A novel method to measure skin mechanical properties with three-dimensional digital image correlation.

BACKGROUND: Measuring skin mechanical properties has been of great interest in the skincare industry. It is a high accuracy and non-invasive optical technique which quantitatively tracks skin movement and deformation under mechanical perturbations. METHODS: A study was conducted with female subjects (25-65 years old). A refined speckle pattern applied onto the skin surface was used for DIC measurements. A unidirectional force pulled the skin at a constant velocity, while the deformation process was quantified by the DIC. Prior to the DIC measurement, Cutometer® readings were taken on the same area. The DIC protocol's reproducibility across multiple pattern applications, the measurement's repeatability, and the sensitivity in differentiating skin mechanical properties were investigated. RESULTS: Subjects were clustered with statistical significance according to their skin mechanical properties described by six DIC metrics (µ [major strain], σ [major strain], µ [minor strain], σ [minor strain], µ [displacement], and σ [displacement]). Most measurement random errors are below 6%. This is several folds smaller in magnitude than the difference in the mean response between the clusters. Several Cutometer® parameters also showed good agreement with µ (displacement). CONCLUSIONS: DIC was able to differentiate skins of different mechanical qualities. We also proposed the physical significance of the DIC metrics. Some of the DIC metrics potentially offer new insights into skin mechanical properties that complement those revealed by conventional instruments. Accurate measurements, large measurement areas along with ease of direct visualization are substantial advantages of DIC.

Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761).

The objective of the present study was to characterize the action of Ginkgo biloba extract (EGb761) and its sub-fractions on glutathione homeostasis in a human keratinocyte cell culture model. Cells were incubated with EGb761, its purified flavonoid (quercetin, kaempferol, rutin) or terpenoids (gingkolides A, B, C, J, bilobalide) constituents or the vehicle for up to 72 hours. Incubation of keratinocytes with the purified flavonoids or terpenoids did not affect cellular GSH levels. However, EGb761 treatment (up to 200 microg/ml) resulted in a dose-dependent increase of cellular GSH. Western blot analysis of extracts from cells treated with EGb761 revealed increased levels of the catalytic subunit of gamma-glutamylcysteinyl synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis. The abundance of mRNA for the catalytic subunit (assayed by RT-PCR) was also increased by the treatment with EGb761. Increased levels of cellular GSH by EGb761 were also observed in other cell lines including those from human bladder and liver as well as in murine macrophages indicating that the induction of gamma-GCS mRNA, protein and GSH may be an ubiquitous effect of EGb761 in mammalian cells.

Role of vitamins in skin care.

Therapeutic (vitamins A and D, and their analogs) and antioxidant (vitamins C, E, and coenzyme Q) vitamins play an increasing role in skin care. Their benefits range from skin conditions such as acne and psoriasis to the protection against environmental insults.

[Percutaneous angioplasty of the infra-renal aorta. Report of 9 cases]. / Angioplastie endoluminale de l'aorte abdominale sous-rénale. A propos de 9 cas.

Between June 1996 and September 2000, nine angioplasties of the infra-renal aorta were performed in two Surgical Vascular Centers (Hospital Saint-Joseph, Paris, Polyclinic La Baule), in 6 men and three women age ranged from 36 to 72 years (middle age 48 years and 2 months). Eight of these patients presented important stenoses of the middle infra-renal aorta, or in the aortic bifurcation, one of them presented an occlusion, leading to severe intermittent claudication, and rest pain. After endoluminal kissing balloon angioplasty, five aortic stents (five patients), and six iliac primitive arteries stents (in three patients), extended beyond the aorta, were placed. One isolated angioplasty was also performed. All the procedures were performed in the operative room, with good results, except for one patient requiring emergency aorto-bi-femoral by-pass, because of acute leg ischemia, immediately following the procedure. Follow-up was clinical, with Us-Doppler scan, and angiogram in all cases. After 36 months follow-up (4-52), all patients are asymptomatic, with permeable stents. This technique is well-known since 1980, without excessive morbidity. Aortic angioplasty represents the right technique, with good long-term results, for middle or terminal aorta atheromatous stenosis, according to classical aorto-bi-femoral by-passes. Final result depends on associated iliac arteries stenoses.

[Critical ischemia of the leg. A technique for distal anastomosis in a a small caliber artery]. / Ischémie critique des membres inférieurs. Un artifice pour anastomose distale sur artère de petit calibre.

CRITICAL ISCHEMIA OF THE LOWER LIMBS: This type of lesion, which spontaneously progresses to gangrene and amputation, is encountered more and more frequently. Emergency endoluminal revascularization or bypass surgery is required. When conventional endoluminal techniques cannot be used, a distal graft using the autologous saphenous vein is a promising alternative to achieve patent vascularization and salvage the limb. IF VENOUS MATERIAL IS NOT AVAILABLE: Usable venous material is not always available due to varicosities, thrombus formation, small size or previous surgery (stripping, coronary surgery, prior revascularization procedure); rates reported range from 20 to 40%. For such patients, other veins (external saphenous, arm veins, superficial femoral veins) may be useful but are not always appropriate for distal repair. Different prostheses might also be used but again do not always provide improved permeability. Most teams however use a polytetrafluoroethylene stent for revascularization of the distal leg. Different technical improvements favor success of prosthetic bypasses, but when used below the knee, flow remains less satisfactory than with venous bypasses. VEIN CUFFS: This procedure is a common adjuvant technique positioning a venous cuff between the recipient artery and the prosthesis. The cuff avoids the direct contact between the prosthesis and the fragile artery that is often difficult to suture. RESULTS: Several series have demonstrated that the rate of success of vein cuff procedures remains lower than venous bypass procedures, but also that flow is better than with simple femorotibial prostheses. PATHOGENIC HYPOTHESES: The reduction of the neo-intimal hyperplasia observed in experimental models is insufficient to explain entirely the observed in vivo benefit. The fact that the suture is easier to make is one possible reason. Indeed the rate of failure of simple prosthetic bypass surgery is high in the immediate postoperative period. These cases of thrombosis result from technical insufficiencies and are undoubtedly overcome by the use of the venous cuff.

Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes.

Benzoyl peroxide (BP) is used as a topical treatment for acne. Besides its anti-bacterial activity, the exact molecular mechanisms underlying its mode of action are not fully understood. In the current study, the effects of BP on cell viability, antioxidant status and, IL-1 and IL-8 gene expression were investigated in HaCaT keratinocytes. Keratinocytes incubated for 24 h with BP exhibited a dose-dependent cytotoxicity at concentrations above 250 microM. Furthermore, in the presence of 300 microM BP about 50% of the cellular vitamin E was depleted within the first 30 min. The intracellular ratio of oxidized to reduced glutathione (GSSG/GSH) was increased significantly starting 6 h after BP treatments indicating that BP reacts rapidly with targets in the cell membrane and more slowly with those in the cytosol. NF-kappaB transactivation was not significantly affected by BP. However, BP treatment of HaCaT keratinocytes resulted in a dose-dependent increase in IL-1alpha gene expression whereas no changes in IL-8 mRNA levels were observed. These results demonstrate that BP induces an inflammatory reaction mediated by oxidative stress by a pathway independent of the redox-sensitive transcription factor NF-kappaB.

Interaction between cultured endothelial cells and macrophages: in vitro model for studying flavonoids in redox-dependent gene expression.

This article focused on two methods to measure the activity of NF-kB. Both methods evalute "post-IkB phosphorylation" stages in the NF-kB activation cascade. In fact, EMSA performed with nuclear extracts provides an information only on NF-kB nuclear translocation and its ability to bind kB-DNA sequences. Likewise, the reporter gene assay is limited to assessing NF-kB-dependent gene expression no matter the mechanism that originally activated NF-kB. Nevertheless, the latter assay represents a more physiological and more reproducible way of measuring NF-kB activity in mammalian cells than the EMSA does. In order to obtain further insights into NF-kB signal transduction pathways, investigating IkB degradation and phosphorylation are recommended. The cloning and characterization of IkB kinases provided new testing possibilities based on measure of their activity.

[Blunt force rupture of the thoracic aorta and diaphragm: an unusual association]. / Rupture de l'isthme aortique et de la coupole diaphragmatique droite: une association inhabituelle.

The aim of this study was to report two cases of rupture of the right hemidiaphragm with intra-thoracic liver hernia, associated with a traumatic aortic disruption. These two lesions followed traffic accidents, and were both treated separately. Both patients had a long-term favourable progression. Association of these two lesions is particularly rare: fewer than 50 cases have been previously described in an extensive review of the literature. CT-scan seems to be particularly efficient in diagnosis, even if less efficient than other more specific explorations. The order of surgical management is guided by the physical examination, and especially by abdominal emergency.

Aneurysms of the internal iliac artery: management strategy.

With the widespread use of CT scans, detection and treatment of internal iliac artery aneurysms (IIA) have become more frequent. In the last few years, endovascular repair has been added to the therapeutic arsenal. We reviewed the records of 38 patients treated for 44 IIA between 1987 and 1997 to assess immediate and long-term outcome using various therapeutic methods. Aneurysms were divided into three groups according to the circumstances of treatment. Group I included 25 IIA treated at the same time as abdominal aortic aneurysm (AAA). The morbidity/mortality rate in this group was comparable to that in patients who underwent isolated AAA repair. Group II included 14 IIA treated during follow-up of AAA repair. Most complications in this group were intraoperative. Group III included five isolated IIA not associated with AAA repair. Complications were similar to those in group I. On the basis of this retrospective analysis, we propose a management strategy in which open surgery, endovascular repair, or both are used, depending on the circumstances of treatment.

From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited.

The effect of French maritime pine bark extract (PBE) on the gene expression profile of HaCaT human keratinocytes was studied using high density filter arrays. The expression profile of both control and PBE-treated cells was determined. Interestingly, PBE was shown to downregulate both calgranulin A and B genes which are known to be upregulated in psoriasis and various dermatoses. Thus, PBE could be considered in human dermatoses.

Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract.

The procyanidin-rich French maritime pine bark extract Pycnogenol (PBE) has been investigated for its effect in protecting human skin against solar UV-simulated light-induced erythema. Twenty-one volunteers were given an oral supplementation of Pycnogenol: 1.10 mg/kg body weight (b. wt.)/d for the first 4 weeks and 1.66 mg/kg b. wt./d for the next 4 weeks. The minimal erythema dose (MED) was measured twice before supplementation (baseline MED), once after the first 4 weeks of supplementation, and a last time at the end of the study. The UVR dose necessary to achieve 1 MED was significantly increased during PBE supplementation. Since the activation of the pro-inflammatory and redox-regulated transcription factor NF-kappaB is thought to play a major role in UVR-induced erythema, the effect of PBE was also investigated in the human keratinocyte cell line HaCaT. PBE, added to the cell culture medium, inhibited UVR-induced NF-kappaB-dependent gene expression in a concentration-dependent manner. However, NF-kappaB-DNA-binding activity was not prevented, suggesting that PBE affects the transactivation capacity of NF-kappaB. These data indicate that oral supplementation of PBE reduces erythema in the skin. Inhibition of NF-kappaB-dependent gene expression by PBE possibly contributes to the observed increase in MED.

[Which indications and techniques for lower limb arteriopathy obliterans and proximal aorto-iliac lesions?]. / Artériopathie oblitérante des membres inférieurs et lésions proximales aorto-iliaques: quelles techniques? Quelles indications?

Atherosclerotic aorto iliac occlusive disease are not the most frequent lesions in the lower limbs. Isolated aortic iliac lesions are often associated with intermittent claudication; critical ischemia with proximal aorto iliac lesions can be due to acute occlusion or associated femoropopliteal occlusive lesions. Preoperative explorations need Duplex Scan, Arteriography and CT Scan to define extensive lesions and wall' calcifications. Endovascular procedures are, in this lesion, safe, effective and permit to delay conventional surgery. The best strategy, today, needs to known endovascular procedures and surgical procedures to obtain the most efficient anatomic result.

[Atypical cellular blue nevus. Apropos of 1 case]. / Le naevus bleu cellulaire atypique. A propos d'un cas.

We report a new case of a cellular blue nevus with clinicopathologic atypia. It was a large lesion presenting clinically as a vascular tumor located in the middle of the back. It grew for 2 years without skin ulceration. The pathological study suggested a cellular blue nevus with moderate nuclear atypia, without any atypical mitosis and necrosis. The differential diagnosis such as malignant blue nevus and melanoma are discussed in search of a better definition of these rare lesions.

[Symptomatic treatment of nephrotic syndrome]. / Traitement symptomatique du syndrome néphrotique.

OBJECTIVES OF SYMPTOMATIC TREATMENT: The goal is to maintain quality of life, prevent immediate complications (thromboembolic events, infection, drug reactions), prevent late complications related to atherosclerosis, and limit the progression of the chronic renal failure. THERAPEUTIC ARMAMENTARIUM: Six categories can be described. i) A reduction in proteinuria, essential for controlling the intensity of other manifestations, can be improved with a normal protein content (1 g/kg ideal weight/d) low-salt diet, strict blood pressure control, and most importantly, CEI given alone or in combination with AA2. ii) Restoration of a normal extracellular fluid (edema and high BP) can be achieved by low sodium intake and loop diuretics in fractionated increasing doses (sometimes with combination regimens). It is advisable to keep blood pressure below 125/75 mmHg. iii) Prevention of thromboembolic events (risk level dependent on urine protein output) relies on antivitamin K anticoagulants and low-molecular weight heparins. iv) Adapted prescription of protein-bound drugs. v) Lowering LDL-cholesterol, a risk factor for atherosclerosis, with an adapted diet and HMG CoA inhibitors. vi) Prevention of chronic renal failure. The development and course of chronic renal failure depend not only on the histological glomerular lesion and/or the etiology but also on supplementary glomerular and tubulointerstitial damage directly related to the degree of proteinuria. MORE THAN SYMPTOM RELIEF: Symptomatic treatment of nephrotic syndrome must be considered as an integral part of a rigorous goal-oriented therapeutic strategy.

Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappaB-dependent gene expression in RAW 264.7 macrophages.

Flavonoids are potent antioxidants and have been associated with lowering the risk of cardiovascular diseases. In this study, the effect of flavonoids (monomers, dimers and a trimer) as well as French maritime pine bark extract, Pycnogenol, on NO production, tumor necrosis factor-alpha (TNF-alpha) secretion and nuclear factor (NF)-kappaB activity was compared. Monomers and dimers repressed NO production, TNF-alpha secretion and NF-kappaB-dependent gene expression induced by interferon gamma, whereas the trimeric procyanidin C2 and Pycnogenol enhanced these parameters. In addition, in unstimulated RAW 264.7 macrophages, both procyanidin C2 and Pycnogenol increased TNF-alpha secretion in a concentration- and time-dependent manner. These results demonstrate that procyanidins act as modulators of the immune response in macrophages.

Nitric oxide synthesis and TNF-alpha secretion in RAW 264.7 macrophages: mode of action of a fermented papaya preparation.

Macrophage inducible nitric oxide synthase is able to generate massive amounts of nitric oxide (NO) which contributes to the host immune defense against viruses and bacteria. Monocyte-macrophages stimulated with the bacterial wall component lipopolysaccharide (LPS) and cytokines such as interferon-gamma (IFN-gamma) express the inducible form of nitric oxide synthase (iNOS). Furthermore, tumor necrosis factor-alpha (TNF-alpha) is one of the central regulatory cytokines in macrophage antimicrobial activity and synergizes with IFN-gamma in the induction of NO synthesis. Because of its pivotal role in both antimicrobial and tumoricidal activities of macrophages, a significant effort has focused on developing therapeutic agents that regulate NO production. In the present study fermented papaya preparation (FPP) is shown to exert both immunomodulatory and antioxidant activity in the macrophage cell line RAW 264.7. Interestingly, a low and a high molecular weight fraction (LMF and HMF, respectively) of FPP exhibited different activity patterns. FPP fractions alone did not affect NO production. However in the presence of IFN-gamma, both LMF and HMF significantly increased iNOS activity and nitrite as well as nitrate accumulation. NO radical formation measured in real-time by electron paramagnetic resonance spectroscopy was higher in the presence of LMF and IFN-gamma. On the contrary, iNOS mRNA levels were enhanced further with HMF than with LMF. Moreover, LMF displayed a stronger superoxide anion scavenging activity than HMF. In the presence of IFN-gamma, both FPP fractions stimulated TNF-alpha secretion. However in non-stimulated macrophages, TNF-alpha secretion was enhanced by HMF only. Since water-soluble FPP fractions contained no lipid A, present data indicate that FPP is a macrophage activator which augments nitric oxide synthesis and TNF-alpha secretion independently of lipopolysaccharides.

[Behcet's disease and iatrogenic arterial complications: importance of pre-operative noninvasive explorations]. / Maladie de Behçet et complications artérielles iatrogènes: intérêt des explorations pré-opératoires non invasives.

We report a case of Behçet's disease complicated with a popliteal aneurysm, which appeared 8 years after first etiologic diagnosis. The points of interest of this observation are the pre-operative explorations and particularly the Magnetic Resonance Angiography (RMA). This last seems to be particularly safe for aortic and lower limbs aneurysms explorations, and can be performed without arterial functions. In fact the risk of arteriogram is effective in Behçet's disease with secondary false aneurysms. RMA and US-Doppler scan must be first proposed in Behçet's disease in case of aortic and peripheral aneurysms.

Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells.

NF-kappaB is a potent cellular activator of HIV-1 gene expression. Down-regulation of NF-kappaB activation is known to inhibit HIV replication from the latently infected cells. Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis. We previously reported that gold compounds, especially aurothioglucose (AuTG) containing monovalent gold ion, inhibited the DNA-binding of NF-kappaB in vitro. In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected OM10.1 and Ach2 cells. Tumor necrosis factor (TNF)-alpha-induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by non-cytotoxic doses of AuTG (>10 microM in OM10.1 cells and >25 F.M in Ach2 cells), while 25 microM of the counter-anion thioglucose (TG) or gold compound containing divalent gold ion, HAuCl3, had no effect. The effect of AuTG on NF-kappaB-dependent gene expression was confirmed by a transient CAT assay. Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells, supporting our previous hypothesis that gold ions could block NF-kappaB-DNA binding by a redox mechanism. These observations indicate that the monovalent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV.