Background Individuals infected with HIV have an increased risk of developing cardiovascular disease; yet, the underlying mechanisms remain unknown. Recent evidence has implicated the Tie‐2 tyrosine kinase receptor system and its associated ligands ANG1 (angiopoietin 1) and ANG2 (angiopoietin 2) in maintaining vascular homeostasis. In the general population, lower ANG1 levels and higher ANG2 levels are strongly correlated with the development of cardiovascular disease. In this study, we aim to investigate the associations of HIV infection with angiopoietin levels and endothelial dysfunction. Methods and Results In this cross‐sectional study, we compared measures of ANG1, ANG2, and endothelial dysfunction using flow‐mediated vasodilation of the brachial artery in 39 untreated subjects infected with HIV, 47 treated subjects infected with HIV, and 46 uninfected subjects from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort. Compared with uninfected controls, treated individuals infected with HIV had 53.1% lower mean ANG1 levels ( P <0.01) and similar ANG2 levels. On the other hand, untreated individuals infected with HIV had similar ANG1 levels, and 29.2% had higher ANG2 levels ( P <0.01) compared with uninfected controls. When compared with individuals with untreated HIV infection, those with treated HIV infection had 56% lower ANG1 levels ( P <0.01) and 22% lower ANG2 levels ( P <0.01).Both treated and untreated HIV infection were associated with significant impairment in hyperemic velocity, a key measure of microvascular dysfunction (median 61 versus 72 cm/s, P <0.01), compared with uninfected controls (median 73 cm/s). This difference persisted after adjustment for ANG1 and ANG2 levels. Interestingly, when compared with untreated individuals infected with HIV, treated individuals infected with HIV had worse hyperemic velocity (−12.35 cm/s, P =0.05). In contrast, HIV status, ANG1 levels, and ANG2 levels were not associated with macrovascular dysfunction as measured by flow‐mediated dilatation and brachial artery diameter, 2 other measures of vascular homeostasis. Conclusions HIV infection affects the balance between levels of ANG1 and ANG2 and may disturb endothelial homeostasis through disruption of vascular homeostasis. Individuals with treated HIV had decreased ANG1 levels and similar ANG2 levels, whereas individuals with untreated HIV had similar ANG1 levels and increased ANG2 levels, suggesting that treatment status may alter the balance between ANG1 and ANG2. HIV also promotes endothelial dysfunction via impairment of microvascular dysfunction, independent of the Tie‐2 receptor system; the finding of worse microvascular dysfunction in the setting of treated HIV infection may reflect the impact of viral persistence on the microvasculature or toxicities of specific antiretroviral regimens. Further research to clarify the mechanism of HIV‐mediated endothelial dysfunction is necessary to advance treatment of cardiovascular complications of HIV infection.
Researches done on the use of statins during the last two decades have shown conflicting results in their effects on DM, Cardiac, liver and Kidney functions.Six forms of statins are being prescribed as a preventive measure to reduce the incidence of cardiovascular morbidity and mortality; but statin use have also shown alternations in DM, liver and Kidney function.The latest observations relates to cancer prevention/induction. Statins prescriptions are done mostly for elderly patients in order to reduce lipid profile mostly Total cholesterol and LDL levels.Studies have shown that statins use affects muscular function, induce prediabetes, and alter liver enzymes and affects mitochondrial functions.They may also interact with other medications.Some merits shown in the use of statins include prevention of MCI and strokes.Among the statins used, atorvastatin was found to be very beneficial with minimal side effects with greater beneficial function in maintaining other organ functions.This review article highlights the research findings on the use of statins and its merits and demerits during the last two decades.More clinical trials with large population are required to establish the type of statins to be required for each type of patients and clinical conditions.
Abstract Olig2 is an important transcription factor essential for the specification and differentiation of oligodendrocytes as well as astrocytes and neurons during developmental stages. However, Olig2 distribution pattern and its relationship among different types of glial cells in the adult central nervous system (CNS) are not well characterized. Here, we systematically examined Olig2 expression pattern in combination with major markers of neurons and glial cells throughout the brain and spinal cord in the adult mice. As expected, Olig2 is universally expressed in oligodendrocytes and oligodendrocyte precursor cells (OPCs), but not in neurons or microglia. Interestingly, we discover a subpopulation of Olig2-positive astrocytes that are highly enriched in some specific regions including the olfactory bulb, thalamus, midbrain, medulla, and spinal cord in the adult mice. Moreover, OPCs have high expression level of Olig2, whereas oligodendrocytes and astrocytes have similar level of Olig2 expression. Our results suggest that a distinct population of Olig2-positive astrocytes are highly concentrated in discrete regions in the adult CNS. Investigating the functional significance of these Olig2 + astrocytes in both resting state and pathological state of the brain and spinal cord may broaden our understanding on astrocytic heterogeneity and functions.
Alzheimer's disease (AD) is a progressive and irreversible brain disorder with extensive neuronal loss in the neocortex and hippocampus. Current therapeutic interventions focus on the early stage of AD but lack effective treatment for the late stage of AD, largely due to the inability to replenish the lost neurons and repair the broken neural circuits. In this study, by using engineered adeno-associated virus vectors that efficiently cross the blood-brain-barrier in the mouse brain, a brain-wide neuroregenerative gene therapy is developed to directly convert endogenous astrocytes into functional neurons in a mouse model of AD. It is found that ≈500 000 new neurons are regenerated and widely distributed in the cerebral cortex and hippocampus. Importantly, it is demonstrated that the converted neurons can integrate into pre-existing neural networks and improve various cognitive performances in AD mice. Chemogenetic inhibition of the converted neurons abolishes memory enhancement in AD mice, suggesting a pivotal role for the newly converted neurons in cognitive restoration. Together, brain-wide neuroregenerative gene therapy may provide a viable strategy for the treatment of AD and other brain disorders associated with massive neuronal loss.
Background and Objective This study aimed to report retinal displacement incidence following rhegmatogenous retinal detachment (RRD) repair with pars plana vitrectomy (PPV), scleral buckle (SB), or combined SB/PPV. Patients and Methods A single-center, case series using Optos fundus autofluorescence (FAF) images was performed after RRD repair between April 2020 and February 2022. Retinal displacement was identified by imprinted retinal vessels on FAF imaging. Results One hundred ninety-four eyes were included. Ninety-seven (50.0%) eyes underwent PPV, 46 (23.7%) underwent SB, and 51 (26.3%) underwent SB/PPV. A total of 25/194 eyes (12.9%) had retinal vessel imprinting on FAF imaging consistent with retinal displacement. The SB/PPV group (9/51, 17.6%) and the PPV group (15/97, 15.5%) had significantly higher displacement rates when compared to the SB group (1/46, 2.2%; P = 0.017, P = 0.021, respectively). Conclusions Retinal displacement after RRD repair is more prevalent after PPV. There was a low rate of displacement with SB. Retinal displacement was not associated with a visual acuity difference. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:560–566.]
1,5 AG is a six carbon chain monosaccharide and is one of the major polyols present in humans. The approximate normal levels of 1,5AG are about 20 -40 µg/mL. The main source of 1,5AG is diet containing carbohydrates, and this 1,5AG undergoes similar metabolic pathways like other saccharides and is distributed in all organs and tissues. Once DM is confirmed and treatment initiated, it is important to monitor glycemic control at regular intervals of time. While HbA1c has been used as a gold standard to monitor diabetic control during the preceding 2-3 months, GA and FA were used to monitor short time glycemic control. But none of the above three serves to monitor glycemic excursion after meals. 1,5AG has been emerging as an alternative short-term diabetic control monitoring marker to assess short term glycemic excursions. 1,5 AG has also been found to be useful to monitor CVD, CLD patients as well in the clinical usefulness of subtypes of DM. This review article gives a condensed version of research findings during the last two decades and will be very useful for future researchers to expand the clinical usefulness of 1,5AG in other areas of human health.
