Public health campaigns and obesity - a critique

<p>Abstract</p> <p>Background</p> <p>Controlling obesity has become one of the highest priorities for public health practitioners in developed countries. In the absence of safe, effective and widely accessible high-risk approaches (e.g. drugs and surgery) attention has focussed on community-based approaches and social marketing campaigns as the most appropriate form of intervention. However there is limited evidence in support of substantial effectiveness of such interventions.</p> <p>Discussion</p> <p>To date there is little evidence that community-based interventions and social marketing campaigns specifically targeting obesity provide substantial or lasting benefit. Concerns have been raised about potential negative effects created by a focus of these interventions on body shape and size, and of the associated media targeting of obesity.</p> <p>Summary</p> <p>A more appropriate strategy would be to enact high-level policy and legislative changes to alter the obesogenic environments in which we live by providing incentives for healthy eating and increased levels of physical activity. Research is also needed to improve treatments available for individuals already obese.</p

Gelatinases A and B are expressed in late lesions in autoimmune bullous disorders

Gelatinases (or metalloproteinase or collagenases) are involved in remodelling the extracellular matrix in several skin disorders. Previous reports show that the 72 kDa (Gelatinase A), the 92 kDa collagenase (Gelatinase B) and their inhibitors TIMP-2 and TIMP-1 respectively are overexpressed in tumor invasion and metastasis, granuloma annulare, necrobiosis lipoidica diabeticorum and bullous pemphigoid. Usually their natural inhibitors, TIMP-1 and TIMP-2, are inversely related to the production of the 72 kDa and 92 kDa proteins. 8 patients affected by Bullous Pemphigoid (BP) and 8 patients affected by Pemphigus Vulgaris (PV) were biopsized in perilesional areas of young lesions and in lesional areas of old lesions. Materials were snap frozen in liquid nitrogen until use. Antibodies to 72 kDa, 92 kDa, TIMP-1, TIMP-2, CD44, laminin, collagen type I, III, IV, VII were used and evidentiated by the avidin-biotin immunoperoxidase technique. mRNA expression for Gelatinases and their inhibitors were also analyzed by RT-PCR. In all patients we found gelatinases expression only in the late lesions. A different expression was found between the two diseases, the 92 kDa protein and its inhibitor TIMP-1 were positive in both PB and PV whereas the 72 kDa form and its inhibitor TIMP-2 were evident only in PB. By RT-PCR we show that the 72 kDa mRNA was expressed exclusively in the dermis, on the contrary the 92 kDa was present in epidermis and dermis. No signals were detected in the early phase of blistering suggesting a role of gelatinases in re-epithelization but not in blistering where other proteases play a major role. The differential expression of Gelatinases and their inhibitors is probably under a cytokine network control

Facial granuloma [IL GRANULOMA FACIALE]

Granuloma faciale is classified as a leukocytoclastic vasculitis. It typically occurs on the face as a reddish, elevated, well circumscribed, usually solitary nodule. Occasionally multiple lesions appear. The lesions are histologically characterized by a dense dermal inflammatory infiltrate separated from epidermis by a 'grenz zone' of uninvolved dermis. A case of a 50-year old man with a 3 cm nodular lesion on the chin and a papular lesion on the cheek is reported. In three years the lesions showed a very slow enlargement. No other diseases were associated. The histology was typical for granuloma faciale; an immunohistochemical study showed the presence of CD4 + CD45RO + cells with no CD4+CD45RA+ cells. This patient underwent an excision of the lesions, but after two years there was a recurrence of the lesion on the chin and two new lesions appeared on the cheek. Intralesional injection of triamcinolone (5 mg/ml) induced a regression of the lesions with no other recurrence

TH2 cytokines profile in severe adult atopic dermatitis [PROFILO DI CITOCHINE A TIPO TH2 IN CORSO DI DERMATITE ATOPICA GRAVE DELL'ADULTO]

Atopic dermatitis is a disorder in which both type I and type IV reactions are involved. The disease is characterized by eczematous lesions and an aspecific infiltrate, often rich in eosinophils. Inflammatory infiltrate is constituted of T cells of the TH1 subset, but many authors showed that the TH2 subtype is important in the early phase of the disease. On the basis of our and of other group studies we investigated, at a molecular level, the mRNA expression of IL-4, IL-5, IL-2 and IFN-γ, in order to define the immunological pattern of the inflammatory infiltrate. IL-2 and IFN-γ are important mediators of delayed immunity, whereas IL-4 and IL-5 are involved especially in early immunity mechanisms, but can also participate in type IV reaction. Interleukin-4 and IL-5 are both produced by the T helper-2 lymphocyte subset. On the other hand the TH1 subset produces IL-2 and IFN-γ. IL-4 and IL-5 have many functions that could be summarized in eosinophils chemoattraction and maturation, and support to immunoglobulin-E production. IL-4 and IFN-γ have opposite functions on IgE production and are counter regulatory each other. 11 patients affected by atopic dermatitis and 5 normal patients have been biopsied. Biopsies and blood samples were taken within 48 hours from the appearance of new lesions and snap frozen in liquid nitrogen. Messenger RNA was extracted from biopsies, reverse transcribed and amplified. β-actin was used as a semiquantitative control. All patients showed a TH2-like cytokine pattern with IL-4 and IL-5 expression in both blood and skin samples. Two patients, biopsied several days later than the others, showed a reduction of IL-4 and IL-5 with an increased production of IL-2 and IFN-γ. We suggest that after an early immune reactions supported by a TH2-like cytokine secrection, there is a switching in the cytokine pattern to a TH1-like cytokine pattern

Gelatinases A and B are expressed in late lesions in autoimmune bullous disorders

Gelatinases (or metalloproteinase or collagenases) are involved in remodelling the extracellular matrix in several skin disorders. Previous reports show that the 72 kDa (Gelatinase A), the 92 kDa collagenase (Gelatinase B) and their inhibitors TIMP-2 and TIMP-1 respectively are overexpressed in tumor invasion and metastasis, granuloma annulare, necrobiosis lipoidica diabeticorum and bullous pemphigoid. Usually their natural inhibitors, TIMP-1 and TIMP-2, are inversely related to the production of the 72 kDa and 92 kDa proteins. 8 patients affected by Bullous Pemphigoid (BP) and 8 patients affected by Pemphigus Vulgaris (PV) were biopsized in perilesional areas of young lesions and in lesional areas of old lesions. Materials were snap frozen in liquid nitrogen until use. Antibodies to 72 kDa, 92 kDa, TIMP-1, TIMP-2, CD44, laminin, collagen type I, III, IV, VII were used and evidentiated by the avidin-biotin immunoperoxidase technique. mRNA expression for Gelatinases and their inhibitors were also analyzed by RT-PCR. In all patients we found gelatinases expression only in the late lesions. A different expression was found between the two diseases, the 92 kDa protein and its inhibitor TIMP-1 were positive in both PB and PV whereas the 72 kDa form and its inhibitor TIMP-2 were evident only in PB. By RT-PCR we show that the 72 kDa mRNA was expressed exclusively in the dermis, on the contrary the 92 kDa was present in epidermis and dermis. No signals were detected in the early phase of blistering suggesting a role of gelatinases in re-epithelization but not in blistering where other proteases play a major role. The differential expression of Gelatinases and their inhibitors is probably under a cytokine network control

IL-1α, IL-6 and TNF-α in cutaneous lesions of lupus erythematosus are inhibited by topical application of calcipotriol

Lupus Erythematosus (LE) is an autoimmune disorder with an unknown. etiology and pathogenesis. Skin lesions of LE express several cytokines which correlate to histological findings such as IL-1 and IL-6 which are mediators of epidermal growth and proliferation. Skin lesions of LE are generally treated with immunosuppressive agents such as oral or topically applied corticosteroids. Recently a new drug, calcipotriol, a vitamin D3 analogue has been useful in treatment of psoriasis with no adverse effect on calcium metabolism. This drug shares immunomodulatory effects with vit. D3 by inhibiting several cytokines produced by keratinocytes. In order to test the clinical effectiveness of calcipotriol in cutaneous lesions of LE we have investigated several proinflammatory cytokines such as: IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, MCP-1, TNF-α. Using an avidin-biotin immunoperoxidase system we have found IL-1 in both forms, IL-6 and TNF-α in basal keratinocytes in patients affected with LE, after treatment they were reverted to normal. This inhibition is induced at a molecular level as demonstrated by reduced IL-1, IL-6 and TNFα mRNA expression. This is the first report showing that calcipotriol is effective in cutaneous lesions of LE and suggesting that this action is due to an inhibition of protein synthesis and mRNA expression for IL-1α, IL-6 and TNFα

KSHV mRNA expression in tissue samples from Kaposi's sarcoma

Kaposi's sarcoma (KS) etiology has generally been thought to be of multifactorial origin involving genetic predisposition, geographical factors, and endogenous influences such as angiogenic factors. Recently a new herpesvirus later called with the descriptive name of Kaposi's sarcoma associated Herpes Virus (KSHV), had been discovered in tissue samples of KS skin lesions and in peripheral blood of these patients. KSHV has been found in all types of Kaposi's sarcoma and many studies give strong basis to affirm that this virus has a role in the etiology of this disease. We performed a molecular biology study to investigate the presence and the replication of this virus in four patients affected by KS; 3 with Classical KS form (CKS) and 1 with Iatrogenic KS associated with multiple myeloma (IKS). Two specimens of CKS and the IKS one were taken from recent onset lesions of rapidly progressive disease at a papule-nodules stage, while another specimen of CKS was from a long-standing lesion (more than 20 years) without any tendency for progression. All patients were HIV negative. Control skin samples were obtained from patients undergoing plastic surgery. Both for the Polymerase chain reaction (PCR) and for the reverse transcriptase-poymerase chain reaction (RT-PCR) the primers KS1 and KS2 were used, which amplify a 233 bp sequence from KSHV genome. All three specimens from recent onset lesion resulted positive for KHSV presence at the PCR and also at the RT-PCR demonstrating an active replication of KSHV in these lesions. Instead both the PCR and the RT-PCR of the long standing CKS lesion failed to demonstrate respectively the presence and the replication of the virus even if the numbers of the cycles were raised. Our report is the first in which not only DNA but also KSHV mRNA was demonstrated, showing the active replication of the virus in lesions of recent onset. The negative result in the long standing KS lesion could be just a false negative, giving the extreme sensibility of PCR, on the other hand it could be that either the presence of the virus nor its replication is necessary for the disease to maintain itself after long periods and a particular cytokine network is responsible for the long lasting 'slowly developing' disease sometimes seen in Classic KS. Our findings on the replication of KSHV in recent and progressive disease further support the hypothesis that KSHV reactivation or infection could take place in particular immunological conditions and thus that KSHV could have an early causative role in the development of KS of different origin

IL-1α, IL-6 and TNF-α in cutaneous lesions of lupus erythematosus are inhibited by topical application of calcipotriol

Lupus Erythematosus (LE) is an autoimmune disorder with an unknown. etiology and pathogenesis. Skin lesions of LE express several cytokines which correlate to histological findings such as IL-1 and IL-6 which are mediators of epidermal growth and proliferation. Skin lesions of LE are generally treated with immunosuppressive agents such as oral or topically applied corticosteroids. Recently a new drug, calcipotriol, a vitamin D3 analogue has been useful in treatment of psoriasis with no adverse effect on calcium metabolism. This drug shares immunomodulatory effects with vit. D3 by inhibiting several cytokines produced by keratinocytes. In order to test the clinical effectiveness of calcipotriol in cutaneous lesions of LE we have investigated several proinflammatory cytokines such as: IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, MCP-1, TNF-α. Using an avidin-biotin immunoperoxidase system we have found IL-1 in both forms, IL-6 and TNF-α in basal keratinocytes in patients affected with LE, after treatment they were reverted to normal. This inhibition is induced at a molecular level as demonstrated by reduced IL-1, IL-6 and TNFα mRNA expression. This is the first report showing that calcipotriol is effective in cutaneous lesions of LE and suggesting that this action is due to an inhibition of protein synthesis and mRNA expression for IL-1α, IL-6 and TNFα

'Suction split' as a routine method to differentiate epidermolysis bullosa acquisita from bullous pemphigoid

Background and Design: Epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP) are diseases with similar clinical, histological, and immunofluorescent findings. Diagnosis requires the use of immunoelectron microscopy, immunoprecipitation or immunoblotting, but in recent years the differential diagnosis has been based on a cheaper technique named salt split skin. This study demonstrates that with a suction blister the fracture is at the same level as that obtained with the sodium split method anti that it is also faster and cheaper. Suction blisters on normal skin and autoimmune perilesional bullous lesions, obtained with a hand vacuum pump, were studied by direct immunofluorescence and electron microscopy to evaluate the level of the split on normal suction split skin. Normal human split skin was also used as a substrate for an indirect immunofluorescent study using sera of patients with BP (68 sera), EBA (10 sera) and cicatricial pemphigoid (CP) (16 sera). Direct immunofluorescent examination was also done on perilesional skin after artificial separation obtained with a hand-vacuum pump in patients with the same diseases listed above (32 BP, 11 CP, 6 EBA). Results: On normal human skin split by suction or sodium chloride (NaCl; 1 mol/l) direct immunofluorescence and electron microscopy demonstrated that the split is at the lamina lucida level. Indirect immunofluorescent study of both normal human skin and perilesional skin split using suction as a substrate showed IgG deposits localized on the floor of the suction blister in all cases of EBA, whereas in over 88% of cases of BP and in over 62% of CP the IgG were localized on the roof. Similar results were obtained with direct immunofluorescence in perilesional skin. Conclusions: 'Suction split' represents a simple technique to differentiate EBA from BP. This method provides final response in a few hours compared to at least 1-2 days with the sodium split method. Furthermore, the suction split method is cheaper and the tissue can be re-utilized for molecular biology and immunohistochemical studies