Subcutaneous panniculitic T-cell lymphoma (SPTL) is a rare variant of cutaneous T-cell lymphoma where lymphoma cells infiltrate preferentially into subcutaneous tissue. Five cases of SPTL were seen during the period from 2001-2004 at the Department of Dermatology, Hospital Kuala Lumpur. All five presented with multiple subcutaneous nodules on the face, trunk and limbs of one week to six months duration with associated fever and loss of weight. Physical examination showed multiple tender, erythematous indurated plaques and subcutaneous nodules on their face, trunk and limbs. One patient also presented with unhealing ulcerated nodules. Two patients had hepatosplenomegaly and one hepatomegaly. Two patients had pancytopaenia while the other three had leucopaenia. One patient had deranged liver function. Out of the five patients, three had bone marrow examination with haemophaegocytosis in two and one hypocellular marrow. Skin biopsy of all patients showed infiltration with atypical lymphoid cells in the upper dermis and subcutaneous fat. These neoplastic cells showed positivity for CD3 and CD30 in three patients with CD8, TIA-1 and LCA (Leucocyte common antigen) being positive in one patient. One patient treated with prednisolone and subcutaneous Roferon 3Mu three times a week since 2001 was in remission. Two patients who were planned for chemotherapy had deteriorated rapidly and succumbed to septicaemia from pancytopaenia. Subcutaneous panniculitic T-cell lymphoma has been reported to show two distinct clinical presentations. The first is characterized by an indolent course with good prognosis and the second with rapid clinical deterioration, haemophaegocytosis and death. Both presentations were seen in our five patients seem to demonstrate these two subtypes of SPTL.
Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle.