Differential Modulation of Erythrogenic Effects of EPO by Prolonged Administration of Glucocorticoids.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1733-1733
Author(s):  
Zili He ◽  
Maged Khalil ◽  
Srinivas Kodali ◽  
Seema Naik ◽  
Chenthilmuragan Rathnasabapathy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Combined Treatment ◽  
Control Treatment ◽  
Prolonged Treatment ◽  
Sprague Dawley ◽  
Research Committee ◽  
Interesting Phenomenon ◽  
In Vivo Effects

Abstract Glucocorticoids have either stimulatory or inhibitory effects on erythropoesis depending upon the timing and the dosage of their administration. We previously reported cases of enhanced hematopoetic recovery in response to erythropoietin (Epo; Procrit) in patients receiving prolonged treatment of glucocortcoids. To examine the differential roles of glucocorticoids on erythropoiesis in chronic settings, we use a murine model in current study and evaluate erythropoietic responses to Epo for rats receiving higher (loading) or lower (maintenance) dosages of dexamethasone(Dex) for a prolonged period of time. Commercially-obtained adult Sprague-Dawley rats were assigned randomly to DEX, EPO, DEX+EPO, or control groups, and maintained at conditions approved by the institutional Animal Care and Research Committee. Rats in the EPO or DEX+EPO groups received subcutaneous injection of Epo at 70 units/100 grams body weight, once a week, for five week. The animals in the DEX or DEX+EPO group were both divided into two subgroups receiving injection of Dex at either higher doses of 0.4mg/350 grams body weight, or lower doses of 0.02 mg/350 grams body weight, three times a week, for five weeks. The animals were sacrificed at the end of study and peripheral blood and bone marrow were used to evaluate levels of erythropoiesis. Weekly administration of Epo (70 units/100 grams body weight) for five weeks produced enhanced erythropoiesis in the EPO group, resulting in an increase of 10.6% in RBC, and 15.3% increase in hemoglobin (Hb), compared to control. Treatment of rats with higher dosage (0.4 mg/350 g, three times a week for five weeks) of dexamethasone increased RBC and Hb by 3% and 2%, respectively, when compared with controls. Combined treatment of Epo and dexamethasone at the higher dosage enhanced the erythropoiesis, and increased RBC and Hb by 20% and 23%, respectively. In contrast, treatment of rats with a lower maintenance dosage of 0.02 mg/350 g body weight, three times a week for five weeks, peripheral RBC and Hb levels were dropped by 7% and 6%, respectively. Combination of Epo and the lower dosage of dexamethasone could only generate an increase in RBC and Hb of 10% each, displaying suppressing effect of dexamethasone at lower dosage. Bone marrow biopsy revealed hypocellularity in all groups using dexamethasone. Marrow iron staining was performed and ruled out any iron deficiency in all groups. These results suggest that glucocorticoids modulate erythropoisis in two ways depending on concentrations, enhancing erythropoiesis greatly at loading dosage while suppressing it at lower maintenance doses. Our data, together with our clinical observations, present an interesting phenomenon of cross modulation of the two widely used medications, Epo and glucocorticoids. It certainly warrants further investigation of involving pathways at molecular levels. In Vivo Effects of Dexamethasone on Epo stimulated erythropoiesis In Vivo Effects of Dexamethasone on Epo stimulated erythropoiesis

Sinusoidal Cells in Bone Marrow Take Up BSA-Au Conjugates in the Presence of an Artificial Blood Substitute

1985 ◽  
Vol 43 ◽  
pp. 700-701
Author(s):  
J.S. Geoffroy ◽  
R.P. Becker
Keyword(s):  
Bone Marrow ◽  
Los Angeles ◽  
Iliac Artery ◽  
Blood Substitute ◽  
Sprague Dawley ◽  
Coated Pits ◽  
Sinusoidal Cells ◽  
Artificial Blood ◽  
Left Common Iliac Artery

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.

scholarly journals Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2223
Author(s):  
Manon Dominique ◽  
Nicolas Lucas ◽  
Romain Legrand ◽  
Illona-Marie Bouleté ◽  
Christine Bôle-Feysot ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Molecular Mimicry ◽  
Potential Effect ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
E Coli ◽  
In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

scholarly journals In VivoEffects of Leptin-Related Synthetic Peptides on Body Weight and Food Intake in Female ob/obMice: Localization of Leptin Activity to Domains Between Amino Acid Residues 106–140*

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1413-1418 ◽  
Author(s):  
Patricia Grasso ◽  
Matthew C. Leinung ◽  
Stacy P. Ingher ◽  
Daniel W. Lee
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Amino Acid ◽  
Food Intake ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Amino Acid Residues ◽  
Inactive Form ◽  
In Vivo Effects

Abstract In C57BL/6J ob/ob mice, a single base mutation of the ob gene in codon 105 results in the replacement of arginine by a premature stop codon and production of a truncated inactive form of leptin. These observations suggest that leptin activity may be localized, at least in part, to domains distal to amino acid residue 104. To investigate this possibility, we synthesized six overlapping peptide amides corresponding to residues 106–167 of leptin, and examined their effects on body weight and food intake in female C57BL/6J ob/ob mice. When compared with vehicle-injected control mice, weight gain by mice receiving 28 daily 1-mg ip injections of LEP-(106–120), LEP-(116–130), or LEP-(126–140) was significantly (P < 0.01) reduced with no apparent toxicity. Weight gain by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167) was not significantly different from that of vehicle-injected control mice. The effects of LEP-(106–120), LEP-(116–130), or LEP-(126–140) were most pronounced during the first week of peptide treatment. Within 7 days, mice receiving these peptides lost 12.3%, 13.8%, and 9.8%, respectively, of their initial body weights. After 28 days, mice given vehicle alone, LEP-(136–150), LEP-(146–160), or LEP-(156–167) were 14.7%, 20.3%, 25.0%, and 24.8% heavier, respectively, than they were at the beginning of the study. Mice given LEP-(106–120) or LEP-(126–140) were only 1.8% and 4.2% heavier, respectively, whereas mice given LEP-(116–130) were 3.4% lighter. Food intake by mice receiving LEP-(106–120), LEP-(116–130), or LEP-(126–140), but not by mice receiving LEP-(136–150), LEP-(146–160), or LEP-(156–167), was reduced by 15%. The results of this study indicate 1) that leptin activity is localized, at least in part, in domains between residues 106–140; 2) that leptin-related peptides have in vivo effects similar to those of native leptin; and 3) offer hope for development of peptide analogs of leptin having potential application in human or veterinary medicine.

Abstract 2838: Bone Marrow Mesenchymal Stem Cells Differentiated into Beating Cardiomyocytes In Vivo and Improved Myocardial Function

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tong Wang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Min-shan Tsai ◽  
Max Harry Weil
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Myocardial Function ◽  
Phosphate Buffer Solution ◽  
Sprague Dawley ◽  
Buffer Solution ◽  
Marrow Mesenchymal Stem Cells ◽  
And Control

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)

In Vivo Effects of Human Bone Marrow Mesenchymal Stromal Cells on the Development of Experimental B16 Melanoma in Mice

2020 ◽  
Vol 168 (4) ◽  
pp. 561-565 ◽  
Author(s):  
V. N. Petrov ◽  
E. V. Isaeva ◽  
S. E. Ulyanenko ◽  
E. E. Beketov ◽  
E. M. Yatsenko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
B16 Melanoma ◽  
Human Bone ◽  
Human Bone Marrow ◽  
In Vivo Effects

scholarly journals Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates.

1987 ◽  
Vol 165 (4) ◽  
pp. 941-948 ◽  
Author(s):  
K Welte ◽  
M A Bonilla ◽  
A P Gillio ◽  
T C Boone ◽  
G K Potter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
White Blood Cells ◽  
Chemotherapeutic Agents ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Radiation Induced ◽  
Peripheral White Blood Cells ◽  
In Vivo Effects ◽  
Stimulating Factor

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.

scholarly journals Effect of Chemical Protection and Bone Marrow Treatment on Radiation Injury in Mice

Blood ◽  
1958 ◽  
Vol 13 (7) ◽  
pp. 665-676 ◽  
Author(s):  
PAUL URSO ◽  
C. C. CONGDON ◽  
D. G. DOHERTY ◽  
RAYMOND SHAPIRA
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Radiation Injury ◽  
Combined Treatment ◽  
X Rays ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Hematopoietic Organs ◽  
X Irradiation ◽  
Bone Marrow Granulocytes

Abstract MEG (prepared from 9.0 mg. of AET) significantly modified the response of the bone marrow, peripheral blood leukocytes, spleen, thymus, body weight, hematocrit, and histology of the hematopoietic organs to lethal (900 r) and sublethal (450 r) x-irradiation in CAF1 mice. MEG reduced the effect of 900 r on the bone marrow, granulocytes of the blood, hematocrit, spleen, thymus, and body weight by a factor of approximately two. Combined treatment (MEG and isologous bone marrow) of mice exposed to 900 r of x-rays demonstrated that MEG is primarily responsible for preventing the early destruction of the bone marrow, but bone marrow injection was primarily responsible for causing a more rapid recovery of the bone marrow. In mice receiving combined treatment, recovery of the leukocytes and spleen was primarily influenced by the bone marrow injection; whereas recovery of the thymus and body weight was primarily influenced by MEG. The hematocrit values were normal after combined treatment.

scholarly journals Lycopene restores trace element levels in ochratoxin A-treated rats

2017 ◽  
Vol 68 (2) ◽  
pp. 135-141
Author(s):  
Saziye Sezin Palabiyik ◽  
Pinar Erkekoglu ◽  
Murat Kızılgun ◽  
Gonul Sahin ◽  
Belma Kocer-Gumusel
Keyword(s):  
Trace Element ◽  
Ochratoxin A ◽  
Absorption Spectrometry ◽  
Mechanisms Of Action ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Trace Element Levels ◽  
Zinc Levels ◽  
In Vivo Effects

AbstractThis study was designed to investigate the in vivo effects of ochratoxin A (OTA) and/or lycopene on the levels of selenium, zinc, and copper in the liver, kidneys, and testes of male Sprague-Dawley rats. The rats were treated with OTA (0.5 mg kg-1day-1) and/or lycopene (5 mg kg-1day-1) by gavage for 7 or 14 days. Trace element levels were measured by atomic absorption spectrometry. OTA significantly lowered selenium (20 % in the liver, 17 % in the kidney, and 40 % in the testis), zinc (24 % in the liver, 23 % in the kidney, and 26 % in the testis), and copper levels (40 % in the liver and 10 % in the kidney). Lycopene alone did not affect the trace element levels in any of the organs. In combination with OTA, however, it significantly restored liver, kidney, and testis selenium and zinc levels compared to the group treated with OTA alone. Our results have confirmed that depletion of trace elements in different organs is one of the mechanisms of action of OTA. They also suggest that lycopene interferes with this depleting effect and restores trace element levels, the implications of which need to be further investigated.

scholarly journals The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

2000 ◽  
pp. 273-277 ◽  
Author(s):  
D Hofer ◽  
M Raices ◽  
K Schauenstein ◽  
S Porta ◽  
W Korsatko ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Receptor Agonist ◽  
Wistar Rats ◽  
Type Ii ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
In Vivo Effects

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.

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