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- Bahadoran, Z, et al.
(författare)
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Different Pharmacokinetic Responses to an Acute Dose of Inorganic Nitrate in Patients with Type 2 Diabetes
- 2021
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Ingår i: Endocrine, metabolic & immune disorders drug targets. - : Bentham Science Publishers Ltd.. - 2212-3873 .- 1871-5303. ; 21:5, s. 878-886
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3was also assessed.Methods:Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO3concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured.Results:Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 μmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 μmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal.Conclusion:T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3supplementation.
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- Bekris, L M, et al.
(författare)
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Targeting type 1 diabetes before and at the clinical onset of disease.
- 2006
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Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 2212-3873 .- 1871-5303. ; 6:1, s. 103-124
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune type 1 diabetes is strongly associated with a number of immune abnormalities that manifest themselves before and at the time of clinical diagnosis. The clinical onset is associated with a major loss of the pancreatic islet beta cells. Insulin treatment is the only treatment option since numerous trials with agents that suppress or modulate immune function have failed to preserve beta cell function long term. Recent studies suggest that it is possible to predict clinical onset of diabetes by combining genetic with autoantibody testing. In this review we will summarize current and future drug targets for subjects at risk for type 1 diabetes as well as for subjects with recent onset disease. We will also discuss the possible importance of initiating as well as contributing factors such as reactive oxygen species and modified autoantigens. It is speculated that drug targets of factors important to disease pathogenesis may provide safe and effective adductive treatment to preserve beta cell function in autoantibody positive subjects who are at maximum risk for disease.
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- Grimaldi, Franco, et al.
(författare)
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Assessment of Response to Treatment and Follow-Up in Gastroenteropancreatic Neuroendocrine Neoplasms
- 2018
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Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - : Bentham Science. - 1871-5303 .- 2212-3873. ; 18:5, s. 419-449
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Tidskriftsartikel (refereegranskat)abstract
- Well-established criteria for evaluating the response to treatment and the appropriate follow-up of individual patients are critical in clinical oncology. The current evidence-based data on these issues in terms of the management of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are unfortunately limited. This document by the Italian Association of Clinical Endocrinologists (AME) on the criteria for the follow-up of GEP-NEN patients is aimed at providing comprehensive recommendations for everyday clinical practice based on both the best available evidence and the combined opinion of an interdisciplinary panel of experts. The initial risk stratification of patients with NENs should be performed according to the grading, staging and functional status of the neoplasm and the presence of an inherited syndrome. The evaluation of response to the initial treatment, and to the subsequent therapies for disease progression or recurrence, should be based on a cost-effective, risk-effective and timely use of the appropriate diagnostic resources. A multidisciplinary evaluation of the response to the treatment is strongly recommended and, at every step in the follow-up, it is mandatory to assess the disease state and the patient performance status, comorbidities, and recent clinical evolution. Local expertise, available technical resources and the patient preferences should always be evaluated while planning the individual clinical management of GEP-NENs.
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- Leanderson, Tomas, et al.
(författare)
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S100A9 as a pharmacological target molecule in inflammation and cancer.
- 2015
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Ingår i: Endocrine, Metabolic & Immune Disorders - Drug Targets. - 2212-3873. ; 15:2, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- Upon tissue injury and infection both stressed and dying cells can release proteins that normally reside inside the cells. Some of the released proteins become ligands of various cell surface receptors expressed by local cells and such proteins are denoted damage associated molecular patterns (DAMPs). Binding of some DAMPs to certain cell surface receptors induces signals emanating in the production of pro-inflammatory cytokines, ultimately leading to an inflammatory response. Our laboratory is interested in the S100A9 protein, a bona fide DAMP protein. This protein normally resides inside monocytes and neutrophils and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9 heterodimer is released in large amounts during several types of inflammatory disease and is currently used clinically as a biomarker in some diseases. The fact that several different pro-inflammatory functions have been ascribed to this protein makes it a potential target for the development of small molecule inhibitors. We have developed several such inhibitors, some of which are already in phase III clinical development. This review describes our efforts to investigate the biological functions of the S100A9 protein as well as our ongoing efforts of developing second-generation, more specific, small molecule inhibitors of its pro-inflammatory functions.
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