Cardiac troponin in ischemic cardiomyocytes: Intracellular decrease before onset of cell death

Aim

Cardiac troponin I (cTnI) and T (cTnT) are the most important biomarkers in the diagnosis of acute myocardial infarction (AMI). Nevertheless, they can be elevated in the absence of AMI. It is unclear if such elevations represent irreversible cardiomyocyte-damage or leakage from viable cardiomyocytes. Our objective is to evaluate whether cTn is released from viable cardiomyocytes in response to ischemia and to identify differences in the release of cTn and its molecular forms.

Methods and results

HL-1 cardiomyocytes (mouse) were subjected to ischemia (modeled by anoxia with glucose deprivation). The total contents and molecular forms of cTn were determined in culture media and cell lysates. Cell viability was assessed from the release of lactate dehydrogenase (LDH). Before the release of LDH, the intracellular cTn content in ischemic cells decreased significantly compared to control (52% for cTnI; 23% for cTnT) and was not matched by a cTn increase in the medium. cTnI decreased more rapidly than cTnT, resulting in an intracellular cTnT/cTnI ratio of 25.5 after 24 h of ischemia. Western blots revealed changes in the relative amounts of fragmented cTnI and cTnT in ischemic cells.

Conclusions

HL-1 cardiomyocytes subjected to simulated ischemia released cTnI and cTnT only in combination with the release of LDH. We find no evidence of cTn release from viable cardiomyocytes, but did observe a significant decrease in cTn content, before the onset of cell death. Intracellular decrease of cTn in viable cardiomyocytes can have important consequences for the interpretation of cTn values in clinical practice.     

Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.     

Intergenerational Sex as a Risk Factor for HIV Among Young Men Who Have Sex with Men: A Scoping Review

An emerging body of evidence suggests that intergenerational sexual partnerships may increase risk of HIV acquisition among young men who have sex with men (YMSM). However, no studies have comprehensively evaluated literature in this area. We applied a scoping review methodology to explore the relationships between age mixing, HIV risk behavior, and HIV seroconversion among YMSM. This study identified several individual, micro-, and meso-system factors influencing HIV risk among YMSM in the context of intergenerational relationships: childhood maltreatment, coming of age and sexual identity, and substance use (individual-level factors); family and social support, partner characteristics, intimate partner violence, connectedness to gay community (micro-system factors); and race/ethnicity, economic disparity, and use of the Internet (meso-system factors). These thematic groups can be used to frame future research on the role of age-discrepant relationships on HIV risk among YMSM, and to enhance public health HIV education and prevention strategies targeting this vulnerable population.     

Acute pancreatitis in peritoneal dialysis: a case report with literature review

Abdominal pain with a discoloured dialysate in a patient on peritoneal dialysis (PD) is usually attributed to infective peritonitis. Although acute pancreatitis (AP) is not usually a complication of end-stage renal disease, some studies suggest an increased risk especially in patients on PD. We report a case of idiopathic AP in a 41-year-old female on PD who presented with abdominal pain, fever, vomiting and a clear dark dialysate. Initial diagnosis of PD-associated infective peritonitis was made but dialysate cultures proved negative. Serum amylase showed a mild rise and computed tomography revealed necrotising pancreatitis. No common risk factors for AP were identified and she was successfully treated with conservative therapy. A literature review was carried out using a PubMed search with the words 'acute pancreatitis and peritoneal dialysis'. The literature search found a total of 94 cases of AP in the setting of PD. In more than a quarter, no cause for AP was found. Serum amylase was normal in 12.8% of episodes. Complications developed in 25 cases, and 28 patients died from the condition. Therefore, AP can be a rare, but serious complication of PD with a high mortality and must be considered in the differential diagnosis of abdominal pain in a PD patient.