Infection imaging using [18F]FDG-labelled white blood cell positron emission tomography–computed tomography

Localizing the sites of infection in the body is possible in nuclear medicine using a variety of radiopharmaceuticals that target different components of the infective and inflammatory cascade. Gamma(γ)-emitting agents such as [67Ga]gallium citrate were among the first tracers used, followed by development of positron-emitting tracers like 2-deoxy-2-[18F]fluoro-D-glucose (¹⁸F-FDG). Though these tracers are quite sensitive, they have limited specificity for infection due to their concentration in sites of non-infective inflammation. White blood cells (WBC) labelled with γ or positron emitters have higher accuracy for differentiating the infective processes from the non-infective conditions that may show positivity with tracers such as ¹⁸F-FDG. We present a pictorial review of potential clinical applications of PET/CT using ¹⁸F-FDG labelled WBC.     

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.     

Giant Cell Lesions Associated with Primary Hyperparathyroidism

Aims and Objective

To evaluate the prevalence, clinical features, diagnostic laboratory values and treatment outcome of giant cell lesions (brown tumors) associated with primary hyperparathyroidism (PHPT) in oral and maxillofacial region.

Study Design

A 5 year retrospective data was analyzed wherein all histopathologically proven cases of giant cell lesions involving oral and maxillofacial region were evaluated. Out of these cases, those associated with PHPT were tabulated. Correlation was established with other concomitant clinical features and also with the laboratory values of altered serum calcium, phosphate, alkaline phosphate and parathormone. Follow up of these cases after the correction of PHPT was also noted.

Result

Out of 85 cases of histopathologically proven giant cell lesions, five cases were associated with PHPT. There was involvement of maxilla and mandible in one case each. Only frontal bone was involved in two cases. Fifth case had multiple lytic lesions in maxilla and frontal bone. All patients consistently showed very high values of alkaline phosphate and parathormone. Hypercalcemia and hypophosphatemia was noted in four cases. All cases showed regression of the lytic lesion after parathyroidectomy obviating the need for surgical excision of the jaw lesions.

Conclusion

Giant cell lesions (brown tumors) associated with PHPT in oral and maxillofacial region are rare clinical entities. The prevalence of PHPT associated giant cell lesions is 5.9 %. They are clinically, radiologically and histopathologically similar to any other peripheral or central giant cell tumor. Relevant history may alert the clinician and altered biochemical values may help in correlating the oral and maxillofacial findings with the underlying systemic disease. At times, the brown tumor maybe the only presenting sign leading to the diagnosis of PHPT.