scholarly journals Phlorizin Pretreatment Reduces Acute Renal Toxicity in a Mouse Model for Diabetic Nephropathy

2013 ◽  
Vol 288 (38) ◽  
pp. 27200-27207 ◽  
Author(s):  
Bas Brouwers ◽  
Vincent P. E. G. Pruniau ◽  
Elisa J. G. Cauwelier ◽  
Frans Schuit ◽  
Evelyne Lerut ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Gastric Emptying ◽  
Side Effects ◽  
Delayed Gastric Emptying ◽  
Renal Toxicity ◽  
High Dose ◽  
Cell Toxicity ◽  
Β Cell ◽  
Kidney Toxicity ◽  
Efficient Regime

Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

scholarly journals Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function

2014 ◽  
Vol 307 (6) ◽  
pp. E494-E502 ◽  
Author(s):  
Ling Hinshaw ◽  
Michele Schiavon ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
Rita Basu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Insulin Sensitivity ◽  
Delayed Gastric Emptying ◽  
Cell Function ◽  
Postprandial Glucose ◽  
Β Cell ◽  
C Peptide ◽  
Β Cell Function

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

At a high dose even partially degraded beta-glucan with decreased solubility significantly reduced the glycaemic response to bread

2019 ◽  
Vol 10 (3) ◽  
pp. 1529-1539 ◽  
Author(s):  
Anne Rieder ◽  
Svein H. Knutsen ◽  
Aida Sainz Fernandez ◽  
Simon Ballance
Keyword(s):  
Gastric Emptying ◽  
Delayed Gastric Emptying ◽  
Starch Digestibility ◽  
High Dose ◽  
Mucus Layer ◽  
Glycaemic Response ◽  
Beta Glucan ◽  
Explanatory Factors ◽  
High Beta

Breads with high beta-glucan contents reduce glycaemic responses. Dilution of nutrients, delayed gastric emptying or mucus-layer interaction are possible explanatory factors, but not bulk viscosity or in vitro starch digestibility.

Quality-by-Design Enabled Chitosan Nanoparticles for Antitubercular Therapy: Formulation, Statistical Optimization, and In vitro Characterization

2020 ◽  
Vol 15 ◽  
Author(s):  
Manasi M. Chogale ◽  
Sujay S. Gaikwad ◽  
Savita P. Kulkarni ◽  
Vandana B. Patravale
Keyword(s):  
Side Effects ◽  
Treatment Regimen ◽  
Research Work ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Antitubercular Therapy ◽  
Prolonged Treatment ◽  
High Dose ◽  
Average Size

Background: Tuberculosis (TB) continues to be among the leading causes for high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated sideeffects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drugexcipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Qualityby-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.

scholarly journals TNF-Alpha Inhibitors for Chronic Urticaria: Experience in 20 Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Freja Lærke Sand ◽  
Simon Francis Thomsen
Keyword(s):  
Side Effects ◽  
Chronic Urticaria ◽  
Treatment Options ◽  
Significant Proportion ◽  
Response Duration ◽  
Immunosuppressive Drugs ◽  
Tnf Alpha ◽  
High Dose ◽  
Duration Of Treatment ◽  
Durable Response

Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria. Twelve (60%) patients obtained complete or almost complete resolution of urticaria after onset of therapy with either adalimumab or etanercept. Further three patients (15%) experienced partial response. Duration of treatment ranged between 2 and 39 months. Those responding completely or almost completely had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.

scholarly journals Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice

2021 ◽  
Vol 137 ◽  
pp. 111370
Author(s):  
Chethan Sampath ◽  
Derek Wilus ◽  
Mohammad Tabatabai ◽  
Michael L. Freeman ◽  
Pandu R. Gangula
Keyword(s):  
Gastric Emptying ◽  
High Fat Diet ◽  
Delayed Gastric Emptying ◽  
High Fat ◽  
Female Mice

Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab

2021 ◽  
pp. 112067212199104
Author(s):  
Catherine J Hwang ◽  
Erin E Nichols ◽  
Brian H Chon ◽  
Julian D Perry
Keyword(s):  
Side Effects ◽  
Optic Neuropathy ◽  
Surgical Decompression ◽  
Thyroid Eye Disease ◽  
Eye Disease ◽  
High Dose ◽  
Compressive Optic Neuropathy ◽  
Traditional Management ◽  
Immune Mediated ◽  
Orbital Radiation

Thyroid eye disease is an auto-immune mediated orbitopathy which can cause dysthyroid compressive optic neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA-approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically utilizing teprotumumab.

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