Weight‐based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups ‐ A microdialysis porcine study

Green tea, which has higher concentrations of polyphenols than other teas, has been correlated with reduced risk of various malignancies with most data supporting a potential protective role in prostate neoplasia. Preclinical studies over the last 25 years implicate constituent green tea catechins, epigallocatechin-3-gallate (EGCG) being the predominant form, as the main mechanistic ingredient in the observed biologic effects, which vary from proapoptotic effects to inhibition of androgen receptor and signal transduction pathways. There have been few prospective clinical trials of green tea polyphenols (GTP), especially with well-characterized formulations and doses. Although there have been hints of beneficial clinical activity in prostate neoplasia, other studies have raised concerns about the limited bioavailability and very low target-tissue concentrations of GTPs. At present there is no proven role for GTP supplementation in the prevention of genitourinary (GU) malignancies, but novel GTP formulations and further clinical testing may still support a future for GTP supplementation in GU cancer prevention.

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Feasibility of Using Half-Life Multipliers To Estimate Extended Withdrawal Intervals following the Extralabel Use of Drugs in Food-Producing Animals

Journal of Food Protection ◽

10.4315/0362-028x-67.3.555 ◽

2004 ◽

Vol 67 (3) ◽

pp. 555-560 ◽

Cited By ~ 16

Author(s):

R. GEHRING ◽

R. E. BAYNES ◽

A. L. CRAIGMILL ◽

J. E. RIVIERE

Keyword(s):

Drug Use ◽

Half Life ◽

Animal Origin ◽

Target Tissue ◽

Tissue Concentrations ◽

Target Animal ◽

Alternative Method ◽

Food Of Animal Origin ◽

Simple Alternative ◽

Medicinal Drug

Under the Animal Medicinal Drug Use Clarification Act of 1994, veterinarians are legally allowed to use drugs in food-producing animals in an extralabel manner. This could potentially lead to violative residues in food of animal origin. It is therefore essential that an appropriately extended withdrawal interval be established. Ideally, these extended withdrawal intervals should be calculated on the basis of the tissue half-life of the drug in the target animal. However, these data are not readily available for all drugs of extralabel use in food-producing animals. For this reason, the use of a half-life multiplier has been proposed as a simple alternative method to estimate the effective tissue half-life of a drug. Extended withdrawal intervals, estimated using various half-life multipliers, were compared with the withdrawal intervals calculated using actual tissue half-lives. For the group of drugs investigated, a half-life multiplier of 5 resulted in estimates of extended withdrawal intervals that were potentially inadequate to prevent violative tissue residues for drugs that had relatively long tissue half-lives, high tolerances, or both. This is possibly because fewer half-lives are required for these drugs to reach the target tissue concentrations following administration at label doses. Use of a smaller half-life multiplier (in this case 3) is therefore suggested to ensure that extended withdrawal intervals are adequate to prevent violative tissue residues.

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Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye

British Journal of Ophthalmology ◽

10.1136/bjo.81.1.72 ◽

1997 ◽

Vol 81 (1) ◽

pp. 72-75 ◽

Cited By ~ 5

Author(s):

K. Ichien ◽

T. Yamamoto ◽

Y. Kitazawa ◽

A. Oguri ◽

H. Ando ◽

...

Keyword(s):

Mitomycin C ◽

Target Tissue ◽

Tissue Concentrations ◽

Rabbit Eye

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Effect of Acupuncture on Target Tissue Distribution of Schisandra lignans

Acupuncture in Medicine ◽

10.1136/acupmed-2012-010266 ◽

2013 ◽

Vol 31 (2) ◽

pp. 207-213 ◽

Cited By ~ 4

Author(s):

Tu-Lin Lu ◽

Xiao-Yan Wu ◽

Yu Song ◽

Hao Chen ◽

Bin Xu ◽

...

Keyword(s):

Synergistic Effect ◽

Tissue Distribution ◽

High Performance ◽

Rat Tissues ◽

Target Tissue ◽

Schisandra Chinensis ◽

Tissue Concentrations ◽

Practical Strategy ◽

Long Time ◽

Initial Hypothesis

Background Recently, the combination of acupuncture and Chinese medicine as a practical strategy to treat diseases is receiving considerable attention worldwide as they are usually found to exhibit intriguing therapeutic effectiveness. The current study aimed to study the adjunct effect of acupuncture on target tissue distribution of schisandra lignans when acupuncture is combined with Schisandra chinensis. Methods A simple and reliable high performance liquid chromatography-electrospray tandem-mass spectrometry (HPLC-ESI-MS) method for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat tissues was established. Using this analytical method we evaluated whether acupuncture had a synergistic effect on the tissue distribution of schisandra lignans. Results Tissue concentrations of the three lignans in the group receiving acupuncture were significantly higher than those in the schisandra only group, suggesting that acupuncture may potently increase tissue concentrations of schisandra lignans. The highest concentrations of the three lignans occurred in the liver compared with other tissues, and tissue concentrations in the heart, spleen, lungs and kidneys were increased by 315%, 203%, 250% and 224%, respectively. In addition, retention times of the lignans in tissues were prolonged for a relative long time. Conclusions Our date indicate that the combined use of acupuncture and Schisandra chinensis could produce a synergistic effect which could play a beneficial role on promoting the tissue distribution of lignans. This has supported our initial hypothesis. The HPLC-MS method showed good sensitivity in quantifying the three schisandra lignans in different tissues.

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Nuclear receptors in disease: the oestrogen receptors

Essays in Biochemistry ◽

10.1042/bse0400157 ◽

2004 ◽

Vol 40 ◽

pp. 157-167 ◽

Cited By ~ 18

Author(s):

Maria Nilsson ◽

Karin Dahlman-Wright ◽

Jan-Åke Gustafsson

Keyword(s):

Nuclear Receptors ◽

Target Genes ◽

Receptor Subtype ◽

Target Tissue ◽

Oestrogen Receptors ◽

Nucleotide Polymorphisms ◽

Cell Type ◽

Single Nucleotide ◽

Beneficial Effects ◽

The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

Acta Endocrinologica ◽

10.1530/acta.0.068s279 ◽

1971 ◽

Vol 68 (1_Suppl) ◽

pp. S279-S294 ◽

Cited By ~ 12

Author(s):

Paul Robel

Keyword(s):

Steroid Hormone ◽

Physiological Activity ◽

Physiological State ◽

Target Cells ◽

Target Tissue ◽

Hormone Metabolism ◽

Metabolizing Enzymes ◽

Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

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EVALUATION OF TISSUE STEROID BINDING IN VITRO

Acta Endocrinologica ◽

10.1530/acta.0.068s223 ◽

1971 ◽

Vol 68 (1_Suppl) ◽

pp. S223-S246 ◽

Cited By ~ 2

Author(s):

C. R. Wira ◽

H. Rochefort ◽

E. E. Baulieu

Keyword(s):

Protein Binding ◽

Binding Sites ◽

Experimental System ◽

Specific Protein ◽

Coupling Mechanism ◽

Target Tissue ◽

Protein Binding Sites ◽

Definition Of ◽

Hormone Specificity

ABSTRACT The definition of a RECEPTOR* in terms of a receptive site, an executive site and a coupling mechanism, is followed by a general consideration of four binding criteria, which include hormone specificity, tissue specificity, high affinity and saturation, essential for distinguishing between specific and nonspecific binding. Experimental approaches are proposed for choosing an experimental system (either organized or soluble) and detecting the presence of protein binding sites. Techniques are then presented for evaluating the specific protein binding sites (receptors) in terms of the four criteria. This is followed by a brief consideration of how receptors may be located in cells and characterized when extracted. Finally various examples of oestrogen, androgen, progestagen, glucocorticoid and mineralocorticoid binding to their respective target tissues are presented, to illustrate how researchers have identified specific corticoid and mineralocorticoid binding in their respective target tissue receptors.

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