Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension.

Introduction: Type II diabetes mellitus (T2DM) is a metabolic disorder that poses a serious health concern worldwide due to its rising prevalence. Hypertension (HT) is a frequent comorbidity of T2DM, with the co-occurrence of both conditions increasing the risk of diabetes-associated complications. Inflammation and oxidative stress (OS) have been identified as leading factors in the development and progression of both T2DM and HT. However, OS and inflammation processes associated with these two comorbidities are not fully understood. This study aimed to explore changes in the levels of plasma and urinary inflammatory and OS biomarkers, along with mitochondrial OS biomarkers connected to mitochondrial dysfunction (MitD). These markers may provide a more comprehensive perspective associated with disease progression from no diabetes, and prediabetes, to T2DM coexisting with HT in a cohort of patients attending a diabetes health clinic in Australia. Methods: Three-hundred and eighty-four participants were divided into four groups according to disease status: 210 healthy controls, 55 prediabetic patients, 32 T2DM, and 87 patients with T2DM and HT (T2DM+HT). Kruskal-Wallis and χ2 tests were conducted between the four groups to detect significant differences for numerical and categorical variables, respectively. Results and discussion: For the transition from prediabetes to T2DM, interleukin-10 (IL-10), C-reactive protein (CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), humanin (HN), and p66Shc were the most discriminatory biomarkers, generally displaying elevated levels of inflammation and OS in T2DM, in addition to disrupted mitochondrial function as revealed by p66Shc and HN. Disease progression from T2DM to T2DM+HT indicated lower levels of inflammation and OS as revealed through IL-10, interleukin-6 (IL-6), interleukin-1ß (IL-1ß), 8-OHdG and oxidized glutathione (GSSG) levels, most likely due to antihypertensive medication use in the T2DM +HT patient group. The results also indicated better mitochondrial function in this group as shown through higher HN and lower p66Shc levels, which can also be attributed to medication use. However, monocyte chemoattractant protein-1 (MCP-1) levels appeared to be independent of medication, providing an effective biomarker even in the presence of medication use. The results of this study suggest that a more comprehensive review of inflammation and OS biomarkers is more effective in discriminating between the stages of T2DM progression in the presence or absence of HT. Our results further indicate the usefulness of medication use, especially with respect to the known involvement of inflammation and OS in disease progression, highlighting specific biomarkers during disease progression and therefore allowing a more targeted individualized treatment plan.

Subthalamic nucleus deep brain stimulation induces nigrostriatal dopaminergic plasticity in a stable rat model of Parkinson's disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been a highly effective treatment option for middle to late stage Parkinson's disease for decades. Though, the underlying mechanisms of action, particularly effects on the cellular level, remain in part unclear. In the context of identifying disease-modifying effects of STN-DBS by prompting cellular plasticity in midbrain dopaminergic systems, we analyzed neuronal tyrosine hydroxylase and c-Fos expression in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). METHODS: We applied 1 week of continuous unilateral STN-DBS in a group of stable 6-hydroxydopamine (6-OHDA) hemiparkinsonian rats (STNSTIM) in comparison to a 6-OHDA control group (STNSHAM). Immunohistochemistry identified NeuN+, tyrosine hydroxylase+ and c-Fos+ cells within the SNpc and VTA. RESULTS: After 1 week, rats in the STNSTIM group had 3.5-fold more tyrosine hydroxylase+ neurons within the SNpc (P = 0.010) but not in the VTA compared to sham controls. There was no difference in basal cell activity as indicated by c-Fos expression in both midbrain dopaminergic systems. CONCLUSION: Our data support a neurorestorative effect of STN-DBS in the nigrostriatal dopaminergic system already after 7 days of continuous STN-DBS in the stable Parkinson's disease rat model without affecting basal cell activity.

Human SHC-transforming protein 1 and its isoforms p66shc: A novel marker for prediabetes.

AIMS: Prediabetes is a multifactorial condition. Current guidelines for diabetes screening recommend either the use of glycated hemoglobin (HbA1c), or blood glucose level (BGL). This research aimed to identify if p66shc a component of the Human SHC-Transforming Protein 1 (Shc1), a mitochondrial associated oxidative stress biomarker, is significantly altered in patients with elevated BGL. Furthermore, we evaluated if inflammatory and oxidative stress markers, such as p66shc, are a useful addition to the regularly used biomarkers to increase sensitivity for identification of prediabetes. METHODS: All participants attended the Diabetic Health Screening at Charles Sturt University (CSU), Australia. The cross-sectional clinical study collected demographic and clinical variables from 346 participants and classified into control or prediabetes based on fasting BGL. Blood and urine samples were analyzed for oxidative stress and inflammation markers. Logistic regression was used to compare multidimensional diagnostic models for prediabetes, including p66shc/Shc1, to the current HbA1c-only model in terms of sensitivity, specificity and predictive accuracy. Significance was set at P ≤ 0.05. RESULTS: A significant decrease of p66shc/Shc1 was determined in prediabetes compared to controls (P ≤ 0.05). HbA1c testing resulted in an accuracy of 62%, while adding p66shc and triglycerides increased predictive accuracy to 88.05%. When HbA1c was omitted and Shc1 was combined with 8-hydroxy-2'-deoxyguanosine (8-OHdG) and monocyte chemo-attractant protein-1 (MCP-1), a predictive accuracy of 89.5% was achieved. CONCLUSION: Our findings showed a major improvement of sensitivity to identify prediabetes by including oxidative stress and inflammatory biomarkers underlining beneficial diagnostic information, which most likely improves prevention and early treatment options in prediabetes.

The Impact and Consequences of SARS-CoV-2 Pandemic on a Single University Dermatology Outpatient Clinic in Germany.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) affects health care systems globally and leads to other challenges besides infection and its direct medical consequences. The aim of this study was to investigate the impact of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic on the university dermatology outpatient clinic (UDOC) of the Technical University of Munich, Germany. We analyzed datasets from 2015 until 2020 extracted from the hospital information system database and our documented outpatient files regarding patient numbers, gender, age, and diagnoses. In 2020, case numbers of outpatient care declined significantly (p = 0.021) compared to previous years and was related to the timing of political announcements answering SARS-CoV-2 pandemic. Additionally, during calendar week 10 to 15-the peak time of the spread of COVID-19 in Germany-the proportion of patients missing their consultation was significantly higher in 2020 than in 2019 (22.4% vs. 12.4%; p < 0.001). Gender-associated differences regarding absences were not detected, but patients aged 85 years or older were significantly more likely to miss their consultation compared to all other age groups (p = 0.002). Regarding different disease clusters, patients with chronic inflammatory skin diseases and infectious and malignant diseases were more likely to miss their consultation (p = 0.006). Noticeably, less patients with malignant diseases, and particularly malignant melanoma, were registered during this pandemic. Our data support the hypothesis that medically constructive prioritization might not be implemented properly by patients themselves. Identifying missed patients and catching up on their medical care apart from COVID-19 will pose an enormous challenge for health care systems globally.