Growth Inhibition of Kirkman-Robbins Hepatoma by l-(l,3-Dihydroxy-2-propoxymethyl)-5,6-tetramethyIeneuraciI and Possible Mechanism of its Biological Activity

1989 ◽  
Vol 44 (11-12) ◽  
pp. 985-991 ◽  
Author(s):  
Janusz Greger ◽  
Marcin Dramiriski
Keyword(s):  
Body Weight ◽  
Biological Activity ◽  
Tumour Cell ◽  
Syrian Hamster ◽  
Tumour Growth ◽  
Nuclear Fraction ◽  
Dntp Pool ◽  
Cell Enzyme ◽  
Induced Changes ◽  
Tumour Weight

Abstract Hepatoma, Acyclonucleoside Metabolism , dN and dTMP Kinases. dNTP Pool l-(l,3-D ihydroxy-2-propoxym ethyl)-5,6-tetram ethylene-uracil (DHPTU) is a newly synthe­ sized acyclonucleoside which shows cytostatic properties. It was tested in Syrian hamster 6 days after heterotransplantation of Kirkm an-Robbins hepatoma. A reduction of tumour weight by 61% was found 48 h after its intraperitoneal (i.p .) administration in doses of 20 mg per kg of body weight. Inhibition of tumour growth is accompanied by a reduction of dThd, dGuo and dTMP kinase activities in tumourcytosol (by 91% and 74% and 55% , respectively) and decrease in contents of dTTP, dGTP and dA TP (by 92% , 77% and 67% , respectively) in dNTP pool. DHPTU is not phosphorylated by any tumour dN kinases, but undergoes cleavage with TU release in reaction catalyzed by the tumour cell enzyme, com petitively inhibited by FA . After [14C]DHPTU or [14C]TU had been given i.p. to the animals with the tumour, 90% of the subcellu­lar fraction labelling fell into the nuclear fraction. How ever, if [l4C ]DHPTU was administered with FA and DCF, 27% of radioisotope was found in the nuclear fractions and 68% in cytosol. Since D C F which prevented FA deamination to FB (which is not an inhibitor of the mentioned enzyme) reduces DHPTU-induced changes in activity of dN kinases and dTMP kinase in hepato­ ma cells, the cytostatic activity of DHPTU seems to be connected to an enzyme which releases TU from DHPTU .

scholarly journals Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 464 ◽  
Author(s):  
Bright Asare-Bediako ◽  
Sunil Noothi ◽  
Sergio Li Calzi ◽  
Baskaran Athmanathan ◽  
Cristiano Vieira ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Fundus Photography ◽  
Vascular Density ◽  
Sensitivity Index ◽  
High Fat ◽  
Permeability Studies ◽  
Induced Changes ◽  
Acellular Capillaries

We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes.

scholarly journals Clinical and in Vivo Response Following Surgery or Surgery Plus Adjuvant Chemotherapy or Immunotherapy for Colorectal Carcinoma in a Rat Model

1983 ◽  
Vol 76 (10) ◽  
pp. 833-840 ◽  
Author(s):  
A K House ◽  
M A L Maley
Keyword(s):  
Body Weight ◽  
Adjuvant Chemotherapy ◽  
Surgical Excision ◽  
The Body ◽  
Recurrent Tumour ◽  
Mesenteric Node ◽  
And Control ◽  
Tumour Weight

Two cohorts of rats, 240 with colon cancer and 150 controls, were assessed clinically and immunologically for their response to tumour and its management which was either by surgical excision alone or by surgical excision combined with either adjuvant chemotherapy or immunotherapy. The histology and invasion characteristics were observed for similarity with those of human lesions. Metastases were found in liver, lymph nodes, the peritoneum or lungs in 27% of animals during follow up. Significantly fewer adjuvant-treated rats had metastases than those receiving surgery alone ( P < 0.05), and less total tumour weight was found in the adjuvant-treated rats at four ( P < 0.03) and six ( P < 0.001) weeks postoperatively. Animals in the adjuvant immunotherapy group survived longer than in either other group ( P < 0.001). The crude parameters of host response to tumour, body, spleen and mesenteric lymph node weight were recorded and the latter two indexed to body weight. The body weight of tumour and control rats increased significantly with time ( P < 0.04). The spleen and mesenteric node indices were significantly ( P < 0.04) greater in tumour than control rats and were varied by recurrent tumour growth and by the adjuvant treatment administered postoperatively.

scholarly journals A possible relation between dietary zinc and cAMP in the regulation of tumour cell proliferation in the rat

1988 ◽  
Vol 59 (3) ◽  
pp. 437-442 ◽  
Author(s):  
Noel S. Skeef ◽  
John R. Duncan
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Line ◽  
Tumour Cell ◽  
Tumour Growth ◽  
Zn Deficiency ◽  
Regenerating Liver ◽  
Small Reduction ◽  
Dietary Zinc ◽  
Camp Concentration

1. The possibility of an effect of zinc on the rate of tumour cell division, mediated through a regulation of cellular cAMP concentration, was investigated in the present study in rats.2. Dietary Zn deficiency (< 1·5 mg Zn/kg) but not Zn excess (500 mg Zn/kg) resulted in an increased cAMP concentration in transplanted hepatoma cells. Neither treatment had any effect on the cAMP concentration in regenerating liver or normal resting liver. Both the deficient and excess Zn diets resulted in a small reduction in tumour growth (not statistically significant).3. The results seem to indicate that the relation investigated in the present study does not apply in the cell line used.

scholarly journals Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Valter Tadeu Boldarine ◽  
Ellen Joyce ◽  
Amanda Paula Pedroso ◽  
Mônica Marques Telles ◽  
Lila Missae Oyama ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Neutral Lipids ◽  
Saturated Fat ◽  
Metabolic Effects ◽  
Cholesteryl Esters ◽  
Ovx Rats ◽  
Lipid Species ◽  
Retroperitoneal White Adipose Tissue ◽  
Induced Changes

AbstractMenopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17β-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-β indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-β index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono–Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono–Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono–Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.

WING MOVEMENTS AND LIFT REGULATION IN THE FLIGHT OF DESERT LOCUSTS

1993 ◽  
Vol 182 (1) ◽  
pp. 57-69 ◽  
Author(s):  
M. Wortmann ◽  
W. Zarnack
Keyword(s):  
Body Weight ◽  
Unsteady Aerodynamics ◽  
Movement Patterns ◽  
The Body ◽  
Three Dimensions ◽  
Body Angle ◽  
Wing Movement ◽  
Induced Changes ◽  
Lift Body

1. We simultaneously recorded lift/body weight, flight speed, body angle and 12 variables of wing movement for locusts performing tethered long-term flight with low movement scatter. The movements of the forewings and hindwings were recorded in three dimensions by means of miniature induction coils. 2. By adjusting the body angle, we could reproducibly manipulate lift generation as a consequence of induced changes in the wings' movement patterns. We were therefore able to analyse various relationships between the movement patterns and lift. 3. The most prominent variations of kinematic variables were observed for the forewing movements. The relative lift and the steady angle of pitch were positively correlated but there was a negative correlation between relative lift and pitching amplitude. We found no correlation between relative lift and flapping amplitude. Our results seem to correspond to a new theory about unsteady aerodynamics of oscillating aerofoils. 4. We sometimes observed variations in lagging. 5. The forewing downstroke was delayed by 0–8 ms following the hindwing downstroke. Relative lift was positively correlated to this delay.

Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet

2004 ◽  
Vol 286 (2) ◽  
pp. R390-R397 ◽  
Author(s):  
D. N. D'Souza ◽  
Y. Zhang ◽  
F. Garcia ◽  
G. Battaglia ◽  
L. D. Van de Kar
Keyword(s):  
Body Weight ◽  
Control Diet ◽  
Hormone Secretion ◽  
Significant Loss ◽  
Tryptophan Depletion ◽  
Deficient Diet ◽  
Hormone Responses ◽  
Plasma Hormones ◽  
Induced Changes ◽  
The Impact

Tryptophan depleting protocols are commonly used to study the role of serotonin in mood disorders. The present study examined the impact of a tryptophan-deficient diet and fluoxetine on the serotonergic regulation of neuroendocrine function and body weight. We hypothesized that the regulation of postsynaptic 5-HT1A receptors is dependent on the levels of 5-HT in the synapse. Rats on a control or a tryptophan-deficient diet received daily injections of saline or fluoxetine (5 or 10 mg·kg-1·day-1 ip) from day 7 to day 21. The tryptophan-deficient diet produced a 41% reduction in the level of 5-HT but no change in the density of [3H]paroxetine-labeled 5-HT transporters. Treatment with fluoxetine inhibited the gain in weight in rats maintained on the control diet. The tryptophan-deficient diet produced a significant loss in body weight that was not significantly altered by treatment with fluoxetine. Treatment with fluoxetine produced a dose-dependent desensitization of hormone responses to injection of the 5-HT1A receptor agonist (±)8-hydroxy-2-(di- n-propylamino)tetralin ((±)8-OH-DPAT). The tryptophan-deficient diet produced an increase in the basal levels of corticosterone but did not alter the basal levels of ACTH or oxytocin. Also, this diet inhibited the magnitude of 8-OH-DPAT-induced increase in plasma levels of ACTH and oxytocin but did not impair the ability of fluoxetine to desensitize the 5-HT1A receptor-mediated increase in plasma hormones. These data suggest that a reserve of 5-HT enables fluoxetine to desensitize postsynaptic 5-HT1A receptors in the hypothalamus. In conclusion, the profound physiological changes induced by tryptophan depletion may complicate the interpretation of studies using this experimental approach.

Immunotoxicity of an Electrochemically Fluorinated Aqueous Film-Forming Foam

2020 ◽  
Vol 178 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Carrie A McDonough ◽  
Chastity Ward ◽  
Qing Hu ◽  
Samuel Vance ◽  
Christopher P Higgins ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Perfluorooctane Sulfonate ◽  
Positive Control ◽  
Film Forming ◽  
Body Weights ◽  
Specific Antibody Production ◽  
Fire Suppressants ◽  
Contaminated Drinking Water ◽  
Induced Changes

Abstract Aqueous film-forming foams (AFFFs) are complex per- and polyfluoroalkyl substance (PFAS)-containing mixtures used extensively as fire suppressants. AFFF-impacted groundwater and surface water have contaminated drinking water with PFASs in many communities, raising concerns about health effects from drinking water exposures. As individual PFASs have been identified as immune hazards, the immunotoxicity of complex PFAS mixtures is also a concern. Adult female and male C57BL/6 mice were given a commercial AFFF formulation for 10 days via gavage; administered dose was based on combined content of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) measured in the formulation (0, 1.88, 3.75, 7.5, or 10 mg PFOS+PFOA/kg body weight). A PFOA positive control of 7.5 mg/kg body weight was also given. Compared with the 0 mg/kg group, the following changes were noted: Body weights of males exposed to 7.5 and 10 mg PFOS+PFOA/kg were reduced by 15%, on average; female body weights did not differ. Average relative liver weights were increased 50%–200% in males and 37.5%–193% in females and liver peroxisome proliferation was increased 2- to 12-fold in all doses of both sexes. Antigen-specific antibody production was suppressed, on average, by 13% in males and by 12.4% in females across all doses. Spleen cellularity and lymphocyte subpopulations did not differ by dose for either sex. Our data indicate that though this complex PFAS mixture contained fairly low PFOA content, it induced changes in C57BL/6 mice similar to changes induced by PFOA alone, likely due to the presence of PFOS and many other PFASs.

Sex differences in central adrenoreceptor-mediated vasopressin response to hemorrhage

1991 ◽  
Vol 260 (5) ◽  
pp. E780-E786 ◽  
Author(s):  
J. D. Stone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Sex Differences ◽  
Mean Arterial Blood Pressure ◽  
Intracerebroventricular Injection ◽  
Arterial Blood ◽  
Plasma Vasopressin ◽  
Vasopressin Secretion ◽  
Blood Pressure Responses ◽  
Induced Changes

Hemorrhage-induced changes in the plasma vasopressin concentration and mean arterial blood pressure (MABP) were studied in conscious rats of both sexes with and without central alpha 1-adrenoreceptor blockade. Rats were subjected to two sequential hemorrhages (H1 and H2), each 0.8% of body weight after an intracerebroventricular injection of the alpha 1-adrenoreceptor antagonist corynanthine or of vehicle. H1 stimulated vasopressin secretion more in proestrous females than in males; there were no significant sex-related differences in responses to H2. Corynanthine pretreatment attenuated the vasopressin response to H2 in males, potentiated this response in proestrous females, but had no effect in estrous females. MABP decreased after H1 in all female groups and in corynanthine-pretreated males. After H2, all groups were hypotensive to the same extent. These data indicate that central alpha 1-adrenoreceptor-mediated pathways participate in vasopressin and blood pressure responses to hemorrhage, but their role is complex and is dependent on gender and on the phase of the estrous cycle.

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