Dyslipidemia in Special Populations, the Elderly, Women, HIV, Chronic Kidney Disease and ESRD, and Minority Groups

This chapter discusses the management of dyslipidemia in special patient populations: the elderly, woman and pregnancy, renal disease, human immunodeficiency virus (HIV), and different racial/ethnic groups. In the elderly, dyslipidemia is often underdiagnosed and undertreated. Consideration for potential atherosclerotic risk-reduction benefits, risk of adverse effects, drug-drug interactions, and patient preferences should precede the initiation of statin therapy. Data on pregnant women are lacking and need future research. Dyslipidemia and its effects on the cardiovascular system in chronic kidney disease (CKD), end-stage renal disease (ESRD), and HIV are dynamic and multimodal. These conditions are states of chronic inflammation, where it is difficult to associate quantities of cholesterol types with outcomes. Among all racial groups, Asian Indians, Filipinos, and Hispanics are at a higher risk for dyslipidemia. Genetic differences in statin metabolism may explain this racial/ethnic difference

Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines

<p>Abstract</p> <p>Background -</p> <p>The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the <it>de-novo </it>transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines.</p> <p>Methods -</p> <p>The experimental approach utilized isolated, washed human platelet suspensions and cultured human venous endothelial cells (HUVEC) and human arterial endothelial cells (HAEC) exposed to the proinflammatory cytokines TNF-alpha and/or IFN-gamma, for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity: general mRNA synthesis inhibitors, inhibitors of the NF-kappaB and JAK/STAT pathways, and small interfering F11R-mRNA (siRNAs) to specifically silence the F11R gene.</p> <p>Results -</p> <p>Treatment of inflamed ECs with the inhibitors actinomycin, parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression, indicating the involvement of NF-kappaB and JAK/STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete inhibition of the cytokine-induced upregulation of F11R mRNA and inhibition of detection of the newly- translated F11R molecules in cytokine-inflamed ECs. The functional consequence of the inhibition of F11R transcription and translation was the significant blockade of the adhesion of human platelets to inflamed ECs.</p> <p>Conclusion -</p> <p>These results prove that <it>de novo </it>synthesis of F11R in ECs is required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the <it>de-novo </it>translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke.</p

In vivo data: treatment with the F11R/JAM-A peptide 4D decreases mortality and reduces the generation of atherosclerotic plaques in ApoE-deficient mice

The data in this article focus on the F11 Receptor (F11R/JAM-A; Junctional Adhesion Molecule-A; JAM-A, F11R), a cell adhesion protein constitutively expressed on the membrane surface of circulating platelets and localized within the tight junctions of healthy endothelial cells (ECs). Previous reports have shown that F11R/JAM-A plays a critical role in the adhesion of platelets to an inflamed endothelium due to its’ pathological expression on the luminal surface of the cytokine-inflamed endothelium. Since platelet adhesion to an inflamed endothelium is an early step in the development of atherosclerotic plaque formation, and with time, resulting in heart attacks and stroke, we conducted a long-term, study utilizing the atherosclerosis-prone ApoE-/- mice to attempt a blockade of the formation of atherosclerotic plaques by preventing the adhesion of platelets to the inflamed vasculature in vivo. Utilizing a nonhydrolyzable peptide derived from an amino acid sequence of F11R/JAM-A, peptide 4D, we have shown in culture that the adhesion of platelets to the inflamed endothelial cells could be blocked by peptide 4D. The present data demonstrate the positive health benefits of chronic peptide 4D administration to the atherosclerosis-prone ApoE-/- mice, and provides new information for potential use of this F11R derived peptide in the prevention of atherosclerosis. The data presented in this article provide further experimental support for the study presented in Babinska et al., Atherosclerosis 284 (2019) 92-101

Case Report Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity

Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity

Diabetic Retinopathy: Focus on Minority Populations

Diabetic retinopathy is a major cause of blindness in the United States. With rise of the epidemic of obesity and diabetes in the USA and around the globe, serious and common diabetic complications areevolving as a major public health problem, particularly among minority populations. These populationsare disproportionately affected by diabetes and 2-3 times more likely to develop visually signifi cantcomplications. In this highly illustrated review article, we discuss the diabetic epidemic, highlightingthe biology and the pathophysiologic mechanisms of this disorder on the anatomy of the eye. We alsodiscuss the risk factors and the implications for minority populations. For the health care providers, weprovide cutting edge information and imminently relevant information to help evaluate, manage, and knowwhen to refer their patients to a specialist in ophthalmology to quell the tide of the epidemic.Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/29756128 </p

Atypical Causes of Urinary Tract Obstruction

Acute kidney injury due to urinary tract obstruction invariably suggests lower urinary tract obstruction or bilateral ureteric obstruction since obstruction of a single kidney while the contralateral kidney is normal and not obstructed would not cause a perceptible rise in creatinine. Assuming a total body volume of 42 L, 70 kg male that generates approximately 1400 mg of creatinine daily (20 mg/kg/day) who has complete urinary tract obstruction would experience a 3.33 mg/dL per day increase in serum creatinine. Thus, for an individual who had prior normal renal function and who presents with a creatinine of 30 mg/dL, one could surmise that the obstructive pathology had lasted at least 10 days. However, the rise in serum creatinine is a poor marker of renal injury and subsequent prognosis. Urinary tract obstruction leading to AKI can be due to a variety of causes, and its management is tailored to the underlying etiology. This case series describes the varied clinical course of four patients at our center who experienced AKI from atypical causes of obstructive uropathy. Current and future diagnostic modalities and caveats in the treatment of this disease entity are also discussed

A Case of Acute Colonic Pseudo-Obstruction (Ogilvie’s Syndrome) in a Nonsurgical Patient with Plasma Cell Leukemia

Ogilvie’s syndrome, also known as acute colonic pseudo-obstruction (ACPO), is a rare, nonobstructive dilation of the colon of unclear etiology. We present the case of a patient who presented with Ogilvie’s syndrome and significant hypokalemia due to colonic loss despite repletion. This case report demonstrates the difficulty in diagnosis, treatment, and outcome