In vitro accumulation of technetium-99m-sestamibi in human parathyroid mitochondria.

BACKGROUND: Technetium-99m-sestamibi (sestamibi) is the imaging agent of choice for preoperative parathyroid localization. The subcellular localization of sestamibi uptake in enlarged parathyroid glands in patients with hyperparathyroidism has not been determined. This study investigated the mechanism of retention of sestamibi by human parathyroid tissue. METHODS: Twenty-three freshly harvested and 15 cryopreserved parathyroid glands excised from patients with primary or secondary hyperparathyroidism were analyzed for subcellular localization of Tc-99m-sestamibi. Tissues were incubated with 100 microCi of sestamibi and isolated for mitochondria by differential centrifugation, and the integrity of subcellular fractions was quantified with the mitochondrial enzyme marker, succinate dehydrogenase. RESULTS: Ninety-two percent of sestamibi activity was associated with mitochondria. Furthermore, after adding the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), to fresh parathyroid tissues, 84.96% and 73.86% of sestamibi was released from the mitochondrial and tissue fragment components, respectively. In addition, sestamibi activity in the mitochondrial component of cryopreserved human parathyroid tissue decreased to the same amount as the CCCP-treated group. CONCLUSIONS: These data confirm that mitochondrial activity is the major component of sestamibi uptake by human parathyroid tissue in patients with hyperparathyroidism.     

Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men

We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels.     

Post-mitral valve repair systolic anterior motion produced by non-obstructive septal bulge

Objective: Systolic anterior motion (SAM) may rarely occur after mitral valve reconstruction due to different anatomic factors. Several techniques have been described to reduce the incidence of post-repair SAM, e.g. leaflet sliding plasty. However, SAM can still occur after these special procedures. We reviewed data of patients developing SAM with significant mitral regurgitation due to non-obstructive septal bulge. Methods: During a 2-year period mitral valve repair was performed in 358 patients. Five of 358 (1.4%) patients with a mean age of 52±10.5 years developed post-repair SAM with severe mitral insufficiency due to non-obstructive septal bulge. Data of these patients were analyzed retrospectively and controlled after a mean follow-up of 18±2.7 months. Results: Preoperative echocardiography showed end-diastolic septum diameter of 7, 10, 10, 11 and 15 mm. The ratio between end-diastolic septum diameter and free wall diameter was 1 in four patients and 1.25 in one patient. There was no left ventricular outflow tract obstruction (LVOT). Intraoperative data revealed large myxomatous anterior (four patients) and posterior (three patients) leaflets. Quadrangular resection of posterior leaflet was carried out in four patients and sliding plasty in one patient. Cause for post-repair mitral regurgitation was a non-obstructive septal bulge. During a second pump run septal bulge was resected. Mean aortic cross-clamp time and cardiopulmonary bypass time for this procedure was 15±1.4 and 28±3.1 min, respectively. Mitral regurgitation disappeared in all patients immediately after this procedure. The grade of mitral regurgitation at follow-up was 0–1 in all patients. One patient had subaortic gradient of 36 mmHg. Conclusions: If mitral regurgitation occurs after primary successful mitral repair, septum bulge should always be considered as the primary cause for SAM even there is no preoperative gradient in LVOT. Before performing time-consuming corrective operations to relieve SAM, a septum resection should be carried out during a short second pump run.