scholarly journals Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Xi Sun ◽  
Qi Guo ◽  
Wenhua Wei ◽  
Stephen Robertson ◽  
Ying Yuan ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Osteoporotic Fracture ◽  
Osteoporotic Fractures ◽  
Chemical Modifications ◽  
Treatment Of Osteoporosis ◽  
Gene Therapies ◽  
Novel Approaches ◽  
Biological Performance

Emerging evidence demonstrates that microRNAs, as important endogenous posttranscriptional regulators, are essential for bone remodeling and regeneration. Undoubtedly, microRNA-based gene therapies show great potential to become novel approaches against bone-related diseases, including osteoporosis and associated fractures. The major obstacles for continued advancement of microRNA-based therapies in clinical application include their poorin vivostability, nonspecific biodistribution, and unwanted side effects. Appropriate chemical modifications and delivery vectors, which improve the biological performance and potency of microRNA-based drugs, hold the key to translating miRNA technologies into clinical practice. Thus, this review summarizes the current attempts and existing deficiencies of chemical modifications and delivery systems applied in microRNA-based therapies for osteoporosis and osteoporotic fractures to inform further explorations.

The new target therapy to prevent weight gain associated to atypical antipsychotics: PKCβ

2017 ◽  
Vol 41 (S1) ◽  
pp. S370-S371
Author(s):  
C. Pavan ◽  
A. Rimessi ◽  
B. Zavan ◽  
V. Vindigni ◽  
P. Pinton
Keyword(s):  
Clinical Practice ◽  
Weight Gain ◽  
Side Effects ◽  
Cell Biology ◽  
Target Therapy ◽  
Premature Death ◽  
Preclinical Model ◽  
Psychomotor Tests

Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Clozapine is the most effective medication for treatment-resistant schizophrenia, in controlling aggression and suicidal behavior in psychosis. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, weight gain and metabolic side effects are well known in clinical practice exposing the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence. The mechanisms underlying this pharmacologically activated disorders are still controversial. Based on our in vitro results, we have characterized in vivo the effects of the selective PKCβ inhibitor, Ruboxistaurin (LY-333531) on a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry and psychomotor tests have been performed on wild type and PKCβ (-/-) mutant mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibitor on the neuroleptic effect of clozapine. Lastly, we also shed light on a novel aspect of the mechanism underlying of clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promote the inhibition of the lipid droplet-selective autophagy process, opening the way to new therapeutic intervention approach.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Nutritional status and nutritional management in children with cancer

2015 ◽  
Vol 100 (12) ◽  
pp. 1169-1172 ◽  
Author(s):  
Edward P T Gaynor ◽  
Peter B Sullivan
Keyword(s):  
Side Effects ◽  
Nutritional Status ◽  
Risk Stratification ◽  
Treatment Strategies ◽  
Nutritional Risk ◽  
Nutritional Management ◽  
Children With Cancer ◽  
Childhood Malignancy ◽  
Novel Approaches

Malnutrition is often seen at the point of diagnosis in childhood malignancy or may develop during the course of treatment. Strategies for optimal diagnosis and management of nutritional problems in children with cancer are limited in the published literature. Identification of children who may be malnourished or at nutritional risk can be achieved through improved approaches for risk stratification and classification. Once recognised, various strategies have been demonstrated to reduce malnutrition, minimise side effects of treatment and improve survival. Novel approaches in vivo and adult oncology populations provide future avenues for investigation.

Novel Ways to Use Exposure for Eating Disorders

2019 ◽  
pp. 165-172
Author(s):  
Carolyn Black Becker ◽  
Nicholas R. Farrell ◽  
Glenn Waller
Keyword(s):  
Eating Disorders ◽  
Eating Disorder ◽  
Clinical Practice ◽  
Magical Thinking ◽  
Interoceptive Exposure ◽  
Imaginal Exposure ◽  
Eating Disorder Treatment ◽  
Disorder Treatment ◽  
Novel Approaches

Three relatively novel approaches to the use of exposure for eating disorders are considered. Each is relatively experimental in treating eating disorders but is well established in treating anxiety-based disorders. Interoceptive exposure can be used to treat distress over bodily cues (e.g., fullness). Imaginal exposure can be used to elevate and treat anxiety as a prelude to in vivo exposure, although it should be used only when necessary. Finally, exposure can be used to address “magical thinking,” such as thought–shape fusion. These methods show promise with eating disorder treatment but are in the early stages of conceptualization and development. Their use should be treated as experimental at present, and clinicians should be alert to their impact in clinical practice.

scholarly journals The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2682 ◽  
Author(s):  
Miguel Muñoz ◽  
Rafael Coveñas
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Cancer Patients ◽  
Antitumor Agent ◽  
Antitumor Action ◽  
Tumor Mass ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

scholarly journals The Risk of Osteoporosis and Osteoporotic Fracture Following the Use of Irritable Bowel Syndrome Medical Treatment: An Analysis Using the OMOP CDM Database

2021 ◽  
Vol 10 (9) ◽  
pp. 2044
Author(s):  
Gyu Lee Kim ◽  
Yu Hyeon Yi ◽  
Hye Rim Hwang ◽  
Jinmi Kim ◽  
Youngmin Park ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Osteoporotic Fracture ◽  
Data Model ◽  
Large Scale ◽  
Osteoporotic Fractures ◽  
Common Data Model ◽  
Medical Outcomes ◽  
Treatment Of Osteoporosis ◽  
Increased Risk ◽  
Irritable Bowel

Patients with irritable bowel syndrome (IBS) are at increased risk of osteoporosis and osteoporotic fracture. This study investigated whether IBS medication attenuated the rate of osteoporosis and osteoporotic fracture risk. We conducted a retrospective large-scale multicenter study across eight hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporosis, whereas secondary outcomes were osteoporotic fractures. After 1:4 matching, 24,723 IBS patients, 78,318 non-IBS patients, 427,640 non-IBS patients with IBS medication, and 827,954 non-IBS patients without IBS medication were selected. The risk of osteoporosis was significantly increased in the IBS group compared to the non-IBS group (hazard ratio (HR) 1.33; confidence interval (CI) 1.17~1.51). Even in patients who were not diagnosed with IBS, the risk of osteoporosis was significantly increased in those with IBS medication compared to those without (HR 1.77, CI 1.62~1.93). The risk of osteoporotic fracture was significantly increased in the IBS medication group (HR 1.69, CI 1.55~1.84). Patients exposed to IBS treatment even without IBS diagnosis were at increased risk of osteoporosis and osteoporotic fracture. Early diagnosis and treatment of osteoporosis should be considered in patients who have received medication for IBS symptoms.

New approaches for the local prevention of osteoporotic fractures

2012 ◽  
Vol 1376 ◽  
Author(s):  
P. Janvier ◽  
V. Schnitzler ◽  
J.-M. Bouler ◽  
O. Gauthier ◽  
C. Despas ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Chemical Exchange ◽  
Local Treatment ◽  
Osteoporotic Fractures ◽  
Treatment Of Osteoporosis ◽  
Continuous Flow Condition ◽  
Setting Process ◽  
Osteoclastic Resorption ◽  
Main Component

ABSTRACTCombining Bisphophonates (BPs) and Calcium Phosphate Cement (CPC) to form a new medical device for the local treatment of Osteoporosis is a promising challenge. Our formulation was optimized from an apatitic-type CPC and we have shown that the best solution consists in introducing the bisphosphonate (Alendronate) in the calcium deficient apatite (CDA), a solid component of the cement, through a chemical exchange reaction. The cement obtained was characterized by 31P NMR and high frequency impedance for monitoring the CPC setting. The presence of Alendronate in the cement was also demonstrated by 31P NMR which has been also used to characterize the chemical transformation of α-TCP (main component of the apatitic cement) during the setting process. BP absorption/desorption experiments have been realized on cement blocks, under continuous flow condition, to model the release profile of the Alendronate. In vivo experiments showed promising results in terms of resorbability of the Alendronate–loaded cement while promoting new bone formation. The same methodology is considered to introduce gallium, a potential inhibitor of osteoclastic resorption, in a CPC formulation. First experiments have shown that gallium can be incorporated in calcium phosphate ceramics (i.e. β-TCP) where gallium is part of the network.

scholarly journals Selective Carboxylesterase Inhibitors for Improving Efficacy, Safety and Rational use of Ester-Containing Drugs

2018 ◽  
Vol 1 (3) ◽  
pp. e00026 ◽  
Author(s):  
N.P. Boltneva ◽  
G.F. Makhaeva ◽  
E.V. Shchegol’kov ◽  
Ya.V. Burgart ◽  
V.I. Saloutin
Keyword(s):  
Clinical Practice ◽  
Drug Therapy ◽  
Side Effects ◽  
Medicinal Chemistry ◽  
The Body ◽  
Toxic Effects ◽  
Selective Inhibitors ◽  
Rational Use ◽  
Key Enzyme

In clinical practice, a large number of prodrugs and active drugs containing an ester, carbamate or amide moiety are used. Carboxylesterase (CaE, EC 3.1.1.1) is the key enzyme of hydrolytic metabolism of such drugs in the body, it largely determines their pharmacokinetics, bioavailability, efficacy and possible toxic effects. Using CaE selective inhibitors as components of combined drug therapy it is possible us to regulate the rate of hydrolytic transformation of ester-containing drugs and opens the possibility of their rational use. The development of effective and selective CaE inhibitors suitable for in vivo application is a new promising approach in medicinal chemistry and pharmacology that allows to improve the efficacy, bioavailability and reduce the side effects of ester-containing drugs.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

1984 ◽  
Vol 51 (02) ◽  
pp. 248-253 ◽  
Author(s):  
R J Dupe ◽  
P D English ◽  
R A G Smith ◽  
J Green
Keyword(s):  
Pulmonary Embolism ◽  
Side Effects ◽  
Venous Thrombosis ◽  
Active Site ◽  
Acute Pulmonary Embolism ◽  
Quantitative Model ◽  
Beagle Dog ◽  
Thrombosis Model ◽  
Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

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