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Biomedical subjects

H S Sitren

Publications and source records attributed to H S Sitren.

At least 19 recordsLinked to original sources
PubMed1990

Differential role of prostaglandin E1 on tumor metastasis.

Previous studies from our laboratory have shown that intravenous (iv) infusion of pharmacologic doses of prostaglandin E1 (PGE1) inhibits "spontaneous" metastases in mice bearing Lewis Lung carcinoma (LLC). This study was done to determine the effect of iv PGE1 on "artificial" metastases. Male hybrid mice (20 g) underwent iv catheterization and were begun on continuous infusions of either PGE1 at 10 micrograms/kg/min or 0.9% NaCl (NS). After 2 days, each mouse received an iv injection of 10(5) viable LLC cells and was continued on the infusion regimens. Pulmonary metastatic nodules were enumerated and measured 12 days after injection. The iv infusion of PGE1 increased the metastatic rate 6-fold, the number of metastases greater than or equal to 2 mm in diameter 7-fold, and the number of metastases greater than or equal to 3 mm in diameter 14-fold. Thus, PGE1 demonstrates differential effects on tumor metastases, acting as a promotor of artificial metastases, in contrast to its antimetastatic effect on an intact primary tumor. When the promotional effect of iv PGE1 on artificial metastases is evaluated in light of our previous studies, it can be concluded that the inhibitory effect of PGE1 on spontaneous metastases from an intact tumor is secondary to the effect of PGE1 at the level of the primary tumor, and not in the circulation or at the target organ of metastases (lung).

Alprostadil↗
PubMed1990

Inhibition of tumor growth and metastasis by chronic intravenous infusion of prostaglandin E1.

The role of prostaglandins and their synthesis inhibitors in malignant disease is undefined. The following studies were done to determine the effects of continuous intravenous prostaglandin E1 (PGE1) or a prostaglandin synthesis inhibitor, indomethacin, on tumor growth and metastasis in mice bearing Lewis lung carcinoma. Male B6D2F1 mice underwent tumor implantation in the right axilla on day 0. After 10 days of tumor growth, mice underwent intravenous (IV) catheterization and were infused with either PGE1 at 3 micrograms/kg/minute (PG-LOW), PGE1 at 6 micrograms/kg/minute (PG-HIGH), indomethacin (INDO) at 1 microgram/kg/minute, or normal saline (NS). After 10 days of infusion, tumor volume, tumor weight, and the number of metastases greater than 2 mm in diameter were significantly decreased, and tumor doubling time was significantly prolonged in the PG-HIGH group compared to NS controls. None of the other experimental groups showed differences in these parameters. A second experiment with a similar experimental design was done infusing PGE1 at 6 micrograms/kg/minute and at 12 micrograms/kg/minute to determine the maximum dose response of IV PGE1. Again a decrease in tumor volume, tumor weight, and metastatic rates were identified when compared to saline control, but there were no significant difference between the two doses of PGE1.

Alprostadil↗
PubMed1990

Tolerance to long-term feeding of isolated peanut lectin in the rat: evidence for a trophic effect on the small intestines.

Previously we have shown that rats fed a diet containing raw peanut meal as the sole source of protein exhibited alterations in enzyme activity and composition of certain organs. To determine the effects of isolated peanut lectin on body growth and on the intestines, experiments were carried out in weanling, male, Sprague-Dawley rats fed a casein diet incorporated with purified peanut lectin at three levels, 0.004, 0.04, and 0.2% for 23 days. Body weight gain was normal with all three diets. In rats fed the 0.004 and 0.04% peanut lectin, there were no changes in any of the small intestinal mucosal parameters under study. However, in rats consuming the 0.2% peanut lectin diet, the proximal, mid, and distal third regions of the small intestines all showed marked increases in mucosal weight, protein, and DNA contents, but without altered villus morphology. Of the 3 brush border enzymes studied, namely maltase, gamma-glutamyltranspeptidase, and alkaline phosphatase, none was altered in activity in any region, suggesting that microvillus integrity was normal. These results are similar to the reported actions of red kidney bean lectin on the intestines. We conclude that peanut lectin at up to 0.2% of the diet does not inhibit food intake or growth of weanling rats and is apparently trophic for all areas of the small intestines.

Alkaline Phosphatase↗
PubMed1989

Lability of steroid hormone receptors following devascularization of breast tumors.

Ischemia may invalidate hormone-receptor analyses. This study determined the effects of progressive ischemia on steroid hormone-receptor analyses. Breast cancer was induced in 50- to 60-day-old female Holtzman rats by intragastric administration of 25 mg of 7,12-dimethylbenz[a]anthracene. After 90 days, rats were anesthetized and breast tumors were devascularized in vivo. At 0, 30, 60, 90 and 150 minutes, a biopsy specimen from each tumor was taken and rapidly frozen. Steroid binding capacity for estrogen (ER), progesterone (PR), and androgen (AR) receptors was determined by incubation with tracer receptor ligand. Ischemia decreased ER and AR levels by 30 minutes, whereas PR levels were unchanged through 150 minutes of ischemia. Following mastectomy, tylectomy, or breast biopsy, PR may be the most reliable of the hormone receptors for determining endocrine-responsive breast cancer. However, for accurate determination of all hormone receptors, specimens should be frozen in liquid nitrogen immediately, then preserved at -70 degrees C, or processed immediately.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Correlation of estrogen, progesterone, and androgen receptors in breast cancer.

Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Partial hepatectomy decreases pancreatic parenchymal enzyme activity.

In previous studies of liver regeneration following partial hepatectomy (PH) in rats, we noted a decrease in serum amylase activity. The present study was carried out to determine if the decrease in serum amylase following PH corresponds to a decrease in pancreatic parenchymal exocrine enzyme activity. Male Wistar rats (275 g) underwent either 60% PH or sham laparotomy (SL). A third group, serving as controls (CON), received no surgical procedure. All groups were pair-fed a nutritionally balanced diet. After 48 hr, pancreas, blood, and liver were removed for analysis. Results showed that PH decreased pancreatic parenchymal protein by 43%, lipase by 44%, and trypsin by 22% compared to controls. Serum amylase decreased by 28%, a finding similar to previous experiments. However, pancreatic parenchymal amylase activity was not affected. It remains to be determined whether the reduced pancreatic function affects digestion and absorption.

Amylases↗
PubMed1987

Causative factors for decreased pulmonary metastasis in parenterally fed mice.

Total parenteral nutrition (TPN) with fat and/or glucose as the caloric source is associated with a decrease in pulmonary metastasis in mice bearing subcutaneously implanted Lewis lung carcinoma. Five groups of white mice bearing Lewis lung carcinoma were assigned to receive various isocaloric and isonitrogenous oral and parenteral feedings: TPN, utilizing all nonnitrogen energy from glucose; per os, utilizing all nonnitrogen calories from glucose; electrolyte, utilizing nonnitrogen calories provided from a balanced casein diet and receiving an isovolemic infusion of electrolytes in the same composition as the TPN formula; 1/4 normal saline, also consuming the casein diet and receiving an isovolemic infusion of 1/4 normal saline; and an oral casein control (CON) without infusion. Results showed that there were no significant differences in tumor volume changes or tumor doubling time among the groups. However, tumor weight was significantly lower in groups receiving the TPN solution either orally or parenterally in comparison to the oral casein control. Pulmonary metastases were significantly lower in all parenteral groups, irrespective of solution composition, compared to the CON group. Thus it appears that parenteral fluid load rather than composition of the solution is the causative factor for the decrease in pulmonary metastases.

Administration, Oral↗
PubMed1987

Decreased lung metastasis and tumor growth in parenterally fed mice.

The influence of alternate forms of nutritional support on primary tumor growth rate, tumor DNA synthesis rate, and number of lung metastases was examined in Swiss mice bearing subcutaneously implanted Lewis lung carcinoma (LLC). From Day 14 through 22 postimplant, mice were fed by continuous intravenous infusion of dextrose/amino acid (TPN), were offered the same solution from a feeding bottle (PO), were offered a casein-based, solid diet (CASEIN), or were infused with an electrolyte (ELECT) solution while energy and nitrogen were provided from the casein diet. Tumor weight and doubling time were decreased in the PO group compared to CASEIN; however, host weight decreased by 22% in the PO group. Tumor weight and DNA synthesis were decreased in the TPN group compared to CASEIN, and host weight increased by 4.6%. The decreased rate of tumor growth in the PO group was not reflected in a decrease in DNA synthesis, perhaps a result of the circadian pattern of DNA synthesis as previously reported for LLC. The number of metastatic lung nodules was significantly decreased in both the TPN and ELECT groups compared to PO and CASEIN, suggesting that intravenous fluid load rather than nutrient intake was the causative factor. In this host-tumor system, parenteral feeding was associated with a decrease in primary tumor weight and DNA synthesis rate, maintenance of host weight, and a decrease in pulmonary metastatic disease compared to mice fed a conventional diet.

Animals↗
PubMed1987

Dosage form and formulation effects on the bioavailability of vitamin E, riboflavin, and vitamin B-6 from multivitamin preparations.

The effects of formulation factors and pharmaceutical dosage form on the bioavailability of RRR-alpha-tocopherol (d-alpha-tocopherol), riboflavin, and pyridoxine hydrochloride were studied after administration of two capsule formulations and a tablet to 12 normal humans. Absorption of RRR-alpha-tocopherol was increased from the Aquabiosorb soft elastic gelatin (SEG) capsule formulation compared with the modified standard-SEG capsule and the commercial tablet. There were no significant differences in bioavailability of riboflavin and pyridoxine hydrochloride between the SEG formulation and the tablet albeit a trend toward consistent absorption was seen from the SEG formulation. The modified-SEG formulation exhibited significantly lower bioavailability for these water-soluble vitamins. The enhanced bioavailability of vitamin E and the trend towards faster and more consistent absorption of riboflavin and vitamin B-6 from the SEG formulation may be related to the surfactant vehicle employed and the attendant wetting properties. The results also suggest ethnic differences in vitamin bioavailability.

Adult↗
PubMed1987

Comparison of glucose and glucose plus lipid as caloric sources in parenterally fed rats.

This study investigated the etiology of fat infiltration of the liver during total parenteral nutrition. We measured the content of liver lipids, serum lipids, liver lipogenic enzymes, rates of in vivo fatty acid synthesis, and carcass composition in rats during continuous intravenous (iv) and intragastric (ig) feeding of two diets containing either 100% glucose or 75% glucose-25% lipid (20% Intralipid). Two groups of orally (O) fed rats were given solid diets similar to either the glucose or glucose-lipid solution in energy and nitrogen content. All six groups of rats (285-295 g) received 230 kcal X kg-1 X day -1 and 766 mg N X kg-1 X day-1. Total liver fat was greater after feeding the glucose diet ig rather than iv. However, feeding the glucose-lipid diet ig but not iv reduced the accumulation of liver fat by 49%. There were no differences in serum glucose concentrations among the three groups fed the glucose solution. Serum glucose concentrations in iv and O rats fed either diet were not significantly different; whereas feeding the glucose-lipid solution ig lowered serum glucose compared with the 100% glucose solution. Insulin concentrations were similar among all groups. The concentrations of serum triglycerides and cholesterol were higher in the groups fed the glucose-lipid diet. The activities of the liver lipogenic enzymes and rates of fatty acid synthesis were higher in iv- and ig-fed rats receiving the glucose diet compared with the glucose-lipid diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Bacterial endotoxin retention by inline intravenous filters.

Filters used in i.v. administration sets were tested for their ability to retain bacterial endotoxins for up to 96 hours of continuous infusion. Inline filters composed of cellulose ester, polyacrylate, polypropylene, polyethylene, or Posidyne Nylon 66 were used during continuous infusion of 5% dextrose injection at 83 mL/hr. One milliliter of inoculum containing 10(8) Escherichia coli was injected through a port upstream from the filter. A bacterial filter was used to monitor the sterility of effluent from the inline filters. The effluent was tested with limulus amebocyte lysate (LAL) that could detect endotoxin concentrations greater than 50 pg/mL. A control solution was monitored for viability of the bacteria throughout the course of the study, and positive endotoxin controls were used to confirm the sensitivity of the LAL. Samples of effluent were tested at 0, 4, 19, 24, 48, 72, and 96 hours. Effluent from all filters was sterile throughout the study. LAL assay indicated that only the effluent from filters containing Posidyne Nylon 66 was free of endotoxins for 96 hours. Effluent from the other filters contained endotoxins immediately after injection of the E. coli. Of the inline filters tested, only the one composed of Posidyne Nylon 66 was able to retain E. coli endotoxin for 96 hours. Further study is needed with E. coli and other microorganisms that are likely contaminants of i.v. infusions.

Drug Contamination↗
PubMed1985

The effect of energy substrate manipulation on tumor growth and metastasis and intermediary metabolism in the parenterally fed mouse.

The effect of N-free energy substrate manipulation on tumor growth and metastasis, host maintenance, and intermediary metabolism was studied in parenterally fed Swiss mice bearing subcutaneously implanted Lewis lung carcinoma. Non-N energy was provided from dextrose (CHO), lipid emulsion (FAT), or a 75:25 balanced (BAL) solution, infused from day 14 through day 22 postimplant. Control mice were offered equivalent energy and N from a balanced, casein-based solid diet (CAS). Tumor-doubling time was significantly prolonged in the CHO group compared to FAT and CAS. Pulmonary metastatic nodules were decreased in number in all parenterally fed mice compared to CAS, suggesting that the route of administration altered pulmonary physiology in such a way that the transmissability and/or growth of the tumor cells was inhibited. Tumor-free body weight was maintained in the CHO (+ 1.3%) and BAL (+ 0.3%) groups. However, significant weight loss occurred, despite equal intake, in the FAT (-4.7%) and CAS (-7.5%) groups. The energy appeared to be channeled into nonoxidative pathways, reflected by an increase in hepatic and adipose tissue lipogenesis and hepatic glycogen content. During the period studied, parenteral dextrose/amino acid infusion in this host-tumor system resulted in a decrease in primary tumor growth and optimal host maintenance compared to fat-based TPN and enteral feeding of a balanced, solid diet. Tumor metastasis was decreased in all parenterally fed mice, a phenomenon related to the route of administration and apparently independent of energy substrate.

Adipose Tissue↗
PubMed1980

Circadian rhythmicity in several small intestinal functions is independent of use of the intestine.

Fifty milliliters of a liquid diet were administered daily to rats in three different ways: 1) orally, beginning at 0000 h; 2) by continuous intravenous infusion; and 3) by discontinuous intravenous infusion from 0000 to 1400 h. Animals were killed every 6 h over a 24-h period. Activity profiles as a function of time of day were determined for the following small intestinal parameters; monosaccharide transport; five disaccharidases; alkaline phosphatase; gamma-glutamyltransferase; leucylnaphthylamide hydrolyzing activity; villus height and width; and number of columnar cells lining a villus section. Circadian rhythmicity as previously reported was observed for all parameters in rats fed orally for 7 days but was not observed in any parameters in rats fed by continuous infusion for 9 days. Rats fed by discontinuous infusion for 10 days maintained circadian rhythmicity in the following functions: monosaccharide transport; disaccharidase activities; and columnar cell number. Thus, rhythmicity in these functions can exist without nutrient delivery to the alimentary tract and presumably arises from involvement of a neuro-endocrine component. The other activities tested appear to require the alimentary tract for the existence of circadian rhythmicity.

Administration, Oral↗
PubMed1979

Regional variability in circadian rhythmicity of intestinal digestive-absorptive functions.

The circadian rhythms of sucrase, maltase, isomaltase, trehalase, lactase, gamma-glutamyltransferase, leucylnaphthylamide hydrolyzing activity, alkaline phosphatase and monosaccharide transport were assessed in each fifth of the small intestine of the rat in order to determine if an entire enzyme or transport system population responded in a similar manner or if there were regional differences. Animals were maintained under a light-dark cycle and fed from 1400-1800, EST for 7 days. Functional activities were assessed every 4 h for 24 h, inclusively. Quantitative, and in a few instances, qualitative differences in different areas of the intestine were found for all functions. There were portions of the lactase and alkaline phosphatase populations which displayed no rhythmicity in activity. When rhythmicity was observed there were differences in the activity patterns along the intestine for all functions. Thus, the rhythm patterns obtained from homogenates of the entire small intestine are a composite of the patterns in regions of high average activity. Also, there appears to be a reasonable amount of local control of the various functions.

Alkaline Phosphatase↗
PubMed1978

The effects of meal-feeding at different times of the day on daily changes in serum insulin, gastrin and liver enzymes in the rat.

Restricted feeding at two distinct times of the day was associated with different adaptive responses in rats. Animals meal-fed from 1400 to 1800 hours for 6 days demonstrated feeding-cued circadian rhythms in liver weight and in liver transaminase and lactic dehydrogenase enzyme activities. Daily fluctuations in the levels of blood immunoreactive insulin and gastrin were also found to be cued by food intake. By comparison, rats fed from 0700 to 1100 hours for 6 days exhibited altered liver function and blood immunoreactive gastrin patterns. It is suggested that meal-feeding in rats is associated with certain adaptive responses which are dependent upon the timing of the meal. The observed metabolic alterations consequent to meal-feeding are much more apparent in morning-fed than in afternoon-fed animals.

Adaptation, Physiological↗
PubMed1977

Nitrogen retention in rats fed on diets enriched with arginine and glycine. 1. Improved N retention after trauma.

1. Nitrogen retention was measured in adult rats (250-350 g) subjected to the trauma of hind-leg fracture and given diets with or without arginine plus glycine supplementation. Observations were also recorded on excretion of creatine, creatinine, allantoin, and orotic acid. Liver and skeletal muscle transaminase activities were also determined. 2. When traumatized rats weighing approximately 250 g were given a diet with 200 g casein/kg, supplemented with 20 g arginine and 10 g glycine/kg (EC diet) or a casein diet made isonitrogenous with the EC diet by addition of aspartic acid (C diet), a 60-70% increase in N retention was observed for the first 5 d post-injury for animals consuming the EC diet. A soya-bean (S) diet, isonitrogenous to the diet containing 20% casein, supplemented with arginine and glycine was as effective as the EC diet in promoting significantly better N retention of traumatized rats (350 g) in comparison to rats given the C diet. 3. When the dietary casein content was reduced to 100 g/kg, supplements of 10 g arginine and 5 g glycine or 20 g arginine and 10 g glycine/kg did not improve N retention. It is suggested that both protein quality and protein quantity are important following injury. 4. An increased excretion of creatine was observed in traumatized rats given the high-protein diets supplemented with arginine and glycine. No consistent changes were noted for urine creatinine. 5. 5. Urine allantoin levels remained stable after leg-fracture in rats consuming either the C or EC diets. Differences in the levels of urine orotic acid were found during both the pre- and post-injury periods in rats given the C, EC or S diets. 6. The mechanisms responsible for the improved N retention of traumatized rats consuming the high-protein diets with supplements of arginine and glycine may be related to the role of arginine both as a constituent of muscle tissue and as an intermediate in the urea cycle. 7. In traumatized rats fed the C or EC diets, liver transaminase activity increased whereas the transaminase activity in skeletal muscle decreased. These results support the recent concept that the increased excretion of N following injury arises from diminished reutilization of amino acids by muscle tissue without an acute increase in the rate of muscle catabolism.

Alanine Transaminase↗