NANO-BIOTECHNOLOGY AND ITS INNOVATIVE PERSPECTIVE IN DIABETES MANAGEMENT

2021 ◽  
Vol 21 ◽  
Author(s):  
Jigar Raval ◽  
Riddhi Trivedi ◽  
Sonali Suman ◽  
Arvind Kukrety ◽  
Prajesh Prajapati
Keyword(s):  
Cellular Uptake ◽  
Glucose Homeostasis ◽  
Diabetes Management ◽  
The Body ◽  
Paracellular Transport ◽  
Specific Gene ◽  
Future Prospects ◽  
Transcellular Transport ◽  
Routes Of Administration ◽  
Two Stages

: Diabetes occurs due to the imbalance of glucose in the body known as glucose homeostasis, thus leading to metabolic changes in the body. The two stages hypoglycemia or hyperglycemia classify diabetes into various categories. Various bio-nanotechnological approaches are coupled up with nano particulates, polymers, liposome, various gold plated and solid lipid particulates, regulating transcellular transport, non specific cellular uptake, and paracellular transport, leading to oral, trans-dermal , pulmonary, buccal , nasal , specific gene oriented administration to avoid the patient’s non compliance with the parental routes of administration. Phytochemicals are emerging strategies for the future prospects of diabetes management.

Movement of Hydroxyurea Across Cell Membranes Is Mediated by Specific Solute Carrier (SLC) Transporters.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2575-2575
Author(s):  
Aisha L. Walker ◽  
Ryan M Franke ◽  
Alex Sparreboom ◽  
Russell E. Ware
Keyword(s):  
Vector Control ◽  
Cellular Uptake ◽  
Organic Cation ◽  
Organic Anion ◽  
Fold Increase ◽  
The Body ◽  
Transcellular Transport ◽  
Slc Transporters ◽  
Solute Carrier

Abstract Abstract 2575 Poster Board II-552 Background: Hydroxyurea is the only FDA-approved drug for the treatment of sickle cell anemia (SCA) in adults. Hydroxyurea increases fetal hemoglobin, decreases hospitalizations and painful events, and reduces mortality. With an oral bioavailability of > 90%, hydroxyurea is rapidly absorbed and distributed throughout the body. Though hydroxyurea has proven to be effective in treating SCA, there is considerable inter-patient variability observed in the pharmacokinetics and pharmacodynamics of hydroxyurea. Currently, mechanisms involved in the absorption, distribution, and elimination of hydroxyurea remain unclear. Recently, key transmembrane proteins have been identified as drug transporters due to their ability to move a variety of xenobiotic substances across cell membranes. Drug transporters are widely distributed throughout the body, and most are specific to certain substrates. Solute carrier (SLC) transporters in particular have been to shown to significantly impact drug pharmacokinetics by influencing the absorption, distribution, and elimination of specific drugs. The present study was designed to identify SLC transporters that may influence the absorption, distribution, and/or elimination of hydroxyurea in patients with SCA. Methods: In vitro studies using an equilibrium dialysis plate were performed to determine the amount of hydroxyurea that binds to human serum proteins. Transporter-mediated cellular uptake of hydroxyurea was determined in vitro by measuring [14C]-hydroxyurea accumulation in HEK293 cells and oocytes that overexpress organic anion transporters (OAT1-3), organic cation transporters (OCT1-3), organic cation/carnitine transporters (OCTN1-2), organic anion transporting polypeptides (OATP1A2/OATP1B1/OATP1B3), or vector control. LLC-PK1 cells that overexpress urea transporters A or B (UTA/UTB) were used to determine UTA/UTB mediated transcellular transport of hydroxyurea in transwell plates. The transport of [14C]-hydroxyurea from apical to basal or from basal to apical compartments was measured for the UTA/UTB overexpressing cells and compared to vector control. UTA and UTB mRNA expression was measured by real-time PCR of cDNA obtained from human tissue samples. Results: Protein binding assays showed that >76% of [14C]-hydroxyurea remained unbound to proteins in human serum containing hydroxyurea at concentrations ranging from 1.5μM to 500μM. The fraction of unbound hydroxyurea was similar using serum obtained from pediatric patients with SCA. In uptake studies, [14C]-hydroxyurea was a potent substrate for OATP1B3 with an approximately 2-fold increase in drug accumulation compared to control (p<0.001). In contrast, hydroxyurea was found to be a weak substrate for OCTN1, OCTN2, OATP1A2, and OATP1B1 with only a 1.3-fold increase in drug accumulation compared to control (p<0.04). Transcellular transport of hydroxyurea was increased 3- and 2-fold by UTA and UTB, respectively, compared to vector control demonstrating hydroxyurea to be a potent substrate for these transporters as well (p<0.02). When the urea transporter inhibitor dimethylurea was added, hydroxyurea transport by UTA and UTB-expressing cells was decreased to levels observed with the vector control. In real-time PCR assays, kidney, muscle, and small intestine were among human tissues with high expression of UTA mRNA, while prostate, brain, and bone marrow had high levels of UTB mRNA expression. Conclusion: Cellular uptake of hydroxyurea is mediated by active transport via specific SLC transporters OATP1B3, UTA and UTB, which are expressed in liver, kidney, brain, intestine, and blood cells. Studies to further characterize hydroxyurea transporters should improve our understanding of the pharmacokinetic and pharmacodynamic profiles of hydroxyurea used in clinical practice for patients with SCA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reproductive biology, embryonic development and matrotrophy in the phylactolaemate bryozoan Plumatella casmiana

2021 ◽  
Author(s):  
Julian Bibermair ◽  
Andrew N. Ostrovsky ◽  
Andreas Wanninger ◽  
Thomas Schwaha
Keyword(s):  
Embryonic Development ◽  
Embryo Sac ◽  
The Body ◽  
Transcellular Transport ◽  
Cell Contacts ◽  
Transmission Electron ◽  
Distal Side ◽  
Early Embryos ◽  
Mesoderm Formation ◽  
Cytoplasmic Processes

AbstractBryozoa is a phylum of aquatic, colonial suspension-feeders within the Lophotrochozoa. In the Phylactolaemata embryonic development occurs in an internal brood sac on the body wall accompanied by extraembryonic nutrition. Owing to previous contradictive descriptions, many aspects of their sexual reproduction require restudy. Consequently, this study analyses embryogenesis of the freshwater bryozoan Plumatella casmiana by serial sections, 3D reconstruction and transmission electron microscopy. Early embryos cleave and soon develop into blastulae with a small central cavity. The mesoderm forms by delamination starting from the distal side towards the proximal end. In later embryos two polypides form on the posterior side that ultimately will be covered by a ciliated mantle in the larva. Embryos increase in size during development and form temporary cell contacts to the embryo sac. Mesodermal cells of the embryo sac show signs of transcellular transport indicating that embryos are nourished by transferring nutrients from the maternal coelom towards the brood cavity. This study clarifies several details such as mesoderm formation and the onset of bud development. Embryos are connected to their respective embryo sacs by a variety of temporary cytoplasmic processes formed by both tissues during embryogenesis, including a ‘placental’ ring zone. Although ultrastructural data of these cell contacts are not entirely conclusive about their function, we suggest that embryos absorb nutrients via the entire surface. The close opposition of embryos to the embryo sac implies placentation as matrotrophic mode in phylactolaemate bryozoans, with embryo sacs acting as placental analogues.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

Lepeophtheirus salmonis (Krøyer, 1837): second nauplius and copepodid locomotor appendages, surface areas and possible appendage functions

Crustaceana ◽  
2013 ◽  
Vol 86 (13-14) ◽  
pp. 1695-1710 ◽  
Author(s):  
Susan E. Allen ◽  
A. G. Lewis
Keyword(s):  
Body Position ◽  
Ventral Surface ◽  
Total Surface Area ◽  
The Body ◽  
Lepeophtheirus Salmonis ◽  
Sinking Rate ◽  
Surface Areas ◽  
Thoracic Legs ◽  
Two Stages ◽  
Suitable Location

Locomotor appendage-body relationships were used to examine whether swimming or reduction in sinking rate is the more important function in the second nauplius and copepodid stages of Lepeophtheirus salmonis (Krøyer, 1837). Except for the similarity in swimming appendage surface areas without setae, the appendages of the two stages are morphologically distinct. Although the nauplius is smaller than the copepodid it has long slender appendages that, with setae, provide greater total surface area than the paddle-shaped copepodid thoracic legs. Copepodid thoracic legs are more similar to those used for swimming by planktonic copepods although with more limited propulsion capability. Naupliar appendages project from the body while copepodid appendages can be folded against the ventral surface, improving hydrodynamic flow as well as body position after attachment to a host. Both copepodid and naupliar appendages are of sufficient size that they should provide escape velocities of more than 100 mm ⋅ s−1. The nature and display of the naupliar appendages suggest they could be used to reduce sinking rate by as much as 64%, reducing the need to swim to maintain a suitable location in the water. Although copepodid thoracic legs could reduce sinking rate by over 40%, their position on the ventral surface and the nature of other appendages suggests a more important use, for orientation and attachment once a host is located.

Theoretical foundations and general provisions of autohemotherapy

1930 ◽  
Vol 26 (7) ◽  
pp. 118-124
Author(s):  
S. I. Sherman
Keyword(s):  
Morphological Changes ◽  
Scientific Basis ◽  
The Body ◽  
Practical Medicine ◽  
Routes Of Administration ◽  
Therapeutic Measures ◽  
Theoretical Foundations ◽  
Dosage Frequency

Currently, autohemotherapy takes one of the places of honor among; of our therapeutic measures and there is not a single area of ​​practical medicine where oisch is not applied. At the same time, this type of therapy still does not have an exact scientific basis; Thus, there are many different views on the essence of the action of this method, but there are still no precise indications and contraindications for the use of autohemotherapy for certain types of diseases, then the dosage, frequency of injections, their number, etc., vary sharply among different authors. we will review the following issues - the essence of the action of autohemotherapy, the dosage and frequency of injections, the reaction of the body (general, focal, local), the advantage of one or another method of using autoblood injections (intracutaneous, subcutaneous and intramuscular routes of administration) and, finally, morphological changes in blood during this method of treatment.

Modeling bid/no bid decisions using fuzzy fault tree

2018 ◽  
Vol 18 (1) ◽  
pp. 90-108 ◽  
Author(s):  
Mohamed Marzouk ◽  
Emad Mohamed
Keyword(s):  
Fault Tree ◽  
The Body ◽  
Final Decision ◽  
Extensive Literature ◽  
Willingness To Participate ◽  
Tree Model ◽  
Content Type ◽  
Proposed Model ◽  
Multiple Experts ◽  
Two Stages

Purpose Decisions by construction contractors to bid (or not to bid) require the thorough assessment and evaluation of factors relevant to the decision, as well as the quantification of their combined impact, to produce successful bid/no-bid decisions. The purpose of this study is to present a fuzzy fault tree model to assist construction contractors to more efficiently bid for future projects. Design/methodology/Approach The proposed model consist of two stages: first, identification of the factors that affect bidding decision using a questionnaire survey after an extensive literature review, and second, usage of the identified factors to build a fuzzy fault tree model to simulate the bidding decision. Findings A list of 15 factors that affect bid/no-bid decisions was identified. Analysis of factors revealed that the highest-ranking factors were related to financial aspects of the project. A case study is presented to demonstrate the capabilities of the model, and a fuzzy important analysis is performed on the basic events to demonstrate the differences between three contractors’ bid/no-bid decisions. The results reveal that there is variation between the decisions of each contractor based on their willingness to participate. Besides, the influence of evaluation factors on the final decision for each contractor is different. Originality/value The study contributes to the body of knowledge on tendering and bidding practices. The proposed model incorporated the fuzzy set theory, which suits human subjectivity. The proposed methodology overcomes the limitations of previous models as it can, using the linear pool opinion principle, combine and weigh the evaluations of multiple experts. In addition, the model is convenient for situations where historical data are not available.

THE MANAGEMENT OF THE CRITICALLY ILL CHILD WITH DEHYDRATION SECONDARY TO DIARRHEA

PEDIATRICS ◽  
1970 ◽  
Vol 45 (6) ◽  
pp. 1029-1036
Author(s):  
Laurence Finberg
Keyword(s):  
Diarrheal Disease ◽  
Oral Intake ◽  
The Body ◽  
Critical Stage ◽  
Water Losses ◽  
Subcutaneous Infusion ◽  
Routes Of Administration ◽  
Parenteral Route ◽  
Trained Personnel ◽  
Enteric Infections

Diarrhea and vomiting, which so frequently complicate diarrheal diseases, occur in a variety of disorders affecting infants. Although enteric infections cause these symptoms more often than all other diseases combined, noninfectious causes may occasionally also occur. While each cause may have specific other effects, the discussion here will deliberately be limited to the management of the physiologic disturbances that accompany excessive loss of water and salts from tile gastrointestinal tract. Etiologic considerations, however important they may be, will not be further pursued. This emphasis is appropriate since survival following critical dehydration depends far more upon the correction of the physiologic disturbance than upon the removal of the cause. A critical stage in diarrheal disease may be defined as occurring when a volume of fluid equal in mass to about 10% of the body weight has been lost over a period of a day or two. Clinically, this usually occurs shortly after anorexia or vomiting has precluded oral intake. At this stage of illness, parenteral fluid therapy should be employed. Oral intake should be curtailed during the early hours of therapy. The use of milk or other foods high in calories and solute complicates management by markedly increasing stool water losses. Even if severe undernutrition coexists with tile diarrhea, the first 6 to 8 hours should be a period of brief starvation; the parenteral glucose will provide emergency calories. Although such routes of administration as intragastric drip and subcutaneous infusion have been employed successfully, their usage should be restricted to places where a deficiency of supplies or trained personnel interdicts the preferred parenteral route—continuous intravenous infusion.

Recovery of 13C in breath from NaH13CO3 infused by gut and vein: effect of feeding

1989 ◽  
Vol 257 (3) ◽  
pp. E426-E438 ◽  
Author(s):  
R. A. Hoerr ◽  
Y. M. Yu ◽  
D. A. Wagner ◽  
J. F. Burke ◽  
V. R. Young
Keyword(s):  
Statistical Significance ◽  
The Body ◽  
Co2 Production ◽  
Base Line ◽  
Experimental Diet ◽  
Factors Affecting ◽  
Routes Of Administration ◽  
Line P ◽  
Male Subjects ◽  
Atom Percent Excess

Estimates of substrate oxidation obtained from appearance of 13C or 14C from tracers in breath must be corrected for retention of labeled carbon in the body. We aimed to determine the effect of a defined experimental diet and metabolic status on recovery of infused Na [13C]bicarbonate in breath. Six healthy male subjects consumed an experimental diet for 7 days before receiving a continuous infusion of formula without tracer on day 8 and received either an intragastric (ig) or intravenous (iv) infusion of Na [13C]bicarbonate on day 9 or 11 during a 4-h postabsorptive (PA), 4-h continuously fed period. A trend toward increasing PA breath enrichment during the first 7 diet days approached statistical significance (P = 0.051), whereas breath enrichments measured 3 h postbreakfast were consistently higher than PA values throughout and did not change over the 7-day period. Breath enrichments during a 4-h continuous ig infusion of formula without tracer on day 8 rose 2.0 +/- 0.5 atom percent excess (APE).10(-3) above base line (P less than 0.001, ANOVA). In the tracer studies, breath enrichments were similar for the ig and iv routes of tracer infusion. For the ig infusion the fraction of infused Na [13C]bicarbonate recovered in breath as 13CO2 was 0.74 +/- 0.02 for the PA period and 0.79 +/- 0.02 for the fed period. For the iv infusion the fraction recovered was 0.70 +/- 0.04 for the PA period and 0.82 +/- 0.03 for the fed period. Fractional recoveries were not significantly different for ig and iv routes of administration but were different for PA and fed periods (P less than 0.0001, 2-way ANOVA). The fractional recoveries for the fed period obtained here were similar to the value 0.81 reported in a number of other studies. Recovery of tracer in breath increased linearly with O2 uptake and CO2 production, suggesting that factors affecting respiratory gas exchange may alter recovery. We conclude that the primary factor determining label recovery is the immediate and recent nutritional status of the host.

THE HALF-LIFE OF PROGESTERONE IN THE PERIPHERAL BLOOD OF A EWE AT TWO STAGES OF GESTATION

1962 ◽  
Vol 25 (3) ◽  
pp. 369-374 ◽  
Author(s):  
R. V. SHORT ◽  
J. G. ROWELL
Keyword(s):  
Peripheral Blood ◽  
Half Life ◽  
The Body ◽  
Progesterone Production ◽  
The Difference ◽  
Two Stages

SUMMARY [4-14C]Progesterone (10 μc, 154 μg.) was injected intravenously into a Suffolk ewe on the 115th day of gestation, and again a few hours before parturition. Within 5 min. of the injection, only about 1% of the radioactive progesterone was present in the circulating blood. During the ensuing 25 min., the fall in concentration was approximately exponential, the estimated half-lives being 7·3 ± 1·2 min. at day 115 and 8·1 ± 0·6 min. just before lambing. The difference between these half-lives is not significant. Subject to a number of assumptions, these half-lives may be used as a measure of the rate at which progesterone is metabolized in the body. It is concluded that there are no pronounced changes in the rate of progesterone production or metabolism during the course of pregnancy in the ewe.

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