How long does the volumizing effect of a Zingiber officinale-based lip plumper last?

OBJECTIVE: Lip plumpers should enhance lip volume. It has been shown that no noticeable result was obtained after long term use of these products. The present study has been carried out to assess lip plumpers' short term effectiveness within 2 h from application. METHODS: Effectiveness was assessed using non-invasive techniques. The effect on vascularisation was analyzed with the Mexameter MX 16® , and the volume enhancing effect was assessed by anthropometric measures and profilometry analysis from 3D scanning electron microscope (SEM) images using Alicona's MEX software. Sixty female volunteers were recruited for the study and the measurements were taken 15, 30, 60, 90 and 120 min after product application. RESULTS: Product application produced a statistically significant increase of lip vascularisation during the first 15 min, which stayed unchanged until the 30th min, then decreased in intensity. The volumizing effect was revealed by 3D profilometry analysis only, not by anthropological measurements. The use of 3D SEM images showed an increase of 0.50 mm in the protrusion of the lip vermilion (MHP parameter) during the first 15 min from product application. CONCLUSION: Results suggest that the lip plumper temporarily enhances vasodilation and increases lip volume.

Atlas occipitalisation associated with other anomalies in a 16th century skeleton from Sardinia (Italy).

Archaeological excavations carried out in the plague cemetery of 16th century Alghero (Sardinia) brought to light the skeleton of a male aged 35-45 years, showing anomalies of the atlas. A macroscopic and radiological study has been carried out. The first cervical vertebra is fused with the skull base, resulting in an occipitalisation of the atlas. Absence of the costal element of the left foramen transversarium, resulting in an open anterior foramen transversarium, and posterior arch defect are also observed. The atlanto-occipital junction is a complex structure, susceptible to develop different patterns of congenital defects. These anatomical variations of atlas should be considered in modern clinical practice in order to formulate a correct diagnosis and to conceive an appropriate treatment. Osteoarchaeological cases are important as, beside to ascertain the presence of congenital defects in past populations, allow an in-depth study in dry bones, which can help modern medicine in interpreting anatomical variations. We present an association of congenital anomalies of the atlanto-occipital junction, a condition rarely documented in ancient and modern human skeletal remains.

From microvasculature to fibroblasts: Contribution of anti-endothelial cell antibodies in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis, caused by microvascular dysfunction. In recent years, the hypothesis that anti-endothelial cell antibodies (AECA) play a key role in microvascular damage seems to be increasingly convincing. In fact, AECA can induce antibody-dependent cellular apoptosis and stimulate the microvasculature to release pro-inflammatory and pro-fibrotic cytokines. Human-microvascular-endothelial-cells (MVECs) were stimulated with SSc sera (with and without AECA) and with sera from healthy donors. The conditioned MVEC culture media were then added to fibroblast cultures obtained from control skin (CTR), non-affected skin of SSc patients (NA), and affected skin of the same sclerodermic (SSc) patients, respectively. AECA contributed to the MVEC increased release of endothelin-1 (ET-1) in the culture medium and to MVEC apoptosis. Fibroblast (CTR, NA, and SSc) proliferation was increased after treatment with AECA-positive conditioned media, compared to AECA-negative and control conditioned media. Furthermore, both AECA-positive (in major contribution) and AECA-negative conditioned media were responsible for alpha-smooth-muscle-actin (αSMA) over-expression in all fibroblast cultures, compared to control conditioned media. Fibroblast type I collagen synthesis was upregulated by both SSc conditioned media (with and without AECA). Finally, the synthesis of fibroblast transforming-growth-factor-beta (TGF-ß) was statistically higher in AECA-positive conditioned media, compared to AECA-negative and control conditioned media. These findings support the concept that AECA may mediate the crosstalk between endothelial damage and dermal-fibroblast activation in SSc.

The localization of the distal perforators of posterior tibial artery: a cadaveric study for the correct planning of medial adipofascial flaps.

PURPOSE: The adipofascial flap, introduced by Lin in 1994, has many advantages compared to fasciocutaneous or free flaps. Its dissection is relatively easy and fast with low donor-site morbidity, and it does not alter the shape of the leg. The aim of this dissection study is to evaluate the anatomic localization of the most distal perforator of the posterior tibial vessels to provide an anatomical rationale for the safe harvesting of distally based medial adipofascial flaps of the leg. MATERIALS AND METHODS: 30 Lower limbs from 15 cadavers were used for this study. The most distal perforator from posterior tibial perforator artery, accompanied by at least one vein, was identified and its distance from the medial malleolus was noted. RESULTS: A distal perforator was found in all specimens; the mean caliber was 0.77 mm. In all cases, the perforator artery passed in the septum between flexor hallucis longus m. and flexor digitorum longus m. and was accompanied by two veins. In our series, the distance between the lowest perforator and the medial malleolus ranged from 3.5 to 8.2 cm. The median was 6.75 cm, the 5th percentile 4 cm and the 95th percentile 8.1 cm. The mean distance of the perforator from the medial tibial border was 1.23 cm. The mean ratio between the distance of perforator from the medial malleolus and the total leg length was 21%. CONCLUSION: Compared to all previous researches, our study has found more distal perforators from posterior tibial perforator artery. This fact may have important clinical consequences, because the anteromedial adipofascial flap would cover more distal soft tissue defects. Moreover, our data suggest some safety parameters to make the rising of a medial adipofascial leg flap safer in surgical practice.

Is osteopontin involved in cutaneous fibroblast activation? Its hypothetical role in scleroderma pathogenesis.

Osteopontin (OPN) is an extracellular matrix protein implicated in bone remodeling, but it presents also pro-inflammatory and pro-fibrotic properties. OPN expression also occurs upon exposure of cells to classical mediators of acute inflammation such as tumor necrosis growth factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), as well as fibrogenic cytokines such as transforming growth factor beta (TGF-beta), although a detailed understanding of these regulatory pathways is still unknown. Plasma OPN levels in both limited and diffuse systemic sclerosis patients (lSSc and dSSc) were statistically higher compared to those of control subjects. Immunohistology demonstrated that high TGF-beta levels, alpha smooth muscle actin (alphaSMA) levels and consequently high OPN levels were found in the affected skin of sclerodermic patients (lSSc and dSSc) compared to levels found in healthy skin. In order to better understand how OPN interferes with the fibrotic process, healthy skin fibroblasts were treated for 24 and 48 hours with bleomycin and with endothelin-1 (ET-1) plus TGF-beta in order to induce the fibrogenesis. After 48 hours of stimulation, healthy treated fibroblasts showed statistically increased alphaSMA levels (index of differentiation into myofibroblasts) and simultaneously statistically increased OPN levels compared to healthy untreated ones. This study demonstrates that OPN levels increase simultaneously with the increasing of alphaSMA levels, therefore it is reasonable to hypothesize that OPN interferes in the pathogenesis of Systemic Sclerosis in the early stage of fibroblast differentiation process.

A new contrast agent for radiological and dissection studies of the arterial network of anatomic specimens.

PURPOSE: The aim of the present study is to propose a new contrast agent that can be easily applied both to CT and dissection studies to replace lead oxide based formulas for comparative anatomical analyses of the vascularisation of cadaveric specimens. METHODS: The infusion material was an epoxy resin, especially modified by the addition of barium sulphate to enhance its radiopacity. The final copolymer was toxicologically safe. To test the properties of the new material, several cadaveric limb injections were performed. The injected specimens were both CT scanned to perform 3D vascular reconstructions and dissected by anatomical planes. RESULTS: There was a perfect correspondence between the image studies and the dissections: even the smallest arteries on CT scan can be identified on the specimen and vice versa. The properties of the epoxy allowed an easy dissection of the vessels. CONCLUSIONS: The new imaging techniques available today, such as CT scan, can evaluate the vascular anatomy in high detail and 3D. This new contrast agent may help realising detailed vascular studies comparing CT scan results with anatomical dissections. Moreover, it may be useful for teaching surgical skills in the field of plastic surgery.

Pallister-Killian syndrome in a preterm newborn who died soon after precipitous delivery: cytogenetic analysis.

The authors report a preterm neonate with dysmorphic traits and cleft palate who was born preterm because of precipitous delivery and died soon after birth notwithstanding neonatal intensive care unit (NICU) support. The cytogenetic analysis on fibroblasts from post-mortem skin biopsy demonstrated a Pallister-Killian syndrome (PKS). PKS is a cytogenetically syndrome characterized by a tissue limited mosaic distribution of one isochromosome 12p (tetrasomy 12p). Clinical manifestations of PKS are variable, and some symptoms may overlap with other malformative syndromes, thus the correct diagnosis mainly depends on the demonstration of the specific cytogenetic abnormality.

Macitentan slows down the dermal fibrotic process in systemic sclerosis: in vitro findings.

Systemic sclerosis (or scleroderma) is an autoimmune disease characterized by skin and internal organ fibrosis, caused by microvascular dysfunction. The microvascular damage seems to be a consequence of an endothelial autoimmune response, followed by activation of the inflammatory cascade and massive deposition of collagen. Endothelin-1 (ET-1) contributes to the inflammatory and fibrotic processes by increasing the concentration of pro-inflammatory and pro-fibrotic cytokines, and it is considered one of the most relevant mediators of vascular damage in scleroderma. It is indeed found in very high concentration in serum of sclerodermic patients. Moreover, in these pathological conditions there is an increased expression of ET-1 receptors (ETA and ETB), which mediate the detrimental action of ET-1, and often a change of ETA/ETB ratio. The aim of the present study is to evaluate the in vitro effect of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist, and its major metabolite (ACT-132577) on alpha smooth muscle actin (alphaSMA) expression, evaluated on dermal fibroblasts from healthy subjects and on dermal fibroblasts from lesional and non-lesional skin from sclerodermic patients. The combination of macitentan and its major metabolite reduced the levels of αSMA after 48 h in sclerodermic fibroblasts from lesional skin. No relevant changes in αSMA levels were found in fibroblasts from non-lesional skin, whose behavior is similar to that of dermal fibroblasts from healthy patients.

Unbalanced 1q whole-arm translocation resulting in der(14)t(1;14)(q11-12;p11) in myelodysplastic syndrome.

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.

Expression of RXFP1 in skin of scleroderma patients and control subjects.

OBJECTIVES: Relaxin (RLX) is involved in extracellular matrix and collagen remodelling. The therapeutic role of the circulating isoform RLX-2 as an anti-fibrotic factor in systemic sclerosis (SSc) has been investigated. Several RLX family peptide receptors (RXFPs) are recognized in humans: RLX-2 is a ligand for RXFP1/LGR7 and RXFP2/LGR8. The aim of this study was to define the pattern of expression of LGR7 in different types of human skin cells and to compare normal skin with lesional and unaffected skin from patients with limited SSc (lSSc). METHOD: We analysed RXFP1 immunolocalization on skin biopsies and cultured fibroblasts from lSSc patients and control subjects. Western blot analysis was carried out on fibroblast lysates. RESULTS: RXFP1 showed cytoplasmic localization on skin cells from control subjects and non-lesional skin from lSSc patients: keratinocytes, gland epithelial cells, endothelium, smooth muscle cells, and fibroblasts. Immunogold electron microscopy confirmed a diffuse epithelial cytoplasmic localization of RXFP1. A substantially lower RXFP1 expression was observed in scleroderma skin, with a lack of staining in most cells. Occasional weak reactivity was observed in cultured scleroderma fibroblasts, while control fibroblasts showed a diffuse cytoplasmic immunoreactivity of RXFP1, confirmed by Western blot analysis. CONCLUSIONS: The decreased cellular expression of RLX-2 receptor RXFP1 in scleroderma skin might represent a pro-fibrotic factor and contribute to the substantial inefficacy of RLX treatment in SSc, as reported in the literature. The pathophysiology of the decrease in RXFP1 may be linked to high RLX-2 serum levels previously detected in SSc, but it has yet to be elucidated.

Serum proteome of patients with systemic sclerosis: molecular analysis of expression and prevalence of haptoglobin alpha chain isoforms.

Haptoglobin (Hpt) is an acute phase protein characterized by three major phenotypes (Hpt 1-1, Hpt 2-1 and Hpt 2-2). The Hpt 2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, the Hpt 2-2 phenotype induces a shift from Th1 to Th2 response and increases fibrotic processes. On this basis, we performed serum proteomic analysis of patients with Systemic Sclerosis (SSc), a connective tissue disorder associated with Th2-type immune response and characterized by interstitial and perivascular fibrosis due to different factors (including genetic, environmental, immunological and microchimeric factors). Serum of 23 SSc outpatients patients (4 males, 19 females, mean age 54+-5.3 years) diagnosed according to the American Rheumatism Association (ARA) criteria, were considered for the proteomic analysis and compared to serum of 21 control subjects. Serum depleted of HAP was analyzed by 2-DE, and Hpt chain spots were identified by WB. The expression frequency of each Hpt α chain in SSc patients and controls was compared and quantitative analysis of spot expression (percent Vol) was performed. Above all,, our study amplifies the limited data in the literature on proteomic analysis in SSc, also confirming previous data that revealed a significant increase of haptoglobin type 2-2 and a concomitant decrease of the 1-1 phenotype in SSc patients. Moreover, our results demonstrate that c spots are more prevalent in SSc patients than in controls (91.3% vs 55.5%, p<0.05), while the expression frequency of a and b spots does not change. In patients Hpt 2-1 or Hpt 1-1 e spot is less abundant. According to our results, the c and e spots can be considered markers for SSc and thus be of use for the early diagnosis of connective tissue disorders and in establishing appropriate treatment.

Bosentan treatment for Raynauds phenomenon and skin fibrosis in patients with Systemic Sclerosis and pulmonary arterial hypertension: an open-label, observational, retrospective study.

Raynaud?s phenomenon (RP) and cutaneous fibrosis are the distinctive manifestations of scleroderma, in which Endothelin-1 plays a fundamental pathogenetic role. Bosentan, an Endothelin-1 receptor antagonist used for the treatment of pulmonary arterial hypertension, retards the beginning of new sclerodermic digital ulcers (DU). This open-label, observational, retrospective study verified the effect of Bosentan on RP and skin fibrosis in sclerodermic outpatients affected by pulmonary arterial hypertension without DU. Fourteen subjects (13 women, 1 man; mean age 60 ± 7.5 years; ten with limited and four with diffuse scleroderma) were observed at baseline (T0) and after four (T1), twelve (T2), twenty-four (T3) and forty-eight (T4) weeks during treatment with Bosentan. They were evaluated for daily quantity and duration of RP attacks and skin thickness (using modified Rodnan total skin score, MRSS). Videocapillaroscopic evaluation was performed at T0 and T4. Bosentan decreased significantly the number and duration of RP attacks, beginning at T2 (p<0.05). Videocapillaroscopy showed significant improvement of microcirculatory patterns at T4 (p<0.05). MRSS decreased throughout the study, reaching the statistical significance at T3 and T4 (p<0.01) in the whole cohort. The present data suggest that Bosentan is effective in stabilizing the microcirculation involvement and in improving skin fibrosis irrespective of scleroderma patterns.

Low cadmium concentration in whole blood from residents of northern Sardinia (Italy) with special reference to smoking habits.

INTRODUCTION: The present study was initiated to investigate the cadmium concentrations in whole blood of Northern Sardinian, non-occupationally exposed adult subjects. Sardinia is a large Italian island which differs genetically and environmentally from other mainland Italian areas. METHODS: Two hundred and forty-three adults (157 females and 86 males) were selected in the study area from subjects who were undergoing blood collection for laboratory analysis during the period January 2005-May 2005. Whole blood was analysed by graphite furnace atomic absorption spectrometer equipped with a Zeeman-effect background corrector (Perkin Elmer ZLS5100) and an auto sampler. The adopted analytical procedure uses the Stabilized Platform Temperature Furnace (STPF) technique. RESULTS: The mean value of Blood Cadmium Concentration (BCdC), expressed as Geometric Mean, was 0.32 pg/l (CI 95%: 0.31-0.34 l) in non-smokers to 034 pg/l (CI 95%: 0.30-0.39 pg/l) in ex-smokers up to 0.47 gg/ll(CI 95%: 0.42-0.53 pg/l) in smokers (p < 0.0001). DISCUSSION: The results show that BCdC levels in Northern Sardinian non-occupationally exposed adults are lower than levels found in many other regions, including those within Italy. Nevertheless, similar values have been detected in other European countries and cities. CONCLUSIONS: In relation to other reports in which data were analysed by strata for smoking habit and age, we found similar BCdC values among non smokers. However, Sardinian smokers seem to show lower levels of blood cadmium.

High bone turnover is associated with accelerated bone loss but not with increased fracture risk in men aged 50 and over: the prospective MINOS study.

OBJECTIVES: The association of bone turnover markers (BTM) with bone loss and fracture risk in men is poorly studied. The morphological basis of such a relationship is unknown. The objective of this study was to evaluate the association between baseline BTM levels and subsequent bone loss and fracture risk in men. METHODS: This study is a prospective 7.5-year follow-up of the cohort composed of 723 men aged 50-85 years. Serum concentrations of osteocalcin, bone alkaline phosphatase (BAP), procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen (beta-CTX-I) and urinary excretion of deoxypyridinoline and beta-CTX-I were measured at baseline. Every 18 months, incident fractures were recorded and bone mineral density (BMD) was measured by dual energy x ray absorptiometry DXA (spine, hip, distal forearm, whole body). RESULTS: Increase in BTM levels was associated with faster bone loss at the level of the trochanter, whole body and distal forearm. At the level of the distal radius and the ulna, increase in the serum BAP and beta-CTX-I levels were associated with faster apparent, net and estimated endosteal bone mineral loss. BTM levels did not correlate with the periosteal expansion rate. BTMs were significantly associated with bone mineral loss but their predictive power was poor. BTMs did not predict incident fractures. CONCLUSIONS: In men aged 50 and over, accelerated bone turnover is associated with greater endosteal bone mineral loss. From a practical point of view, BTMs cannot be used for the prediction of accelerated bone loss or fractures in the clinical management of osteoporosis in men.

Cytomorphologic and ultrastructural study of nasal mucosa by means of brushing: a comparison between asymptomatic and rhinitic subjects.

The authors compared the cytomorphologic and ultrastructural features of nasal epithelium collected by means of brushing from asymptomatic subjects with these of patients affected by nasal polyposis (NP), allergic (AR) and non-allergic rhinitis (NAR). A brushing of nasal epithelium was taken from each member of both groups, and analysed under light and electron microscopy. The observation showed normal ciliary patterns and preserved intercellular joints in the great majority of asymptomatic subjects, while in all subjects of the pathologic group the junctions appeared variously damaged or absents, with ciliary abnormalities. The damage to the intercellular joints, rather than the alterations of ciliary patterns, seemed to represent in this study the border between the absence of symptoms and the presence of chronic inflammation. Therefore, a reduced tightness of the intercellular joints could contribute to the impairment of the mucociliary clearance, priming the vicious circle that leads to the condition of chronic inflammation.

An experimental study of the effect of ischemia on testicular structure in the rat. Efficacy of intravenous inosine.

The damages caused by experimental testicular ischemia lasting 60 minutes have been examined in the rat. The histologic alterations of the germinal epithelium and of the tunica propria are studied, using semi-thin sections stained with 1% toluidine blue. The results show that a testicular ischemia of 60 minutes causes damages to the testicular structures. These damages cannot be prevented or avoided by either surface cooling or cold perfusion; however, intravenous inosine prior to ischemia has a protective effect.

Inner ear pressure changes modify ADH secretion in freely moving guinea pig.

The present study was designed to elucidate the relationship between endolymphatic pressure and plasma ADH levels in conscious guinea pigs. Plasma ADH (pADH) was measured in basal conditions and after having applied positive or negative pressure of 20 cmH2O to the inner ear. The experimental protocol was designed to avoid any interference on ADH release caused by anesthesia and surgical stress. There was no change in blood pressure, heart rate, plasma Na (pNa) and osmolality (pOsm) after inner ear pressure (IEP) modifications. However, pADH was inversely related with IEP: pADH averaged 31.4 +/- 7.0 pg/ml (mean +/- S.D.) in basal conditions, rising to 48.8 +/- 19.3 when IEP was lowered and falling to 16.6 +/- 10.3 when IEP was raised. These results confirm that structures in the inner ear help control of ADH release.

Histogenesis and morphology of the flexor tendon pulley system in the human embryonic hand.

The number, position, structural and ultrastructural features of the flexor tendon pulley system in six human embryonic hands, aged from 6 to 12 weeks, were studied by light and electron microscope. The pulley system can be recognized from the ninth week; later, at 12 weeks, the structures are easily identified around the flexor tendon in positions closely correlated to those found during post-natal growth and in the adult hand. Structurally and ultrastructurally the pulleys are not simply thickened portions of the sheath. They are formed by three layers: an inner layer, one or two cells thick, probably representing a parietal synovial tendon sheath; a middle layer formed by collagen bundles and fibroblasts whose direction is mainly perpendicular to the underlying phalanx; and an outermost layer consisting of mesenchymal tissue with numerous vessels which extends dorsally in an identical layer, forming a ring that includes flexor and extensor tendons and the cartilaginous model of the phalanx. The pulley does not have a semicircular shape but a much more complicated one, owing to the middle layer which in part runs dorsally and in part ventrally, under the flexor tendons.