of male and female offsprings.

Topics: Administration, Oral; Animals; Animals, Newborn; Body Weight; Bone Development; Drinking; Eating; Female; Fetus; Male; Methylcellulose; Organ Size; Pregnancy; Rats; Rats, Inbred Strains; Reproduction

Topics: Animals; Body Weight; Brain Neoplasms; Carboxymethylcellulose Sodium; Dose-Response Relationship, Drug; Interferons; Male; Methylcellulose; Neoplasm Transplantation; Nimustine; Nitrosourea Compounds; Peptides; Picibanil; Poly I-C; Polylysine; Rats

Topics: Animals; Body Weight; Carboxymethylcellulose Sodium; Cricetinae; Fasting; Glutathione; Liver; Male; Mesocricetus; Methylcellulose; Mice

Topics: Appetite; Body Weight; Feeding Behavior; Humans; Hunger; Methylcellulose; Obesity; Salivation

The effects of solid non-nutritive diet on pylorus-ligation ulcers were tested. An experimental group of 16 rats received a bulky mixture of silica and methylcellulose during 48 hr prior to ligation. Control rats were food deprived for the same period of time. A multivariate analysis of variance was applied to nine measures of the study. It was found that rumenal ulceration and total acidity were lower in experimental animals than in controls. This finding confirms a previous observation indicating that the physical property of diet has antiulcerogenic effects.

Topics: Animals; Body Weight; Diet; Dietary Fiber; Female; Gastric Juice; Ligation; Male; Methylcellulose; Pylorus; Rats; Silicon Dioxide; Stomach; Stomach Ulcer

Is there an age-related decrement in the regulation of calorie intake? The results of Experiment I indicated that there was an age-related decrement in calorie intake and body weight of rats in response to dilution of their diet with non-nutritive cellulose. Was this decrement due to an age-related increase in reactivity to the sensory and hedonic aspects of the adulterated diet? The results of Experiment II indicated that older rats maintained their calorie intake and body weight as well as younger rats in response to dilution of their diet with water but decreased their calorie intake and body weight to a greater degree than younger rats when the water-diet mixture was adulterated by quinine. The results of these experiments suggest that the regulation of calorie intake remains intact over a large segment of the life of the rat, but can be overridden by age-related increases in reactivity to the sensory and hedonic aspects of the diet.

Topics: Aging; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Diet; Energy Intake; Female; Male; Methylcellulose; Quinine; Rats; Taste

The effects of splenic artery ligation (SAL) were examined in Sprague-Dawley rats with methyl-cellulose-induced hypersplenism. When performed close to the splenic hilium, SAL effectively reduced functioning splenic mass and raised peripheral counts of leukocytes and platelets, a response similar to that following total splenectomy. In hypersplenism, therefore, a satisfactory hematologic response may not necessary require total ablation of the spleen but merely substantial reduction of functioning splenic tissue.

Topics: Animals; Blood Cell Count; Blood Platelets; Body Weight; Hematocrit; Hypersplenism; Leukocyte Count; Ligation; Male; Methylcellulose; Rats; Splenectomy; Splenic Artery

The effect of two bulk-forming appetite depressants, methylcellulose and gum guar, on food intake has been studied in 11 (4 male, 7 female) healthy volunteers--3 of whom were overweight. 10 g of active ingredient were given in two equal doses daily for periods of 1 week of each agent. Individually weighed dietary intakes were obtained over four consecutive weeks; the first and third weeks were without medication. Both gum guar and methylcellulose were equally effective in reducing appetite by 10%.

Topics: Adult; Appetite Depressants; Body Weight; Female; Galactans; Humans; Male; Mannans; Methylcellulose; Obesity; Plant Gums; Polysaccharides

Blood volume in "hypersplenic" and normal rats was assessed by a simultaneous measurement of erythrocyte and plasma volumes by means of 59Fe-labelled erythrocytes and 131I-labelled human serum albumin, respectively. The "hypersplenic" condition was induced by prolonged intraperitoneal application of methylcellulose. Mean blood volume in normal rats was 6.3 ml/100 g body weight, the venous haematocrit being 48%. Mean blood volume in "hypersplenic" rats was 7.5 ml/100 g body weight, and the venous haematocrit lower by 22% than in normal animals. Compared with normal animals, the erythrocyte volume in "hypersplenic" rats was lower by 15% only. Plasma volume in "hypersplenic" rats exceeded the compensation in response to the reduction in erythrocyte mass. In addition to haemolysis, haemodilution due to plasma expansion seemed to be responsible for the anaemia in "hypersplenic" rats.

Topics: Animals; Blood Volume; Body Weight; Erythrocytes; Hematocrit; Hypersplenism; Male; Methylcellulose; Organ Size; Rats

Topics: Administration, Oral; Age Factors; Animals; Animals, Laboratory; Biopharmaceutics; Body Temperature; Body Weight; Dose-Response Relationship, Drug; Injections, Intramuscular; Injections, Intraperitoneal; Injections, Intravenous; Lethal Dose 50; Male; Methylcellulose; Mice; Pentobarbital; Rats; Reflex; Sex Factors; Species Specificity; Time Factors; Toxicology; Viscosity; Water

Topics: Aged; Anemia; Animals; Body Weight; Chromium Radioisotopes; Disease Models, Animal; Felty Syndrome; Female; Half-Life; Hemoglobins; Humans; Hypersplenism; Injections, Intraperitoneal; Iodine Radioisotopes; Methylcellulose; Organ Size; Plasma Volume; Prednisone; Rats; Spleen

Topics: Adult; Animals; Antilymphocyte Serum; Azathioprine; Body Weight; Drug Synergism; Guanethidine; Humans; Kidney Transplantation; Liver Transplantation; Male; Methylcellulose; Mice; Nephrectomy; Neuromuscular Nondepolarizing Agents; Potassium; Toxiferine; Transplantation, Homologous; Tubocurarine

Topics: 1-Propanol; Alanine Transaminase; Alkaline Phosphatase; Animals; Blood Urea Nitrogen; Body Weight; Diet; Dogs; Erythrocyte Count; Feeding Behavior; Female; Hematocrit; Hemoglobins; Leukocyte Count; Male; Methylcellulose; Mortality; Organ Size; Rats; Urine

Topics: Alanine Transaminase; Animals; Barbiturates; Blood Proteins; Body Weight; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Enzyme Induction; Hydrocarbons, Halogenated; Intubation, Gastrointestinal; Male; Methylcellulose; Mice; Mice, Inbred Strains; Microsomes, Liver; Phenobarbital; Phosphorus; Rats; Rats, Inbred Strains; Sulfobromophthalein; Time Factors

Topics: Administration, Oral; Adolescent; Adrenal Gland Diseases; Adrenocorticotropic Hormone; Adult; Aged; Animals; Asthma; Body Weight; Child; Dyspnea; Female; Humans; Male; Methylcellulose; Middle Aged; Pituitary-Adrenal Function Tests; Prednisone; Sodium Chloride; Swine

Topics: Animals; Blood Cell Count; Blood Platelets; Body Weight; Cell Survival; Chromium Isotopes; Hemoglobinometry; Hypersplenism; Kidney; Liver; Lung; Methylcellulose; Myocardium; Organ Size; Rats; Rats, Inbred Strains; Spleen

Topics: Animals; Antibodies; Body Weight; Carbon Isotopes; Complement System Proteins; Guinea Pigs; Leukocytes; Methylcellulose; Necrosis; Norepinephrine; Opsonin Proteins; Phagocytosis; Salmonella typhimurium; Shigella; Sodium Chloride; Staphylococcus; Sympathetic Nervous System

Topics: Acetates; Aminopyrine; Analgesics; Animals; Anticonvulsants; Blood Glucose; Blood Proteins; Body Weight; Carrageenan; Cholesterol; Citrates; Female; Male; Methylcellulose; Mice; Oxyphenbutazone; Pectins; Pentobarbital; Pentylenetetrazole; Pharmacology; Phenytoin; Starvation; Time Factors; Toxicology

Topics: Adenoma; Animals; Body Weight; Carcinoma; Carcinoma, Hepatocellular; Diet; Female; Food Additives; Genital Neoplasms, Female; Liver Neoplasms; Lung Neoplasms; Male; Methylcellulose; Neoplasms; Rats; Skin Neoplasms; Urogenital Neoplasms