Dysgeusia and Chronic Kidney Disease: A Scoping Review.

Dysgeusia is a common altered taste perception in chronic kidney disease patients. The study aims to identify available treatments for educating, screening, and clinically managing dysgeusia in this population. A scoping review was conducted following the protocol of Arksey and O'Malley, incorporating the Joanna Briggs Institute methodology, and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Among the 424 identified records, 13 studies were included. Screening methodologies, educational strategies, particularly a hospital-based program focusing on salt reduction, showed a significant improvement in dysgeusia (P < .001). The identified clinical treatments exclusively included oral zinc supplementation, with dosages ranging from 50 to 220 mg, reporting heterogeneous results not consistent across different studies. The personalized management of dysgeusia associated with chronic kidney disease is crucial, requiring targeted education and treatment protocols to prevent and address nutritional complications such as malnutrition.

Acute rosiglitazone treatment during reperfusion after hyperglycemic stroke is neuroprotective not vascular protective.

Reperfusion therapy for ischemic stroke can cause secondary brain injury, especially under hyperglycemic (HG) conditions. Here we investigated the effect of acute treatment with rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, prior to postischemic reperfusion, on stroke outcome during HG stroke. Male Wistar rats that were either normoglycemic (NG) or HG by STZ (50 mg/kg; for 5-6 days) underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Animals were treated i.v. with rosiglitazone (1mg/kg; n=16), rosiglitazone (1mg/kg) + the free radical scavenger Tempol (50mg/kg; n=10) or vehicle (n=16) ten minutes prior to reperfusion and infarct volume, edema formation and cerebral blood flow (CBF) were measured. Compared to NG, HG stroke significantly increased infarct volume from 5.2±3.0% vs. 14.7±3.6% (p<0.05). Rosiglitazone prevented the increased infarct volume induced by HG that was only 6.9±2.0% (p<0.05 vs. HG) but did not have any effect on edema formation that was increased by 3.0% in both HG vehicle and rosiglitazone-treated ipsilateral vs. contralateral hemispheres (p<0.05). Combined treatment of rosiglitazone + Tempol did not significantly change brain water content that remained 2.2% greater than contralateral (p<0.05), but reversed the neuroprotective properties of rosiglitazone in HG MCAO animals such that infarct volume was 14.3±4.4% (p>0.05 vs. vehicle). The lack of an effect of combined treatment of rosiglitazone + Temple may be due to a decrease in reperfusion CBF that was only 60% of baseline (p<0.01) compared to 82% and 89% for HG vehicle and rosiglitazone treated animals (p>0.05). In conclusion, acute rosiglitazone treatment prior reperfusion was neuroprotective but not vascular protective during HG stroke.

Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular dysfunction and infarction during mild but not severe hyperglycemic stroke.

We investigated mechanisms by which circulating factors during hyperglycemic (HG) stroke affect cerebrovascular function and the role of peroxynitrite in stroke outcome. Middle cerebral arteries (MCAs) were isolated from male Wistar rats and perfused with plasma from rats that were hyperglycemic for 5 to 6 days by streptozotocin and underwent either MCA occlusion (HG MCAO) or Sham surgery (HG Sham) compared with MCA perfused with physiologic saline (No plasma). Myogenic responses and endothelial function were compared in untreated MCA (n=8/group) or with inhibitors of NADPH oxidase (apocynin; n=8), peroxynitrite (FeTMPyP; n=8) or endothelin-1 (ET-1)(A) (BQ-123; n=8). Finally, animals were treated in vivo before reperfusion after mild (<68% cerebral blood flow (CBF) decrease) or severe (>68% CBF decrease) MCAO with FeTMPyP (n=12) or vehicle (n=12) and CBF and infarction measured. The HG MCAO plasma increased tone in MCA versus No plasma (P<0.05) that was reversed by FeTMPyP, but not by apocynin or BQ-123. The HG Sham plasma also increased tone in MCA (P<0.05) that was reversed by BQ-123 only. In vivo, FeTMPyP was neuroprotective during mild, but not severe ischemia. These results show that circulating factors in plasma can affect cerebrovascular function through peroxynitrite generation and ET-1. In addition, peroxynitrite decomposition improves stroke outcome acutely during mild, but not severe HG ischemia.

Vascular Protection Following Cerebral Ischemia and Reperfusion.

Despite considerable research that has contributed to a better understanding of the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed. The only effective treatment for ischemic stroke is rapid recanalization of an occluded vessel by dissolving the clot with tissue plasminogen activator (tPA). However, stroke adversely affects vascular function as well that can cause secondary brain injury and limit treatment that depends on a patent vasculature. In middle cerebral arteries (MCA), ischemia/reperfusion (I/R) cause loss of myogenic tone, vascular paralysis, and endothelial dysfunction that can lead to loss of autoregulation. In contrast, brain parenchymal arterioles retain considerable tone during I/R that likely contributes to expansion of the infarct into the penumbra. Microvascular dysregulation also occurs during ischemic stroke that causes edema and hemorrhage, exacerbating the primary insult. Ischemic injury of vasculature is progressive with longer duration of I/R. Early postischemic reperfusion has beneficial effects on stroke outcome but can impair vascular function and exacerbate ischemic injury after longer durations of I/R. This review focuses on current knowledge on the effects of I/R on the structure and function of different vascular segments in the brain and highlight some of the more promising targets for vascular protection.