Regulation of translation in response to iron deficiency in human cells.

Protein synthesis is a highly energy-consuming process that is downregulated in response to many environmental stresses or adverse conditions. Studies in the yeast Saccharomyces cerevisiae have shown that bulk translation is inhibited during adaptation to iron deficiency, which is consistent with its requirement for ribosome biogenesis and recycling. Although iron deficiency anemia is the most common human nutritional disorder, how iron modulates translation in mammals is poorly understood. Studies during erythropoiesis have shown that iron bioavailability is coordinated with globin synthesis via bulk translation regulation. However, little is known about the control of translation during iron limitation in other tissues. Here, we investigated how iron depletion affects protein synthesis in human osteosarcoma U-2 OS cells. By adding an extracellular iron chelator, we observed that iron deficiency limits cell proliferation, induces autophagy, and decreases the global rate of protein synthesis. Analysis of specific molecular markers indicates that the inhibition of bulk translation upon iron limitation occurs through the eukaryotic initiation factor eIF2α and mechanistic target of rapamycin (mTOR) pathways. In contrast to other environmental and nutritional stresses, iron depletion does not trigger the assembly of messenger ribonucleoprotein stress granules, which typically form upon polysome disassembly.

Pancreatic panniculitis revisited: A series of 34 patients.

BACKGROUND: Pancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue. METHODS: In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records. RESULTS: A total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore-Hoeppli phenomenon. CONCLUSIONS: We present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore-Hoeppli is an additional clue to its diagnosis.

A comprehensive review on pathogenesis, associations, clinical findings, and treatment of livedoid vasculopathy.

Livedoid vasculopathy (LV) is a thrombo-occlusive vasculopathy that involves the dermal vessels. Clinically, it is characterized by the presence of painful purpuric ulcers on the lower extremities. Histopathologically, it shows intraluminal fibrin deposition and thrombosis, segmental hyalinization, and endothelial proliferation. It is important to notice that the term "atrophie blanche" is descriptive and it includes not only patients with LV but also patients with a combination of vasculitis and vasculopathy, that is, LV and medium-sized vasculitis such as cutaneous polyarteritis nodosa (PANc). Diagnosis is based on a proper clinicopathological correlation, excluding the main differential diagnosis and considering vasculitis as a mimicker or concomitant diagnosis. Coagulation disorders must also be studied although they are not found in all LV. Its frequency is reviewed as well. Treatment of LV is challenging, and different therapies have been attempted. Among them, pain management, wound care, control of cardiovascular risk factors, and both antiplatelets and anticoagulants, mostly rivaroxaban, are the main therapies used. These different therapies as well as their degree of evidence are reviewed.