The Importance of Dermatoscopy for the Diagnosis of Melanonychia.

Melanonychia is the brown or black color of the finger or toe nail due to melanin deposition or melanocytes in the nail plate. The evidence of melanocytic disease is made by the dermatoscope, which allows to highlight the anomalies of the plate. The purpose of our study was to evaluate dermatoscopically the melanonychia, both in the form of stain and longitudinal on finger and/or toe nails in order to establish the type of nail hyperpigmentation. MATERIALS AND METHOD: 33 patients with longitudinal and stain melanonychia were examined with 30x Molemax HD computerized dermatoscope between May 2017-septembre 2018 in this prospective study conducted in the Department of Dermatology of Medical Center Dr. Ianosi (Craiova, Romania). Clinical data included: type of melanonychia, number and name of involved fingers, the presence or absence of fungal infections, nail apparatus tumors or hemorrhage. RESULTS: The most frequent nail diagnosis was fungal infection (onychomycosis) observed in 18 patients (54.54%), malignant melanoma was diagnosed in 1 patient (3.03%) and the junctional nevus in 4 patients (12.12%). In 18 patients which has longitudinal melanonychia, the most frequent involved finger was the big toe, and in 15 patients which has stain melanonychia, all of them (100%) had affected the big toe, 7 (46.66%) patients had affected the thumb and the same percent the forth finger. CONCLUSION: Nail dermatoscopy is an important method in establishing the diagnosis of melanonychia and allowed to avoid unnecessary biopsy for melanonychia.

The Importance of Dermoscopy in Early Recognition of Melanoma in Situ.

Early recognition of melanoma in situ (MIS) is an ongoing challenge in dermatology. It rarely arises 'de novo', most frequently resulting due to the transformation of an atypical nevus. The diagnostic criteria for MIS are diverse dermoscopy being the most used and it has a sensitivity of 83% and a specificity of 69% in detecting melanomas. The main objective of our study was to establish the sensitivity and the specificity of each of the 7-point checklist criteria used to differentiate melanocytic nevi from in situ malignant melanoma. The study group included 200 patients, aged over 18 years, with atypical pigmentary nevi after clinical aspects that presented changes in clinical appearance (shape, color, dimensions) during the last 6 months. On each patient we used the 7-point checklist of Argenziano (C1-C7). The study was performed at the Medical Center Dr. Ianosi, in Craiova between January 2016 and September 2018 and it was used Molemax HD computerized dermatoscope. The C1÷C3 criteria are significantly relevant in establishing the diagnosis of MIS in comparison with the diagnosis of nevus, unlike the C4-C7 criterion that is not definitely relevant for confirmation of the MIS diagnosis. There are no enough specific dermoscopic criteria to differentiate MIS from atypical nevus.

Treatment of Lower Limbs Telangiectasias with Nd: Yag Laser-Prospective Study on 446 Patients.

In the last two decades Nd: YAG laser has become a standard of treatment of telangiectasias of the lower limbs in C1EAP stage of chronic venous insufficiency. This paper shows the results of a two years study period of telangiectasias of lower limbs with Nd: YAG laser conducted in a specialised centre in this type of procedures. The study group consisted of 446 patients (21 males and 425 females) with telangiectasias (C1EAP) on the lower limbs between January 2016-December 2017. The patients had to complete a form in which they noted the initial state on a scale from 1 to 10 but also the result of the treatment and the intensity of the pain during the laser treatment. Moreover, the doctor also evaluated the results of the treatment for each and every patient taking also into account the initial phase of the disease. We observed a significant improvement of the clinical appearance (the reduction of telangiectasias) almost in the entire study group, regardless of the gender and the age, but the intensity of the pain was higher in men and in persons under the age of 30. Based on these data we can conclude that Nd: YAG laser represents a minimally invasive therapeutic option with minor side effects and major aesthetic results and furthermore it can be combined with several other methods (microsclerotherapy, radiofrequency, complex surgery) in order to improve peripheral chronic venous insufficiency.

Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts.

In the pathogenesis of dilated cardiomyopathy, cytoskeletal proteins play an important role. In this study, we analyzed titin expression in left ventricles of 19 control human donors and 9 severely diseased (nonischemic) dilated cardiomyopathy (DCM) transplant-patients, using gel-electrophoresis, immunoblotting, and quantitative RT-PCR. Both human-heart groups coexpressed smaller (approximately 3 MDa) N2B-isoform and longer (3.20 to 3.35 MDa) N2BA-isoforms, but the average N2BA:N2B-protein ratio was shifted from approximately 30:70 in controls to 42:58 in DCM hearts, due mainly to increased expression of N2BA-isoforms >3.30 MDa. Titin per unit tissue was decreased in some DCM hearts. The titin-binding protein obscurin also underwent isoform-shifting in DCM. Quantitative RT-PCR revealed a 47% reduction in total-titin mRNA levels in DCM compared with control hearts, but no differences in N2B, all-N2BA, and individual-N2BA transcripts. The reduction in total-titin transcripts followed from a decreased area occupied by myocytes and increased connective tissue in DCM hearts, as detected by histological analysis. Force measurements on isolated cardiomyofibrils showed that sarcomeric passive tension was reduced on average by 25% to 30% in DCM, a reduction readily predictable with a model of wormlike-chain titin elasticity. Passive-tension measurements on human-heart fiber bundles, before and after titin proteolysis, revealed a much-reduced relative contribution of titin to total passive stiffness in DCM. Results suggested that the titin-isoform shift in DCM depresses the proportion of titin-based stiffness by approximately 10%. We conclude that a lower-than-normal proportion of titin-based stiffness in end-stage failing hearts results partly from loss of titin and increased fibrosis, partly from titin-isoform shift. The titin-isoform shift may be beneficial for myocardial diastolic function, but could impair the contractile performance in systole.

Alcohol affects the skeletal muscle proteins, titin and nebulin in male and female rats.

Alcoholic myopathy is characterized by decreased protein synthesis and contents resulting in atrophy of muscle fibers. We investigated the effect of alcohol on the cytoskeletal muscle proteins, nebulin and titin. Because women are more susceptible than men to the toxic effects of alcohol, male and female rats were included. Four groups were investigated: alcoholic males, pair-fed males, alcoholic females, pair-fed females. Alcohol consumption per unit body weight was 12.9 g/kg.d, with no difference between males and females. After 10 wk, male and female rats fed alcohol had lower gastrocnemius and plantaris protein and RNA contents (P < 0.001), with no effect on soleus, indicating myopathy of type II fibers. The gastrocnemius was fractionated to measure myofibrillary protein contents. Low percentage SDS-gel electrophoresis was performed to determine myosin heavy chain (MHC), nebulin and titin contents. Alcohol reduced gastrocnemius myofibrillary protein and MHC contents, and the plantaris RNA/protein ratio (P < 0.01). The titin/MHC and nebulin/MHC ratios were unaffected, suggesting a concomitant reduction in titin and nebulin. The decreases in titin and nebulin contents may affect muscle function. An interaction between gender and alcohol was noted for the plantaris RNA/protein ratio (P < 0.025), suggesting a reduced capacity for muscle protein synthesis in females.

Passive stiffness changes in soleus muscles from desmin knockout mice are not due to titin modifications.

Passive stiffness was found to be increased in mouse soleus muscles lacking desmin. Because titin is considered to be the major source of muscle elasticity, the stiffening might be explainable by titin adaptation. To test this, passive mechanical properties of single skinned fibres of soleus muscles from desmin knockout and control mice were analysed by using various extension tests. Titin expression was studied by SDS-gel electrophoresis. Absence of desmin did not modify either electrophoretic mobility of the titin band (3700 kDa) or optical density-unit ratios between bands for titin and nebulin (congruent with 0.3) and bands for titin and myosin heavy chain (congruent with 0.08). Elastic properties of fibres were not altered in the absence of desmin since passive tensions were similar under quasi-static (56-66 kN m(-2)) and dynamic (100-118 kN m(-2)) conditions whatever the kind of fibre. Thus, titin is unlikely to be responsible for the large increase in passive stiffness observed in whole soleus muscles when desmin is lacking.

Interaction between PEVK-titin and actin filaments: origin of a viscous force component in cardiac myofibrils.

The giant muscle protein titin contains a unique sequence, the PEVK domain, the elastic properties of which contribute to the mechanical behavior of relaxed cardiomyocytes. Here, human N2-B-cardiac PEVK was expressed in Escherichia coli and tested-along with recombinant cardiac titin constructs containing immunoglobulin-like or fibronectin-like domains-for a possible interaction with actin filaments. In the actomyosin in vitro motility assay, only the PEVK construct inhibited actin filament sliding over myosin. The slowdown occurred in a concentration-dependent manner and was accompanied by an increase in the number of stationary actin filaments. High [Ca(2+)] reversed the PEVK effect. PEVK concentrations >/=10 microgram/mL caused actin bundling. Actin-PEVK association was found also in actin fluorescence binding assays without myosin at physiological ionic strength. In cosedimentation assays, PEVK-titin interacted weakly with actin at 0 degrees C, but more strongly at 30 degrees C, suggesting involvement of hydrophobic interactions. To probe the interaction in a more physiological environment, nonactivated cardiac myofibrils were stretched quickly, and force was measured during the subsequent hold period. The observed force decline could be fit with a three-order exponential-decay function, which revealed an initial rapid-decay component (time constant, 4 to 5 ms) making up 30% to 50% of the whole decay amplitude. The rapid, viscous decay component, but not the slower decay components, decreased greatly and immediately on actin extraction with Ca(2+)-independent gelsolin fragment, both at physiological sarcomere lengths and beyond actin-myosin overlap. Steady-state passive force dropped only after longer exposure to gelsolin. We conclude that interaction between PEVK-titin and actin occurs in the sarcomere and may cause viscous drag during diastolic stretch of cardiac myofibrils. The interaction could also oppose shortening during contraction.

Kettin, a major source of myofibrillar stiffness in Drosophila indirect flight muscle.

Kettin is a high molecular mass protein of insect muscle that in the sarcomeres binds to actin and alpha-actinin. To investigate kettin's functional role, we combined immunolabeling experiments with mechanical and biochemical studies on indirect flight muscle (IFM) myofibrils of Drosophila melanogaster. Micrographs of stretched IFM sarcomeres labeled with kettin antibodies revealed staining of the Z-disc periphery. After extraction of the kettin-associated actin, the A-band edges were also stained. In contrast, the staining pattern of projectin, another IFM-I-band protein, was not altered by actin removal. Force measurements were performed on single IFM myofibrils to establish the passive length-tension relationship and record passive stiffness. Stiffness decreased within seconds during gelsolin incubation and to a similar degree upon kettin digestion with mu-calpain. Immunoblotting demonstrated the presence of kettin isoforms in normal Drosophila IFM myofibrils and in myofibrils from an actin-null mutant. Dotblot analysis revealed binding of COOH-terminal kettin domains to myosin. We conclude that kettin is attached not only to actin but also to the end of the thick filament. Kettin along with projectin may constitute the elastic filament system of insect IFM and determine the muscle's high stiffness necessary for stretch activation. Possibly, the two proteins modulate myofibrillar stiffness by expressing different size isoforms.

Complex compounds of Pd(II), Pt(II), Cu(I) and Hg(II) with tertiary thioamides.

Synthesis and chemical and physical characterization of four new complex compounds of thiobenzpyrolidide [1-(pyrolidine)-thiobenzoyl] with Pd(II), Pt(II), Cu(I) and Hg(II) are presented. The purposed chemical structure for these complexes is suggested by the elemental chemical analysis, molecular mass measurements, electric conductivities as well as by UV-VIS and IR spectra. The obtained compounds may in principle be used as enzyme inhibitors having a pronounced insecticidal action.

Complex compounds of Pd(II), Pt(II), Ni(II), Hg(II) and Cu(I) with 1-benzylidene-2-phenazinoylhydrazine.

Synthesis and physical-chemistry characterization of five new genuine complex compounds of 1-Benzylidine-2-phenazinoylhydrazine with Pd(II), Pt(II), Ni(II), Hg(II) and Cu(I) are presented. The chemical structure for these complexes is suggested by the elemental chemical analysis, molecular mass measurements, electric conductivities as well as by IR and UV-VIS spectra. The metal:ligand molar ratio is found 1:1, the obtained complexes belonging to the square planar geometry D4h.