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Background: Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activitygamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.

The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

Raynaud's Phenomenon (RP) is a paroxysmal vasospastic disorder of small arteries, pre-capillary arteries, and cutaneous arteriovenous shunts of the extremities, typically induced by cold exposure and emotional stress. RP is either primary (PRP) or secondary to systemic sclerosis. In this study we use Control System Theory to model finger thermoregulatory processes in response to a standardized cold challenge (a diagnostic test routinely performed for differential diagnosis of RP). The proposed model is based on a homeostatic negative feedback loop, characterized by five distinct parameters which describe how the control mechanisms are activated and maintained. Thermal infrared imaging data from 14 systemic sclerosis subjects (SSc), 14 PRP, and 16 healthy control subjects (HCS) were processed. HCS presented the fastest active recovery, with the highest gain. PRP presented the slowest and weakest recovery, mostly due to passive heat exchange with the environment. SSc presented an intermediate behavior, with the longest delay of response onset. The estimated model parameters elucidated the level of functional impairment expressed in the various forms of this disease.

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