scholarly journals Periodontitis in Patients with Diabetes— A Complication that Impacts on Metabolic Control

2012 ◽  
Vol 08 (01) ◽  
pp. 35 ◽  
Author(s):  
Corneliu Sima ◽  
Michael Glogauer ◽  
◽  
Keyword(s):  
Animal Studies ◽  
Randomized Clinical Trials ◽  
Periodontal Diseases ◽  
Diabetic Patients ◽  
Low Grade ◽  
Established Risk Factor ◽  
Biological Phenomena ◽  
Bidirectional Relationship ◽  
Patients With Diabetes

Diabetes and periodontal diseases (PDs) exhibit a bidirectional relationship centered on an enhanced inflammatory response that manifests both locally and systemically. Diabetes is an established risk factor for PD, whereas the treatment of the latter has been shown to improve glycemic control in diabetic patients. Although compelling evidence fromin vitroand animal studies supports a plausible biological explanation for the relationship between the two conditions centered on systemic low-grade inflammation, the limited number of comparable large randomized clinical trials is reflected in the limited specific guidelines offered by the international organizations for diabetes and periodontitis regarding the management of the two diseases in an individual. Further understanding of the biological phenomena underlying PDs and diabetes is critical for individual therapeutic approaches to patients with both conditions by endocrinologists and periodontists.

scholarly journals Diabetes mellitus and periodontal diseases: A two way relationship

2021 ◽  
Vol 6 (2) ◽  
pp. 43-56
Author(s):  
Gowhar Nazir ◽  
◽  
Josee Amin ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Periodontal Disease ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Systemic Effect ◽  
Diabetic Patients ◽  
Periodontal Infection ◽  
Bidirectional Relationship ◽  
Patients With Diabetes ◽  
Global Health Care

Diabetes mellitus and periodontits are both highly prevalent chronic inflammatory diseases. Both diseases share the same risk factors and are a significant global health care burden adversely affecting the quality of life. Evidence from various studies have demonstrated that diabetes is a major risk factor for periodontal disease and is associated with increased incidence, prevalence and severity of periodontal disease. Hyperglycemia associated with diabetes mellitus results in an increased host immunoinflammatory response which adversely affects the periodontal health. Conversely, periodontits is associated with poor metabolic control in patients with diabetes and increased development of diabetic complications suggesting a bidirectional relationship between the two diseases. Periodontal infection via bacteremia exerts a wide systemic effect by contributing to chronic systemic inflammatory burden worsening diabetic state by increasing insulin resistance. Moreover, studies have demonstrated an improvement in glycemic control following periodontal therapy in prediabetic and diabetic patients with periodontitis.

scholarly journals Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted?

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Bernardino Clavo ◽  
Norberto Santana-Rodríguez ◽  
Pedro Llontop ◽  
Dominga Gutiérrez ◽  
Gerardo Suárez ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Immune Modulation ◽  
Animal Studies ◽  
Potential Role ◽  
Randomized Clinical Trials ◽  
Tumor Hypoxia ◽  
Tumor Resection ◽  
Ozone Therapy

Introduction. This article provides an overview of the potential use of ozone as an adjuvant during cancer treatment.Methods. We summarize the findings of the most relevant publications focused on this goal, and we include our related clinical experience.Results. Over several decades, prestigious journals have publishedin vitrostudies on the capacity of ozone to induce direct damage on tumor cells and, as well, to enhance the effects of radiotherapy and chemotherapy. Indirect effects have been demonstrated in animal models: immune modulation by ozone alone and sensitizing effect of radiotherapy by concurrent ozone administration. The effects of ozone in modifying hemoglobin dissociation curve, 2,3-diphosphoglycerate levels, locoregional blood flow, and tumor hypoxia provide additional support for potential beneficial effects during cancer treatment. Unfortunately, only a few clinical studies are available. Finally, we describe some works and our experience supporting the potential role of local ozone therapy in treating delayed healing after tumor resection, to avoid delays in commencing radiotherapy and chemotherapy.Conclusions.In vitroand animal studies, as well as isolated clinical reports, suggest the potential role of ozone as an adjuvant during radiotherapy and/or chemotherapy. However, further research, such as randomized clinical trials, is required to demonstrate its potential usefulness as an adjuvant therapeutic tool.

scholarly journals The Functionality of Endothelial-Colony-Forming Cells from Patients with Diabetes Mellitus

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1731
Author(s):  
Caomhán J. Lyons ◽  
Timothy O'Brien
Keyword(s):  
Diabetes Mellitus ◽  
Cell Therapy ◽  
Diabetic Patients ◽  
Angiogenic Potential ◽  
Endothelial Colony Forming Cells ◽  
Allogeneic Cell Therapy ◽  
Patients With Diabetes ◽  
Pre Treatment

Endothelial-colony-forming cells (ECFCs) are a population of progenitor cells which have demonstrated promising angiogenic potential both in vitro and in vivo. However, ECFCs from diabetic patients have been shown to be dysfunctional compared to ECFCs from healthy donors. Diabetes mellitus itself presents with many vascular co-morbidities and it has been hypothesized that ECFCs may be a potential cell therapy option to promote revascularisation in these disorders. While an allogeneic cell therapy approach would offer the potential of an ‘off the shelf’ therapeutic product, to date little research has been carried out on umbilical cord-ECFCs in diabetic models. Alternatively, autologous cell therapy using peripheral blood-ECFCs allows the development of a personalised therapeutic approach to medicine; however, autologous diabetic ECFCs are dysfunctional and need to be repaired so they can effectively treat diabetic co-morbidities. Many different groups have modified autologous diabetic ECFCs to improve their function using a variety of methods including pre-treatment with different factors or with genetic modification. While the in vitro and in vivo data from the literature is promising, no ECFC therapy has proceeded to clinical trials to date, indicating that more research is needed for a potential ECFC therapy in the future to treat diabetic complications.

scholarly journals Recent Advances in the Use of Metformin: Can Treating Diabetes Prevent Breast Cancer?

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Diana Hatoum ◽  
Eileen M. McGowan
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Clinical Studies ◽  
Clinical Trial Data ◽  
The Elderly ◽  
Diabetic Patients ◽  
Positive Trend ◽  
Patients With Diabetes ◽  
Meta Analyses

There is substantial epidemiological evidence pointing to an increased incidence of breast cancer and morbidity in obese, prediabetic, and diabetic patients.In vitrostudies strongly support metformin, a diabetic medication, in breast cancer therapy. Although metformin has been heralded as an exciting new breast cancer treatment, the principal consideration is whether metformin can be used as a generic treatment for all breast cancer types. Importantly, will metformin be useful as an inexpensive therapy for patients with comorbidity of diabetes and breast cancer? In general, meta-analyses of clinical trial data from retrospective studies in which metformin treatment has been used for patients with diabetes and breast cancer have a positive trend; nevertheless, the supporting clinical data outcomes remain inconclusive. The heterogeneity of breast cancer, confounded by comorbidity of disease in the elderly population, makes it difficult to determine the actual benefits of metformin therapy. Despite the questionable evidence available from observational clinical studies and meta-analyses, randomized phases I–III clinical trials are ongoing to test the efficacy of metformin for breast cancer. This special issue review will focus on recent research, highlightingin vitroresearch and retrospective observational clinical studies and current clinical trials on metformin action in breast cancer.

scholarly journals TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 42
Author(s):  
Simona Cataldi ◽  
Marianna Aprile ◽  
Daniela Melillo ◽  
Inès Mucel ◽  
Sophie Giorgetti-Peraldi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Precursor Cells ◽  
Dominant Negative ◽  
Inflammatory Factors ◽  
Diabetic Patients ◽  
Low Grade ◽  
Mesenchymal Precursor Cells ◽  
Inflammatory Macrophages ◽  
The Impact

Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα is identified herein as factor able to alter PPARG splicing—increasing PPARGΔ5/cPPARG ratio—through PI3K/Akt signaling and SRp40 splicing factor. In line with in vitro data, TNFA expression is higher in the SAT of obese (vs. lean) patients and positively correlates with PPARGΔ5 levels. In conclusion, our results indicate that inflammatory factors secreted by metabolically-activated macrophages are potent stimuli that modulate the expression and splicing of PPARG. The resulting imbalance between canonical and dominant negative isoforms may crucially contribute to impair PPARγ activity in hypertrophic AT, exacerbating the defective adipogenic capacity of precursor cells.

scholarly journals Primum non nocere – Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

2020 ◽  
Vol 54 ◽  
pp. 68 ◽  
Author(s):  
Claudia Biguetti ◽  
Mauro Toledo Marrelli ◽  
Marco Brotto
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Animal Studies ◽  
Prophylactic Treatment ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Vulnerable Groups ◽  
Drug Effectiveness ◽  
Risk Balance

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-CoV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. In this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-CoV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use. DESCRIPTORS: Coronavirus Infections. Chloroquine, toxicity. Hydroxychloroquine, toxicity. Contraindications, Drug.

scholarly journals L-cysteine Supplementation Increases Blood Levels of Hydrogen Sulfide and Nitrite, and Decreases Insulin Resistance and Vascular Inflammation in Zucker Diabetic Rats

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 405-405
Author(s):  
Sushil Jain
Keyword(s):  
Insulin Resistance ◽  
Hydrogen Sulfide ◽  
Animal Studies ◽  
Vascular Inflammation ◽  
Diabetic Animal ◽  
Diabetic Rats ◽  
Blood Levels ◽  
Diabetic Patients ◽  
Zdf Rats

Abstract Objectives Diabetic patients have lower blood levels of hydrogen sulfide (H2S). H2S has potent antioxidant, anti-inflammatory and anti-atherosclerotic effects in vitro and in animal studies. This study examined the hypothesis that supplementation with L-cysteine, an endogenous precursor of H2S increases blood levels of H2S and lowers insulin resistance and vascular inflammation biomarkers in type 2 diabetes using Zucker diabetic (ZDF) rats as a model. Methods Starting at age of 6 weeks, ZDF rats were supplemented orally, daily gavages for 8 weeks with saline-placebo (D, n = 8) or L-cysteine (LC, n = 12, 1 mg/kg BW) and fed a high calorie diet. 6 weeks age rats without any supplementation were considered baseline (BL) rats. Results Fasting blood levels of D rats showed lower H2S and elevated HGb, MCP-1 and insulin resistance when compared with baseline in which there was no onset of diabetes. LC supplementation significantly (P < 0.05) increased blood levels of H2S (37%), and NO2 (30%) and lowered levels of GHb (9%), MCP-1 (31%), TNF (31%) and HOMA insulin resistance (25%) compared with levels seen in saline supplemented D. The blood levels of GHb and IR showed a significant correlation (P < 0.05) with concentrations of H2S and nitrite in LC-supplemented ZDF rats. Conclusions This shows that L-cysteine supplementation can increase levels of H2S and NO2 in diabetic animal model, and needs to be validated as an adjuvant therapy for the reduction of vascular inflammation and insulin resistance in the diabetic patient population. Funding Sources This study was supported by the NCCIH.

Role of Chemically Modified Tetracyclines in the Management of Periodontal Diseases: A Review

Drug Research ◽  
2017 ◽  
Vol 67 (05) ◽  
pp. 258-265 ◽  
Author(s):  
Archit Ghangurde ◽  
Kiran Ganji ◽  
Manohar Bhongade ◽  
Bhumika Sehdev
Keyword(s):  
Animal Studies ◽  
Metabolic Diseases ◽  
Periodontal Diseases ◽  
Gelatinase Activity ◽  
Chemically Modified ◽  
Periodontal Breakdown ◽  
Osteoclast Function ◽  
Chemically Modified Tetracyclines

AbstractResearchers have found that Chemically Modified Tetracyclines (CMTs) act through multiple mechanisms, affecting several parameters of osteoclast function and consequently inhibit bone resorption by altering intracellular calcium concentration and interacting with the putative calcium receptor; decreasing ruffled border area; diminishing acid production; diminishing the secretion of lysosomal cysteine proteinases (cathepsins); inducing cell retraction by affecting podosomes; inhibiting osteoclast gelatinase activity; selectively inhibiting osteoclast ontogeny or development; and inducing apoptosis or programmed cell death of osteoclasts. Thus TCs/CMTs, as anti-resorptive drugs, may act similarly to bisphosphonates and primarily affect osteoclast function. Researchers have evaluated the influence of various chemically modified tetracyclines from CMT-1 to CMT-10 on collagenases and gelatinases through in vitro or animal studies and concluded that all the CMTs except CMT-5 inhibited periodontal breakdown through MMP inhibition in the following order of efficacy: CMT-8>CMT-1>CMT-3>CMT-4>CMT-7. Thus the non-antimicrobial actions of the chemically modified analogues of tetracyclines have shown remarkably better mechanisms to those of agents with established anti-inflammatory/antioxidant potential. These findings clarify the multi-faceted actions of tetracyclines which are unique amongst antimicrobials, with therapeutic applications in periodontal and metabolic diseases. Hence, the present review describes the role of chemically modified tetracyclines in the management of periodontal diseases.

scholarly journals Upregulation of Interleukin 8 by Oxygen-deprived Cells in Glioblastoma Suggests a Role in Leukocyte Activation, Chemotaxis, and Angiogenesis

1997 ◽  
Vol 186 (8) ◽  
pp. 1201-1212 ◽  
Author(s):  
Isabelle Desbaillets ◽  
Annie-Claire Diserens ◽  
Nicolas de Tribolet ◽  
Marie-France Hamou ◽  
Erwin G.  Van Meir
Keyword(s):  
Messenger Rna ◽  
Chemokine Receptors ◽  
Pcr Analysis ◽  
Low Grade ◽  
Normal Brain ◽  
Leukocyte Infiltration ◽  
Reverse Transcription Pcr ◽  
Biological Phenomena ◽  
Inflammatory Stimuli

Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8–binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8–binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2.

scholarly journals Lack of Association betweenTLR4Genetic Polymorphisms and Diabetic Nephropathy in a Chinese Population

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Danfeng Peng ◽  
Jie Wang ◽  
Jiemin Pan ◽  
Rong Zhang ◽  
Shanshan Tang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Chinese Population ◽  
Diabetic Patients ◽  
Low Grade ◽  
Nucleotide Polymorphisms ◽  
Type 2 Diabetic Patients ◽  
Single Nucleotide ◽  
Patients With Diabetes ◽  
Low Grade Inflammation

Objective. Toll-like receptor 4 (TLR4) plays a central role in innate immunity. Activation of innate immune response and subsequent chronic low-grade inflammation are thought to be involved in the pathogenesis of diabetic nephropathy. In this study, we aimed to investigate whetherTLR4variants are associated with diabetic nephropathy in the Chinese population.Methods. Seven tagging single nucleotide polymorphisms (SNPs) ofTLR4based on HapMap Chinese data were genotyped in 1,455 Chinese type 2 diabetic patients. Of these patients, 622 were diagnosed with diabetic nephropathy and 833 were patients with diabetes for over 5 years but without diabetic nephropathy.Results. None of the SNPs and haplotypes showed significant association to diabetic nephropathy in our study. No association between the SNPs and quantitative traits was observed either.Conclusion. We concluded that common variants withinTLR4genes were not associated with diabetic nephropathy in the Chinese type 2 diabetes patients.

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