scholarly journals Restoring ventilatory control using an adaptive bioelectronic system

2018 ◽  
Author(s):  
Ricardo Siu ◽  
James J Abbas ◽  
Brian K Hillen ◽  
Jefferson Gomes ◽  
Stefany Coxe ◽  
...  
Keyword(s):  
Closed Loop ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
Stimulation Parameters ◽  
Sprague Dawley Rats ◽  
Volume Profile ◽  
Stimulation Pattern ◽  
Stimulation Of

Ventilatory pacing via electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially-available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath volume profile on a breath-by-breath basis. In vivo studies in anesthetized intact and C2-hemisected male Sprague-Dawley rats indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed prior to injury (p=0.39). The closed-loop controller was developed and parametrized in a computational testbed prior to in-vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.

Superoxide stimulates NaCl absorption by the thick ascending limb

2002 ◽  
Vol 283 (5) ◽  
pp. F957-F962 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Jeffrey L. Garvin
Keyword(s):  
Xanthine Oxidase ◽  
In Vivo Studies ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Cytotoxic Effects ◽  
Nacl Absorption ◽  
Enhanced Chemiluminescence ◽  
Sprague Dawley Rats

The thick ascending limb of the loop of Henle (THAL) plays an important role in the regulation of NaCl and water reabsorption. In vivo studies have shown that the free radical superoxide (O[Formula: see text]) stimulates Na and water reabsorption by the kidney. However, it is not known whether O[Formula: see text]regulates transport along the nephron in general or in the THAL specifically. We hypothesized that O[Formula: see text] stimulates THAL NaCl reabsorption. Cl absorption was measured in isolated, perfused THALs from Sprague-Dawley rats. First, we tested whether extracellular O[Formula: see text] stimulates Cl absorption. Addition of the O[Formula: see text]-generating system xanthine oxidase/hypoxanthine increased Cl absorption from 112.7 ± 12.0 to 146.2 ± 13.9 pmol · mm−1· min−1, a 33% increase ( P < 0.03). When superoxide dismutase (300 U/ml) was present in the bath, addition of xanthine oxidase/hypoxanthine did not significantly increase Cl absorption (116.9 ± 13.8 vs. 102.5 ± 8.5 pmol · mm−1· min−1). Furthermore, adding 200 nM H2O2to the bath did not significantly affect Cl absorption (from 130.3 ± 13.7 to 125.3 ± 19.6 pmol · mm−1· min−1). Because extracellular O[Formula: see text] stimulated Cl absorption, we next tested whether endogenously produced O[Formula: see text] could stimulate transport. Under basal conditions, THALs produced detectable amounts of O[Formula: see text], as measured by lucigenin-enhanced chemiluminescence. Adding the O[Formula: see text] scavenger tempol to the bath decreased Cl absorption from 198.1 ± 35.4 to 132.4 ± 23.5 pmol · mm−1· min−1, a 31% decrease ( P < 0.02). To make sure tempol was not exerting cytotoxic effects, we tested whether its effect was reversible. With tempol in the bath, Cl absorption was 117.2 ± 9.3 pmol · mm−1· min−1. Sixty minutes after tempol was removed from the bath, Cl absorption had increased to 149.2 ± 9.1 pmol · mm−1· min−1( P < 0.05). We concluded that both exogenous and endogenous O[Formula: see text] stimulate THAL NaCl absorption. To our knowledge, these are the first data showing a direct effect of O[Formula: see text] on nephron transport.

scholarly journals Kinetics of insulin secretion to acute, repetitive stimulation of islets in vivo in sprague dawley rats

Islets ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. 10-17 ◽  
Author(s):  
JianLiang Chen ◽  
Aparna Nittala ◽  
Shouguo Gao ◽  
Soumitra Ghosh ◽  
Xujing Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Repetitive Stimulation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Kinetics Of ◽  
Stimulation Of

Rapamycin blunts nutrient stimulation of eIF4G, but not PKCε phosphorylation, in skeletal muscle

2007 ◽  
Vol 293 (1) ◽  
pp. E188-E196 ◽  
Author(s):  
Thomas C. Vary ◽  
Joshua C. Anthony ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball ◽  
Christopher J. Lynch
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Target Of Rapamycin ◽  
Initiation Factor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Meal Feeding ◽  
Eukaryotic Initiation Factor 4G ◽  
Mtor Complex 1 ◽  
Stimulation Of

Phosphorylation of eukaryotic initiation factor 4G (eIF4G) is hypothesized to be an important contributor to the stimulation of protein synthesis in skeletal muscle following meal feeding. The experiments reported herein examined the potential role for a rapamycin-sensitive signaling pathway in mediating the meal feeding-induced elevations in phosphorylation of eIF4G. Gastrocnemius from male Sprague-Dawley rats trained to consume a meal consisting of rat chow was sampled prior to and following 3 h of having the meal provided in the presence or absence of treatment with rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Pretreatment with rapamycin prevented the feeding-induced phosphorylation of mTOR, eIF4G, and S6K1 but only partially attenuated the shift in 4E-BP1 into the γ-form. In contrast, the feeding-induced increase in phosphorylation of PKCε was not reduced by rapamycin. Rapamycin also prevented the augmented association of eIF4G with eIF4E and the decreased association of eIF4E with 4E-BP1. Similar findings were observed in gastrocnemius from animals after oral administration of leucine. Perfusion of gastrocnemius with medium containing rapamycin partially prevented the leucine-induced increase in phosphorylation of eIF4G. Thus, rapamycin attenuated a feeding- or leucine-induced phosphorylation of eIF4G in skeletal muscle both in vivo and in situ. The latter observation implies that the effects observed with rapamycin were the result of modulation of skeletal muscle signaling mechanisms responsible for eIF4G phosphorylation.

Y1- and α1-receptor control of basal hindlimb vascular tone

2004 ◽  
Vol 287 (1) ◽  
pp. R228-R233 ◽  
Author(s):  
Dwayne N. Jackson ◽  
Earl G. Noble ◽  
J. Kevin Shoemaker
Keyword(s):  
Vascular Tone ◽  
Receptor Activation ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
Vascular Conductance ◽  
Flow Profiles ◽  
Sprague Dawley Rats ◽  
Differential Flow

The role of endogenous Y1-receptor activation on skeletal muscle vasculature under baseline conditions is currently debated and no in vivo studies have been performed to address this issue. Therefore, this study was designed to address the effect of Y1-receptor and/or α1-adrenoceptor antagonism on basal hindlimb vascular conductance in male Sprague-Dawley rats in vivo. Left hindlimb vascular conductance, carotid artery mean arterial pressure, and heart rate were measured during low volume infusion of N2-(diphenylacetyl)- N-[(4-hydroxyphenyl)methyl]-d-arginine amide (BIBP3226; 100 μg/kg), prazosin (20 μg/kg), and combined blockade to the left hindlimb. Vascular conductance increased 1.5 ± 0.5 μl·min−1·mmHg−1 with BIBP3226 infusion, 1.7 ± 0.5 μl·min−1·mmHg−1 with prazosin infusion, and 4.8 ± 1.0 μl·min−1·mmHg−1 with combined blockade ( P < 0.05). Interestingly, systolic vascular conductance increased in all three conditions, but diastolic vascular conductance only increased in the two conditions where BIBP3226 was present. These data indicate that Y1-receptor activation plays an important role in the regulation of vascular conductance in the resting rat hindlimb. Furthermore, this effect was of the same magnitude as the α1-adrenoceptor contribution. The differential flow profiles following α1 blockade with and without Y1-receptor blockade supports local differences in receptor distribution.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

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 Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

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