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Biomedical subjects

M J Fettman

Publications and source records attributed to M J Fettman.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin.

OBJECTIVE: To determine the effectiveness and safety of asparaginase administered s.c. versus i.m. for treatment of multicentric lymphoma in dogs receiving doxorubicin. DESIGN: Prospective study. ANIMALS: 49 dogs with multicentric lymphoma. PROCEDURE: Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, s.c. or i.m. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered s.c. in 23 dogs and i.m. in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses. RESULTS: Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between s.c. and i.m. groups. For dogs in clinical stage IV, i.m. administration of asparaginase significantly decreased the number of days to complete remission, compared with s.c. administration (8 vs 17 days, respectively). For dogs in clinical stage III, i.m. administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated i.m. had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated s.c. Asparaginase toxicoses were not observed regardless of the route of administration. CLINICAL IMPLICATIONS: For dogs with multicentric lymphoma that are receiving doxorubicin, i.m. treatment with asparaginase is more effective than s.c. treatment.

Animals↗
PubMed1999

Effects of dietary cysteine on blood sulfur amino acid, glutathione, and malondialdehyde concentrations in cats.

OBJECTIVE: To determine effects of dietary cysteine on blood sulfur amino acids (SAA), reduced glutathione (GSH), oxidized glutathione (GSSG), and malondialdehyde (MDA) concentrations in cats. ANIMALS: 12 healthy adult cats. PROCEDURE: Cats were fed diets with a nominal (0.50 g/100 g dry matter [DM]), moderate (1.00 g/100 g DM), or high (1.50 g/100 g DM) cysteine content in a 3 X 3 Latin square design with blocks of 8 weeks' duration. Venous blood samples were collected after each diet had been fed for 4 and 8 weeks, and a CBC and serum biochemical analyses were performed; poikilocyte, reticulocyte, and Heinz body counts were determined; and MDA, GSH, GSSG, and SAA concentrations were measured. RESULTS: Blood cysteine and MDA concentrations were not significantly affected by dietary cysteine content. Blood methionine, homocysteine, and GSSG concentrations were significantly increased when cats consumed the high cysteine content diet but not when they consumed the moderate cysteine content diet, compared with concentrations obtained when cats consumed the nominal cysteine content diet. Blood GSH concentrations were significantly increased when cats consumed the moderate or high cysteine content diet. CONCLUSIONS: Increased dietary cysteine content promotes higher blood methionine, homocysteine, GSH, and GSSG concentrations in healthy cats. CLINICAL RELEVANCE: Supplemental dietary cysteine may be indicated to promote glutathione synthesis and ameliorate adverse effects of oxidative damage induced by disease or drugs.

Amino Acids↗
PubMed1998

Duration of effects of dietary fish oil supplementation on serum eicosapentaenoic acid and docosahexaenoic acid concentrations in dogs.

OBJECTIVE: To determine how long serum concentrations of omega-3 fatty acids remain elevated after cessation of dietary fish oil supplementation. ANIMALS: 12 healthy Beagles. PROCEDURE: Baseline serum concentrations of linoleic acid, linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were measured. Dogs were then fed a diet supplemented with soybean oil or fish oil for 8 weeks, and serum fatty acid concentrations were measured while dogs were fed the experimental diets and for 18 weeks after they were switched to a maintenance diet. RESULTS: For dogs fed the fish oil diet, serum EPA and DHA concentrations were significantly increased by week 1 and remained increased for 7 (DHA concentration) or 3 (EPA concentration) weeks after dietary fish oil supplementation was discontinued. CONCLUSIONS: In dogs, supplementation of the diet with fish oil may have effects for several weeks after dietary supplementation is discontinued. CLINICAL RELEVANCE: Studies of the effects of fish oil supplementation that use a crossover design should allow for an appropriate washout period.

Animals↗
PubMed1997

Alterations in carbohydrate metabolism in dogs with nonhematopoietic malignancies.

OBJECTIVE: To determine whether alterations in carbohydrate metabolism exist in dogs with nonhematopoietic malignancies but without evidence of weight loss or cachexia. ANIMALS: 90 dogs with nonhematopoietic malignancies and 18 control dogs. PROCEDURE: An intravenous glucose tolerance test was done in 90 dogs with previously untreated nonhematopoietic malignancies and in 18 clinically normal dogs. These dogs also had no evidence of unrelated diseases that would affect glucose metabolism. None of the dogs had evidence of cachexia. Samples were assayed for glucose, lactate, and insulin concentrations. This procedure was repeated for 45 of the tumor-bearing dogs from which all gross evidence of tumor was completely excised and evidence of diseases that would alter carbohydrate metabolism did not exist. RESULTS: The mean of all time points during the intravenous glucose tolerance test (ie, 0, 5, 15, 30, 45, and 60 minutes) for lactate (12.9 +/- 6.7 mg/dl) and insulin (69.1 +/- 44.9 microU/ml) concentrations in untreated dogs with nonhematopoietic malignancies were significantly higher than values for controls (lactate, 9.7 +/- 4.3 mg/dl; and insulin, 31.7 +/- 11.5 microU/ml). This increase in lactate and insulin values did not return to normal when the dogs were rendered free of all observable evidence of cancer after surgery. CONCLUSIONS: Carbohydrate metabolism is altered in dogs with a variety of nonhematopoietic malignancies and these abnormalities do not abate when dogs are rendered free of gross evidence of malignant disease after surgery. CLINICAL RELEVANCE: Alterations in carbohydrate metabolism may result in decreased quality of life and may be associated with the paraneoplastic syndrome, cancer cachexia.

Animals↗
PubMed1996

Effects of dietary n-3 fatty acid supplementation versus thromboxane synthetase inhibition on gentamicin-induced nephrotoxicosis in healthy male dogs.

OBJECTIVE: To evaluate the protective effects of dietary n-3 fatty acid supplementation versus treatment with a thromboxane synthetase inhibitor (TXSI) in dogs given high-dose gentamicin. DESIGN: Clinicopathologic and renal histopathologic changes induced by gentamicin (10 mg/kg of body weight, IM, q 8 h, for 8 days) were compared in dogs fed an n-3 fatty acid-supplemented diet containing a fatty acid ratio of 5.7:1 (n-6:n-3), dogs treated with CGS 12970 (a specific TXSI given at 30 mg/kg, PO, q 8 h, beginning 2 days prior to gentamicin administration), and control dogs. The TXSI-treated and control dogs were fed a diet with a fatty acid ratio of 51.5:1 (n-6:n-3). Both diets were fed beginning 42 days prior to and during the 8-day course of gentamicin administration. ANIMALS: Eighteen 6-month-old male Beagles, 6 in each group. RESULTS: After 8 days of gentamicin administration, differences existed among groups. Compared with n-3-supplemented and control dogs. TXSI-treated dogs had higher creatinine clearance. Both TXSI-treated and n-3-supplemented dogs had higher urinary prostaglandin E2 and E3 (PGE2/3) and 6-keto prostaglandin F1a (PGF1a) excretion, compared with control dogs. Urinary thromboxane B2 (TXB2) excretion was higher in n-3-supplemented and control dogs, compared with TXSI-treated dogs. Urine PGE2/3-to-TXB2 and PGF(in)-to-TXB2, ratios were increased in TXSI-treated dogs, compared with n-3-supplemented and control dogs, and these ratios were increased in n-3-supplemented dogs, compared with control dogs. In addition, TXSI-treated and n-3-supplemented dogs had lower urinary protein excretion, compared with control dogs. Proximal tubular necrosis was less severe in TXSI-treated dogs, compared with control dogs. CONCLUSION: Treatment with CGS 12970 prior to and during gentamicin administration prevented increases in urinary TXB2 excretion and reduced nephrotoxicosis. CLINICAL RELEVANCE: Increased renal production/excretion of thromboxane is important in the pathogenesis of gentamicin-induced nephrotoxicosis.

Animals↗
PubMed1996

Single intravenous and multiple dose pharmacokinetics of gentamicin in healthy llamas.

OBJECTIVE: To determine the pharmacokinetics of gentamicin sulfate in healthy llamas after i.v. administration of a single bolus and after repeated parenteral administration. DESIGN: Prospective clinical trial. ANIMALS: 19 clinically normal, adult male llamas for the single-dose trial and 10 of the 19 llamas for the multiple-dose trial. PROCEDURE: In the first trial, llamas were given gentamicin (5 mg/kg of body weight, i.v.) as a single bolus, and serum gentamicin concentration was monitored over the next 48 hours. 2 months later, llamas were given gentamicin (2.5 mg/kg) i.v. for the first day, then IM every 8 hours for 7 days. Serum gentamicin concentration and indices of renal function and damage were monitored during the 7 days. RESULTS: There were no significant dose- or time-related differences in clearance of the drug; volume of distribution; apparent coefficients of the distribution and elimination phases, alpha and beta, respectively; mean residence time; or distribution (t1/2 alpha) and elimination phase (t1/2 beta) half-lives. The 5 mg/kg i.v. kinetic study revealed t1/2 alpha of 14.5 +/- 5.06 minutes and t1/2 beta of 166 +/- 20.5 minutes. The 2.5 mg/kg i.v. kinetic study revealed t1/2 alpha of 17.7 +/- 6.59 minutes and t1/2 beta of 165 +/- 40.3 minutes. Peak serum gentamicin concentration averaged 10.10 micrograms/ml in the multiple-dose trial, and trough concentration averaged 1.50 micrograms/ml. CONCLUSIONS: Dose effects were not observed for gentamicin clearance, volume of distribution, or half-lives. Multiple dosing at 2.5 mg/kg every 8 hours does not appear to cause renal impairment in healthy llamas. CLINICAL RELEVANCE: Gentamicin pharmacokinetic variables in llamas appear to resemble those in other ruminant species.

Animals↗
PubMed1996

Effect of anesthesia and surgery on energy expenditure determined by indirect calorimetry in dogs with malignant and nonmalignant conditions.

OBJECTIVE: To determine energy expenditure (EE) of apparently resting, client-owned dogs with malignant or nonmalignant diseases that were recovering from anesthesia and surgery, and compare those values with values from clinically normal, apparently resting, client owned dogs. ANIMALS: 40 apparently resting, client-owned dogs that had been given general anesthesia for various elective and nonelective surgical procedures, and 30 apparently resting, clinically normal client-owned dogs used as controls. PROCEDURE: EE was determined, using an open-flow indirect calorimetry system. Each dog was evaluated before and after surgery (0, 1, 2, and 3 days after surgery, then at suture removal > 14 days later) and compared with apparently resting, clinically normal, client-owned dogs (n = 30). Parameters evaluated were rate of oxygen consumption (Vo2/kg of body weight: ml/min/kg; Vo2/kg0.75: ml/min/kg0.75), EE (EE/kg: kcal/kg/d; EE/kg0.75: kcal/kg0.75/d), and respiratory quotient. RESULTS: Surgery and anesthesia did not significantly alter any of these parameters at any time assessed in any group. The pretreatment Vo2 and EE were significantly lower in the dogs with cancer, compared with dogs of other groups. CONCLUSIONS: These data suggest that the EE of a restricted group of dogs that undergo anesthesia and surgery for malignant and nonmalignant conditions does not increase from baseline values or when compared with values in clinically normal, client-owned dogs. CLINICAL RELEVANCE: This information may be of value when planning nutritional treatment for dogs recovering from anesthesia and surgery.

Anesthesia, General↗
PubMed1996

Resting energy expenditure in dogs with nonhematopoietic malignancies before and after excision of tumors.

OBJECTIVE: To determine whether apparently resting dogs with nonhematopoietic malignancies have increased resting energy expenditure (REE), compared with clinically normal dogs. ANIMALS: 46 client-owned dogs with nonhematopoietic malignancies and 30 client-owned dogs that were clinically normal. PROCEDURE: Apparently resting, client-owned dogs with nonhematopoietic malignancies before (n = 46) and 4 to 6 weeks after (n = 30) surgical removal of tumors were compared with apparently resting, clinically normal, client owned dogs (n = 30). An open flow indirect calorimetry system was used to determine the following: rate of oxygen consumption (ml/min/kg of body weight); rate of carbon dioxide production (mls/min/kg), REE (kcal/kg/d) and respiratory quotient. Because of the wide range of body weight, REE and oxygen consumption were also expressed per kg of body weight 0.75. RESULTS: Surgical removal of the tumor did not significantly alter any of the variables measured when all dogs with tumors were assessed as a single group, or when the dogs were divided on the basis of having the following types of tumors: carcinomas and sarcomas, osteosarcomas, and mammary adenocarcinomas. None of the data obtained prior to surgical treatment from any of the dogs grouped by tumor type were significantly different from clinically normal dogs. CONCLUSIONS: REE (54.4 +/- 16 kcal/kg/d or 125 +/- 19 kcal/kg0.75/d) and, presumably, caloric requirements of dogs with nonhematopoietic malignancies are not significantly different from those obtained from clinically normal dogs (53.9 +/- 16 kcal/kg/d or 116 +/- 32 kcal/kg0.75/d). Furthermore, these variables do not change significantly when the tumor is excised and the dog is reassessed after 4 to 6 weeks. CLINICAL RELEVANCE: Knowledge that REE in dogs with solid tumors is not significantly different from REE of clinically normal dogs may be of value when planning nutritional treatment for dogs with nonhematopoietic malignancies.

Adenocarcinoma↗
PubMed1994

Practical and clinical nutritional concerns during spaceflight.

Experience with space exploration to date has raised more questions regarding nutritional requirements for astronauts than it has answered. As mission lengths continue to increase, nutrient imbalances due to alterations in intake, dietary requirements, bioavailability, or excretion, may become more important. Factors adversely affecting intake include those as straightforward as stress and as complex as space-adaptation syndrome. Metabolic alterations induced by shifts in fluid and electrolyte balance, neuroendocrine function, and changes in hepatic protein synthesis and skeletal muscle type that result in nutrient partitioning to different biochemical pathways may also affect dietary requirements. Food processing effects on nutrient stability and digestibility, which apply to limited quantities of our usual diet on Earth, may become more important for diets that contain little fresh food during extended-length missions. Whereas nutrient and water recycling through ecosystems is taken for granted on Earth, specific effects of trace contaminant accumulation will require greater attention for prolonged space flights. Human factors, esthetics, and user-friendly operations will be necessary to facilitate the psychological as well as physiological health of the astronauts.

Adaptation, Physiological↗
PubMed1994

Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs.

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.

Animals↗
PubMed1994

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1993

Energy expenditure in dogs with lymphoma fed two specialized diets.

BACKGROUND: Cancer-caused cachexia has been reported to be caused in part by an increase in energy expenditure, and diets with nutrient profiles containing 30-50% nonprotein calories as fat instead of carbohydrate may exacerbate this state of inefficient energy utilization. METHODS: Indirect calorimetry was performed on 22 dogs with high-grade lymphoblastic lymphoma that were randomized into a blind study and fed isocaloric amounts of a high-fat diet (Diet A) or a high-carbohydrate diet (Diet B) before and after remission was attained with up to five doses of doxorubicin chemotherapy (30 mg/m2 intravenously). Indirect calorimetry was also performed on 30 normal dogs for comparison. RESULTS: During the initial evaluation period, the resting energy expenditure (REE/kg0.75, P < 0.05) and respiratory quotient (RQ, P < 0.05) were significantly lower than in the controls. Six weeks after the start of the study, the REE/kg0.75 and oxygen consumption (VO2/kg0.75) were significantly (P < 0.05) lower in both groups of dogs with lymphoma compared with the controls. The RQ determined 6 weeks after the start of the study for the dogs fed Diet A was significantly (P < 0.05) lower compared with that in the controls evaluated at the same time. When the two groups of dogs with lymphoma were compared with each other, there was no significant difference in any of the outcomes. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group fed Diet A after the third evaluation period compared with the second evaluation. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group given Diet B at the fourth evaluation period compared with the fifth. CONCLUSIONS: These data suggest that energy expenditure of dogs with lymphoma decreases transiently in response to chemotherapy and remission, but these values are less than those determined in normal dogs and not altered significantly by diet.

Animals↗
PubMed1993

Repeatability of energy expenditure measurements in clinically normal dogs by use of indirect calorimetry.

Energy expenditure (EE) was determined, using an open-flow indirect calorimetry system in a group of 20 clinically normal, apparently resting, client-owned dogs. Five evaluations were performed over an 8-hour period to determine reliability of the method. The intraclass correlation coefficient was calculated as the ratio of within- and between-subject variances, using repeated-measures ANOVA. When only the middle 3 evaluations were included, the intraclass correlation coefficient was 0.87, indicating good reliability. The first evaluation was higher than the subsequent 4 evaluations for rate of O2 consumption (Vo2/kg and Vo2/kg0.75; (P < or = 0.01), and EE/kg and EE/kg0.75 (P < or = 0.005). The respiratory quotients at the first (P = 0.004) and second (P = 0.013) evaluations were different from the respiratory quotient at the fourth evaluation. Therefore, the first evaluation may not be representative of the actual EE. The mean value of at least 3 subsequent evaluations after an adequate adaptation period (5 to 10 minutes) to the equipment will be useful for predicting energy requirements of apparently resting, clinically normal dogs.

Animals↗
PubMed1992

Effects of chemotherapy and remission on carbohydrate metabolism in dogs with lymphoma.

After a 12-hour fast, blood samples were obtained from 27 dogs with previously untreated lymphoma before and 5, 15, 30, 45, and 60 minutes after an intravenous (IV) challenge with 500 mg/kg dextrose. This procedure was done for each dog before up to five treatments with the IV doxorubicin (30 mg/m2 every 3 weeks). All dogs achieved a complete remission. Samples were assayed for glucose, lactate, and insulin concentrations, and results were compared statistically with those from 16 normal control dogs of similar weight and age undergoing an identical dextrose challenge before and 3 weeks after receiving one dose of IV doxorubicin (30 mg/m2). Glucose, lactate, and insulin concentrations did not change significantly in response to glucose challenge in control dogs after doxorubicin chemotherapy. Lactate and insulin concentrations in untreated dogs with lymphoma were significantly higher than controls. This hyperlactatemia and hyperinsulinemia did not improve when dogs with lymphoma were put into remission with doxorubicin chemotherapy. The results indicate that carbohydrate metabolism is altered in dogs with lymphoma, and that these abnormalities do not improve when a complete remission is obtained with doxorubicin chemotherapy.

Animals↗
PubMed1992

Glucose metabolism in proliferating epithelial cells from the rat colon.

1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the tricarboxylic acid cycle (TCA) in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]glucose and [6-14C]glucose, respectively. 2. Refeeding after a fast induced a 2-3-fold increase in glucose flux through the OPP and TCA cycle and the degree of change was similar in colonocytes from the proximal and distal colon. 3. Butyrate at a concentration of 40 mM inhibited the OPP by 20-30% (P less than 0.05) but had no effect on the activity of the TCA cycle. Glutamine at a concentration of 2 mM decreased the glucose flux through both the OPP and the TCA cycle by 30-50% (P less than 0.05). 4. Production of 14CO2 from the oxidation of butyrate or glucose indicated that the former was 5-7 times more active in colonocytes from fasted rats. After refeeding, however, butyrate utilization was similar to fasting values in the proximal colon but significantly lower (P less than 0.05) in the distal colon.

Animals↗
PubMed1992

Hematologic features of iron deficiency anemia in llamas.

Iron deficiency anemia was identified and characterized in three 14 to 29-month-old male llamas (llama Nos. 1-3) from separate herds in Colorado. The identification of iron deficiency anemia was based on hypoferremia (serum iron = 20-60 micrograms/dl), erythrocytic features, and hematologic response to iron therapy. The anemia was moderate and nonregenerative and characterized by erythrocyte hypochromia, microcytosis (mean cell volume = 15-18 fl), and decreased mean corpuscular hemoglobin concentration (36.0-41.0 g/dl). Morphologic features unique to llamas with iron deficiency anemia included irregular distribution of hypochromia within erythrocytes and increased folded cells and dacryocytes. The cause of iron deficiency was not determined. The llamas were treated with various doses and schedules of parenteral iron dextran. Two of the llamas were monitored for up to 14 months after the start of iron therapy and experienced increases in hematocrit and mean cell volume values. In one llama, progressive replacement of microcytic cells with normal cells was visualized on sequential erythrocyte volume distribution histograms following iron therapy.

Anemia, Hypochromic↗
PubMed1992

Regional factors affecting proliferation in the large intestine of the rat.

Colonic neoplasia is more frequent in the distal colon than in the proximal colon in spontaneous human disease and in carcinogen-induced tumors in rodents. The possibility that this may reflect regional differences in morphology and in proliferative responses to fasting and refeeding was explored in this study in rats. Scanning electron microscopy revealed that the density of colonic crypts was 36% higher in the distal than in the proximal colon, while light microscopy revealed that distal crypts had 70% more colonocytes than proximal crypts. Thus, the number of colonocytes per unit area in the distal colon is approximately twice that in the proximal colon. Proliferation was assessed by the uptake of bromodeoxyuridine in vivo and showed that regions of the distal colon had greater suppression of proliferation during fasting than the cecum, and greater enhancement of proliferation during refeeding than that observed in the cecum or the proximal colon. Changes in proliferation associated with fasting and refeeding were accompanied by changes in the concentrations of short chain fatty acids, but the data did not support the hypothesis of a direct relationship between increasing concentrations of short chain fatty acids and enhanced proliferation. Regional differences in morphology and proliferation could be relevant to the greater susceptibility of the distal colon to neoplasia.

Animals↗