In Vivo Caries Models-Mechanisms for Caries Initiation and Arrestment

The effects of intra-oral mechanical forces on caries initiation, progression, and arrestment are evaluated by examination of different in vivo caries models. The models are grouped in four categories: (1) a population study, (2) short-term clinical trials, (3) clinical experiments, and (4) controlled clinical observations. Taken together, these in vivo studies convincingly demonstrate that partial or total elimination of the intra-oral mechanical forces operating during mastication or toothbrushing leads to evolution of cariogenic plaque, resulting in localized carious enamel dissolution. In addition, they show that re-exposure to the partly or totally eliminated mechanical forces not only arrests further lesion progression, but also results in partial lesion regression. The data from in vivo caries studies also show that the clinical and structural changes associated with lesion arrestment or partial regression are not related to any salivary repair mechanism, but are solely the result of mechanical removal of the cariogenic biomass which is physically interrelated with the eroded surface of the active, dull-whitish enamel lesion. No indications of superficial mineral deposition or "blocking" of the external intercrystalline spaces are seen in the surface layer of lesions arrested in vivo. For this reason, the conventional usage of the terminology 'remineralization' is considered absolutely misleading when used to describe the mechanisms responsible for the arrest of lesion progression in vivo.

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Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd7020021 ◽

2020 ◽

Vol 7 (2) ◽

pp. 21 ◽

Cited By ~ 1

Author(s):

Tyler L. Stevens ◽

Michael J. Wallace ◽

Mona El Refaey ◽

Jason D. Roberts ◽

Sara N. Koenig ◽

...

Keyword(s):

Structural Changes ◽

Mendelian Inheritance ◽

In Vivo Studies ◽

Arrhythmogenic Cardiomyopathy ◽

New Therapeutic Approaches ◽

Increased Risk ◽

Fatty Replacement ◽

Mechanistic Basis

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, and exercise has been documented to accelerate its progression. Although the genetic culprits are not exclusively limited to the intercalated disc, the majority of ACM-linked variants reside within desmosomal genes and are transmitted via Mendelian inheritance patterns; however, penetrance is highly variable. Its natural history features an initial “concealed phase” that results in patients being vulnerable to malignant arrhythmias prior to the onset of structural changes. Lack of effective therapies that target its pathophysiology renders management of patients challenging due to its progressive nature, and has highlighted a critical need to improve our understanding of its underlying mechanistic basis. In vitro and in vivo studies have begun to unravel the molecular consequences associated with disease causing variants, including altered Wnt/β-catenin signaling. Characterization of ACM mouse models has facilitated the evaluation of new therapeutic approaches. Improved molecular insight into the condition promises to usher in novel forms of therapy that will lead to improved care at the clinical bedside.

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CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies

Clinical Oral Investigations ◽

10.1007/s00784-020-03244-1 ◽

2020 ◽

Vol 24 (10) ◽

pp. 3661-3670 ◽

Cited By ~ 4

Author(s):

Birgit Rath-Deschner ◽

Svenja Memmert ◽

Anna Damanaki ◽

Marjan Nokhbehsaim ◽

Sigrun Eick ◽

...

Keyword(s):

Tooth Movement ◽

Orthodontic Tooth Movement ◽

In Vivo Studies ◽

Mechanical Forces ◽

Rt Pcr ◽

Mechanical Signals ◽

Periodontal Infection ◽

Experimental Periodontitis

Abstract Objectives This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals. Materials and methods The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA. Results Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level. Conclusions This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines. Clinical relevance Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.

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The ligand specificity of the G-protein-coupled receptor GPR34

Biochemical Journal ◽

10.1042/bj20112090 ◽

2012 ◽

Vol 443 (3) ◽

pp. 841-850 ◽

Cited By ~ 20

Author(s):

Lars Ritscher ◽

Eva Engemaier ◽

Claudia Stäubert ◽

Ines Liebscher ◽

Philipp Schmidt ◽

...

Keyword(s):

Structural Changes ◽

Transmembrane Helix ◽

In Vivo Studies ◽

Ligand Specificity ◽

Functional Specification ◽

Agonistic Activity ◽

Human Orthologue ◽

Lipid Compounds

Lyso-PS (lyso-phosphatidylserine) has been shown to activate the Gi/o-protein-coupled receptor GPR34. Since in vitro and in vivo studies provided controversial results in assigning lyso-PS as the endogenous agonist for GPR34, we investigated the evolutionary conservation of agonist specificity in more detail. Except for some fish GPR34 subtypes, lyso-PS has no or very weak agonistic activity at most vertebrate GPR34 orthologues investigated. Using chimaeras we identified single positions in the second extracellular loop and the transmembrane helix 5 of carp subtype 2a that, if transferred to the human orthologue, enabled lyso-PS to activate the human GPR34. Significant improvement of agonist efficacy by changing only a few positions strongly argues against the hypothesis that nature optimized GPR34 as the receptor for lyso-PS. Phylogenetic analysis revealed several positions in some fish GPR34 orthologues which are under positive selection. These structural changes may indicate functional specification of these orthologues which can explain the species- and subtype-specific pharmacology of lyso-PS. Furthermore, we identified aminoethyl-carbamoyl ATP as an antagonist of carp GPR34, indicating ligand promiscuity with non-lipid compounds. The results of the present study suggest that lyso-PS has only a random agonistic activity at some GPR34 orthologues and the search for the endogenous agonist should consider additional chemical entities.

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Antimalarial potential of quinones isolated from plants: an integrative review

Research Society and Development ◽

10.33448/rsd-v10i2.12507 ◽

2021 ◽

Vol 10 (2) ◽

pp. e38210212507

Author(s):

Antonio Rafael Quadros Gomes ◽

Heliton Patrick Cordovil Brígido ◽

Valdicley Vieira Vale ◽

Juliana Correa-Barbosa ◽

Sandro Percário ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Natural Products ◽

Plasmodium Berghei ◽

Structural Changes ◽

In Vivo Studies ◽

Inclusion Criteria ◽

Antimalarial Treatment ◽

Exclusion Criteria ◽

Therapeutic Alternatives

Antimalarial treatment is often associated with the resistance developed by Plasmodium which generate ineffective drug treatment. Based on this, the search for therapeutic alternatives is necessary and urgent. This review intends to assess the antimalarial potential of quinones isolated from plants. The search for scientific articles was carried out on the CAPES Journal Portal (PPC), Virtual Health Library (VHL), PUBMED, NCBI and SCIELO, using the following descriptors: quinones and antimalarials. Inclusion criteria were adopted based on studies about quinones isolated from plants and tested against Plasmodium falciparum and Plasmodium berghei. The exclusion criteria were based mainly on articles that tested extracts, fractions and synthesis of quinones obtained from plants and other natural products. A total of 1344 publications were collected for screening (PPC = 5, VHL = 248, PUBMED = 525, NCBI = 462 and SCIELO = 94). From this total, 1280 articles were excluded, with only 64 articles selected for full reading. All benzoquinones were active against P. falciparum. Naphthoquinones were active, inactive and moderately active against the P. falciparum e P berghei. Anthraquinones and anthrones were active and moderately active against P. falciparum. The naphthoquinone 2-acetylnaphtho- [2,3b] -furan-4,9-dione was the most active of all the molecules tested against Plasmodium. Whereas lapachol was the most studied naphthoquinone and structural changes do not seem to contribute to the activity. In summary, quinones are promising as antimalarials, however, need in vivo studies.

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Limited capacity for renal vasodilatation in anesthetized diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.4.h845 ◽

1987 ◽

Vol 253 (4) ◽

pp. H845-H855

Author(s):

H. Ha ◽

E. W. Dunham

Keyword(s):

Structural Changes ◽

Control Period ◽

Systemic Arterial Pressure ◽

Diabetic Rats ◽

In Vivo Studies ◽

Renal Vasculature ◽

Humoral Factors ◽

Renal Vasoconstriction ◽

Renal Vascular

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled streptozotocin (STZ)-induced diabetes is attributable to diabetes-induced structural changes in the renal vasculature. Vehicle-treated control rats (CR) and rats that were injected with STZ (STZR) after pretreatment with 3-O-methylglucose (3-OMG), an agent that prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (ml.min-1.g kidney wt-1, electromagnetic flow probe), systemic arterial pressure (BP, mmHg), and renal vascular resistance (RVR, BP/RBF) in pentobarbital-anesthetized rats during a control period were 5.4 +/- 0.3 (P less than 0.01 vs. CR), 116 +/- 3, and 21.9 +/- 1.0 (P less than 0.01 vs. CR) in STZR (n = 12) and 8.2 +/- 0.4, 121 +/- 2, and 15.3 +/- 1.0 in CR (n = 11), respectively. Basal values of RBF, BP, and RVR in 3-OMG-pretreated STZR were identical to CR. The relative capacity of STZR and CR kidneys for vasodilatation in situ in response to intrarenal arterial infusions of acetylcholine (ACh) and bradykinin (BK) and systemically administered sodium nitroprusside (NP) was evaluated. The capacity of STZR to exhibit active renal vasodilatation in response to intrarenal arterial ACh and BK was significantly less than that of CR (P less than 0.01). The minimum level to which RVR was suppressed after 50 micrograms NP/kg iv was higher in STZR than in either CR or 3-OMG-pretreated STZR (14.8 +/- 1.5 vs. 9.0 +/- 0.7 and 9.3 +/- 1.5 mmHg.ml-1.min.g kidney wt, respectively; P less than 0.05). This dose of NP exerted effective functional antagonism of renal vasoconstriction induced by exogenous norepinephrine and angiotensin II. These in vivo studies suggest that the elevated RVR in STZR might be attributable in part to structural changes in the renal vasculature that are associated with the diabetic state and limit the capacity for renal vasodilatation. However, there was no difference in pressure-flow relationships between the two groups in maximally dilated isolated kidneys perfused with Krebs buffer containing 5% albumin, and the RBF deficit in STZR kidneys was corrected by perfusion with blood from CR. Thus the decreased RBF exhibited by STRZ in vivo cannot be attributed solely to renal vascular structural changes associated with diabetes. These findings suggest that undefined humoral factors or abnormal interaction of formed blood elements with vessel walls may account for elevated RVR in STZR.

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Bronchoconstriction: a potential missing link in airway remodelling

Open Biology ◽

10.1098/rsob.200254 ◽

2020 ◽

Vol 10 (12) ◽

pp. 200254

Author(s):

Michael J. O'Sullivan ◽

Thien-Khoi N. Phung ◽

Jin-Ah Park

Keyword(s):

Deleterious Effect ◽

Structural Changes ◽

Ex Vivo ◽

Airway Remodelling ◽

Mechanical Forces ◽

Airway Wall ◽

Comprehensive Understanding ◽

Missing Link

In asthma, progressive structural changes of the airway wall are collectively termed airway remodelling. Despite its deleterious effect on lung function, airway remodelling is incompletely understood. As one of the important causes leading to airway remodelling, here we discuss the significance of mechanical forces that are produced in the narrowed airway during asthma exacerbation, as a driving force of airway remodelling. We cover in vitro , ex vivo and in vivo work in this field, and discuss up-to-date literature supporting the idea that bronchoconstriction may be the missing link in a comprehensive understanding of airway remodelling in asthma.

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Fine Structural Changes in the Microvasculature of the Mouse Pinna: Aging and Radiation Injury

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050287 ◽

1974 ◽

Vol 32 ◽

pp. 54-55

Author(s):

S. Phyllis Steamer ◽

Rosemarie L. Devine

Keyword(s):

Structural Changes ◽

Radiation Treatment ◽

Arterial Stenosis ◽

Ultrastructural Changes ◽

Vascular Effects ◽

Microvascular Changes ◽

Surrounding Connective Tissue ◽

Fission Neutrons ◽

Total Body

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.

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