Bovine Serum Amine Oxidase and Polyamine Analogues: Chemical Synthesis and Biological Evaluation Integrated with Molecular Docking and 3-D QSAR Studies.

Natural polyamines (PAs) are key players in cellular homeostasis by regulating cell growth and proliferation. Several observations highlight that PAs are also implicated in pathways regulating cell death. Indeed, the PA accumulation cytotoxic effect, maximized with the use of bovine serum amine oxidase (BSAO) enzyme, represents a valuable strategy against tumor progression. In the present study, along with the design, synthesis, and biological evaluation of a series of new spermine (Spm) analogues (1-23), a mixed structure-based (SB) and ligand-based (LB) protocol was applied. Binding modes of BSAO-PA modeled complexes led to clarify electrostatic and steric features likely affecting the BSAO-PA biochemical kinetics. LB and SB three-dimensional quantitative structure-activity relationship (Py-CoMFA and Py-ComBinE) models were developed by means of the 3d-qsar.com portal, and their analysis represents a strong basis for future design and synthesis of PA BSAO substrates for potential application in oxidative stress-induced chemotherapy.

Randomized Double-Blind Controlled Study on the Safety and Efficacy of a Novel Injectable Cross-linked Hyaluronic Gel for the Correction of Moderate-to-Severe Nasolabial Wrinkles.

INTRODUCTION: The current study compares two hyaluronic acid fillers, Ial System Duo and Belotero Basic/Balance, for the treatment of wrinkles. MATERIALS AND METHODS: This is a single-center, double-blind randomized controlled study. Inclusion criteria consisted of subjects with bilateral nasolabial wrinkles. Each subject was treated with both products: One was applied on the right side and the other on the left side of the face. The quantity of product injected and any problems or local reactions (erythema, edema, pain or itching) were recorded and reassessed at 3 and 6 months and then monthly until complete absorption of the product. The Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS) were used for the assessment, as well as an ultrasound measurement of the skin thickness. RESULTS: Complete data were available for 59 subjects. At 3 and 6 months, both products showed improvement in the WSRS and GAIS score in the areas treated compared to pre-treatment assessments, although no significant differences were observed between them. No resulting significant differences were observed on skin thickness among the two products, which were completely reabsorbed in 285 ± 34 days (Ial System Duo) and 277 ± 34 days (Belotero Basic/Balance; Student's t test: p = 0.2181). No significant differences were observed with regard to the subject's satisfaction and adverse events. CONCLUSIONS: The Ial System Duo achieves long-term permanence (more than 9 months confirmed by ultrasound) in correction of moderate and severe wrinkles, similar to Belotero Basic/Balance. Both products showed a high safety profile and a high degree of subject and physician satisfaction. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Non-surgical treatment of deep wounds triggered by harmful physical and chemical agents: a successful combined use of collagenase and hyaluronic acid.

Some chronic ulcers often occur with slough, not progressing through the normal stages of wound healing. Treatment is long and other therapies need to be performed in addition to surgery. Patients not eligible for surgery because of ASA class (American Society of Anesthesiologists class) appear to benefit from chemical therapy with collagenase or hydrocolloids in order to prepare the wound bed, promoting the healing process. We describe four cases of traumatic, upper limb deep wounds caused by different physical and chemical agents, emphasising the effectiveness of treatment based on topical application of collagenase and hyaluronic acid (HA) before standardised surgical procedures. We performed careful disinfection of lesions combined with application of topical cream containing hyaluronic acid, bacterial fermented sodium hyaluronate (0·2%w/w) salt, and bacterial collagenase obtained from non-pathogenic Vibrio alginolyticus (>2·0 nkat1/g). In one patient a dermo-epidermal graft was used to cover the wide loss of substance. In two patients application of a HA-based dermal substitute was done. We obtained successful results in terms of wound healing, with satisfactory aesthetic result and optimal recovery of the affected limb functionality. Topical application of collagenase and HA, alone or before standardised surgical procedures allows faster wound healing.

Diabetic foot infection treatment and care.

Foot infections in diabetic patients are a common, complex and costly problem. They are potentially adverse with progression to deeper spaces and tissues and are associated with severe complications. The management of diabetic foot infection (DFI) requires a prompt and systematic approach to achieve more successful outcomes and to ultimately avoid amputations. This study reviews a multi-step treatment for DFIs. Between September 2010 and September 2012, a total of about 37 patients were consulted for DFI. The treatment algorithm included four steps, that is, several types of debridement according to the type of wound, the application of negative pressure therapy (NPT), other advanced dressings, a targeted antibiotic therapy local or systemic as the case may, and, if necessary, reconstructive surgery. This treatment protocol showed excellent outcomes, allowing us to avoid amputation in most difficult cases. Only about 8% of patients require amputation. This treatment protocol and a multidisciplinary approach with a specialised team produced excellent results in the treatment of DFI and in the management of diabetic foot in general, allowing us to improve the quality of life of diabetic patients and also to ensure cost savings.

Effect of enzymatic debridement with two different collagenases versus mechanical debridement on chronic hard-to-heal wounds.

A chronic ulcer is usually defined as an injury that does not spontaneously evolve towards healing and does not progress through normal healing stages such as inflammation, proliferation and remodelling. This study was designed in order to compare two types of collagenases with mechanical debridement alone. It was thus possible to evaluate their differences in terms of pain and debridement efficacy. Patients were divided into three groups: 30 patients were daily dressed using an ointment based on collagenase produced by Vibrio alginolyticus (B group), 30 patients were daily dressed using an ointment based on a collagenase preparation derived from Clostridium histolyticum (N group) and 30 patients underwent classical mechanical debridement (M group). Complete wound healing over a period of 8 weeks occurred in 24 patients (27%) out of 90;10 patients belonging to the B group, 8 patients to the N group and 6 patients to the M group. This study was performed in order to highlight the differences between two commercially available collagenase-based ointments in comparison with mechanical debridement alone. At the final time point of week, the difference in the percentage of debridement was not statistically significant in all groups, but at 4 weeks, the debrided area in the B group was larger with respect to the N and M groups, suggesting a more rapid wound bed cleansing process. On the basis of our experience, collagenase derived from V. alginolyticus with hyaluronic acid showed chemical and physical properties that make it a product of great manageability and ensure the protection of peri-wound skin. Moreover, less pain was experienced by the patients.

Reconstruction after skin cancer excision through a dermal induction template: our experience.

Dermal substitutes offer alternative approaches for wounds of all thicknesses where sufficient donation sites are not available for self-grafts. Several dermal substitutes are described in literature. This study included 20 patients treated with a dermal induction template after the removal of malignant skin cancers situated in various parts of the body. The participants were especially aged patients with multiple skin cancers, and complex clinical conditions, often affected by pathologies such as cardiopathy, diabetes mellitus, and hypercholesterolaemia, and receiving pharmacological multi-therapies, particularly antiplatelets and anticoagulants. In many of these patients, the general complex clinical picture provided significant contraindication for complex reconstructive surgery because of the high risk involved. All patients achieved complete healing about 8 weeks after the first surgery. By using a dermal induction template, it was possible to cover substantial loss of substances without the need of autologous tissue, with smoother and less apparent scar, minor occurrence of hypertrophic and retracted scars, better flexibility of healed skin and therefore a better result from an aesthetic point of view.

Evaluation of a new hyaluronic acid dermal filler for volume restoration.

OBJECTIVES: The present study aimed to evaluate the effectiveness and safety of hyaluronic acid gel for the treatment of volume loss or contour deficiency. METHODS: This 6-month, open-label study recruited sixty adults aged 40-65 years with bilateral moderate to severe volume loss or contour deficiency (Facial Volume Loss Scale [FVLS] score: 2-5). Eligible subjects were treated at the baseline visit with an injection of hyaluronic acid gel in one or more of three facial subregions: the zygomatic malar region, the anteromedial cheek and nasolabial folds. RESULTS: A significant improvement from baseline was observed in the FVLS score at each study visit up to 6 months post treatment (p < 0.0125 by Wilcoxon test). A significant improvement was also observed in the Global Aesthetic Improvement Scale (GAIS) at each visit up to 6 months. The study showed that the GAIS score improved in 100% of subjects at month 3, while at the end of the study (month 6) the percentage of improved subjects decreased to 91. Treatment effect was maintained by 100% of subjects up to month 3, while 57% of subjects showed a persistence of effect up to month 6. CONCLUSIONS: Volume loss or contour deficiency may be safely and effectively corrected using the new dermal filler.

Ten years of experience in chronic ulcers and malignant transformation.

Malignant degeneration of wounds is rare and often misdiagnosed. Delay in diagnosis may result in a worse prognosis. The aim of this study is to determine the number of skin cancers associated with chronic skin ulcers in our facility over a period of 10 years. Between January 2002 and December 2012, a total of about 1000 patients had consulted with us for chronic wounds, especially of vascular, diabetic and traumatic origin and pressure ulcers. Thirteen skin cancers had been detected: seven squamous cell and five basal cell carcinomas and one melanoma. We highlight how important it is to be aware of the signs suggesting a malignant change and the importance of biopsy at regular intervals during the life cycle of any chronic wound.

Intense pulsed light in the treatment of telangiectasias: case report of Behçet's disease with superficial vascular involvement.

Behçet's disease (BD) is a chronic systemic inflammatory disorder of unknown etiology with variable clinical manifestations. HLA-B51 allele is the most strongly associated known genetic factor. The mucocutaneous lesions (oral aphthae, genital aphthae, skin lesions such as pseudofolliculitis) constitute the hallmark of the disease, but also gastrointestinal, vascular, central nervous systems, and others may be involved. We report a case of a young man affected with Behçet's disease who presented facial telangiectasias and striae rubra in the inner region of his arms and at the level of his hips, as uncommon minor superficial vascular manifestations of BD. To manage them we have subjected the patient to a cycle of Intense Pulsed Light (IPL) therapy. Our findings showed that the use of IPL is a safe and effective treatment for telangiectasias and striae rubra, also in the complex clinical condition of Behçet's disease. In fact, the treatments were well tolerated, no sign of scarring or hyper/hypopigmentation was reported and we obtained a significant improvement of the lesions in terms of color and size of them.

Skin ulcer caused by venous extravasation of heroin.

The accidental leakage of the compound, in this case heroin, from the veins where it is injected, causes the formation of tissue lesions. Similar mechanisms lead to progressive tissue necrosis, which, if not immediately treated, results in the loss of the relevant function. A 57-year-old man presented a skin lesion on the posterior region of the left forearm with extensive necrosis of skin and subcutaneous layer involving the underlying muscle planes, caused by a venous extravasation of heroin that he reports having injected himself. The wound size is 15 × 10 cm; it had a sanious, fibrinous, secreting and smelly bottom. In this period, the patient was subjected to daily focused dressing before debridement of the lesion through a collagenase plus hyaluronic acid ointment: Bionect Start®; (FIDIA Pharmaceutical, Abano, Italy). The therapeutic choice was rewarded with a complete resolution of the wound through a non-invasive technique and over a short period. Avoiding the hospitalisation of the patient achieved a reduction of risks for him and of the costs for the National Health Service (NHS). The Bionect Start®; (FIDIA Pharmaceutical) as well as allowing the healing of the wound also decreased significantly the pain felt by the patient, the amount of exudate and the bad smell improving in a non-negligible way his quality of life.

'BLUES' procedure for assessing the blue level of the sclera in Osteogenesis Imperfecta.

PURPOSE: Blue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI. To address this medical need, this study is aimed to design and validate a new method called 'BLUES' (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI. METHODS: Sixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed. In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the 'BLUES' procedure to the judgement of experienced ophthalmologists (JEO). A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of 'BLUES' and 'JEO' were estimated versus the standard OI diagnosis. The K indexes of 'BLUES' versus 'JEO' were also evaluated. RESULTS: The optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835-0.945) and specificity of 87% (CI95%: 0.791-0.949) for the 'BLUES' procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of 'JEO' ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between 'BLUES 'and 'JEO' evaluations ranged from 0.613 to 0.734. CONCLUSIONS: Our findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The 'BLUES' procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI.

Does choroidal thickness predict persistent subretinal fluid after rhegmatogenous retinal detachment repair? A retrospective study with fellow eye comparison.

PURPOSE: To evaluate whether choroidal thickness (CT) is associated with persistent subretinal fluid (pSRF) after simple primary rhegmatogenous retinal detachment (RRD) repair. METHODS: This single-centre, retrospective, observational study included patients who underwent RRD repair with at least 12-month follow-up. Preoperative and postoperative parameters were evaluated for association with pSRF. CT measurements were obtained at the central 1 mm area on enhanced depth imaging (EDI) OCT scans, using a semiautomatic method. Multiple logistic regression analyses were assessed to determine predictive factors for pSRF. RESULTS: Overall, 100 eyes of 100 patients, mean age of 59.9 ± 12.6 years were included. pSRF was found in 21.0% of eyes and resolved over time in 85.7% of eyes at 12 months. In the pSRF group both RRD and fellow eyes showed lower mean choroidal and RPE thickness values as compared to those without pSRF (p < 0.05). A significant correlation was found between pSRF occurrence and choroidal thinning (p = 0.02). After multiple regression analyses, macula-off RRD (p = 0.005) and scleral buckling (SB) technique (p = 0.001) were retained as final predictors for pSRF. In macula-off SB eyes, detachment duration was the only factor associated with pSRF (p = 0.046). There were no significant differences in best-corrected visual acuity outcomes between the pSRF and the no-pSRF eyes. CONCLUSIONS: Patients with pSRF showed lower choroidal and RPE thickness as compared to those without pSRF. CT did not turn out to be a final predictor for pSRF, as this was mainly associated with macular involvement, surgical technique and detachment duration.

Extracorporeal shock wave therapy for the management of burn scars.

BACKGROUND: Hypertrophic and contracture scars are common problems after burn injuries and cause functional and cosmetic deformities. A wide variety of treatments has been advocated for postburn pathologic scars regression. Unfortunately, the reported efficacy has been variable. OBJECTIVES: To investigate the use of extracorporeal shock wave therapy (ESWT), which mainly targets the fibroblasts in scar tissue, as an effective modality for scar treatment in burn patients. MATERIALS AND METHODS: An experimental study with ESWT was performed in 16 patients with postburn scars contractures, hypertrophic scars, or keloids twice a week for 6 weeks. Digital photographs were obtained and visual analogue scales were completed before and after treatment. RESULTS: Already after the first session, scars appeared more pliable, and color mismatch was less evident. At the end of the study period, all treated scars obtained a more acceptable appearance. CONCLUSIONS: Extracorporeal shock wave therapy is a feasible and cost-effective treatment in the management of postburn pathologic scars.

Island pedicle and bilobed flaps in ala and back nose reconstruction: a prospective comparative analysis.

BACKGROUND: Reconstruction of face deformities resulting from skin cancer includes reconstructing the area with similar tissue. This prospective study aimed to compare the functional and aesthetic outcomes between two types of local flaps (the island pedicle flap vs the bilobed flap) used in reconstruction of the ala and back nose. METHODS: In this study, 120 patients with skin cancer of the nose underwent ala and back reconstruction: 60 patients using the island flap (IF group) and 60 patients using the bilobed flap (BF group). The two groups were homogeneous for sex, age, and anatomic area. Complications, scarring according to the scale of Vancouver, cosmetic appearance, and disorders of sensations were analyzed, and statistical analysis was performed using Chi-square and analysis of variance (ANOVA). RESULTS: Early complications were more common in the BF group than in the IF group (p < 0.005). The Vancouver Scar Scale scores were significantly better for the IF patients (p < 0,005), who also showed better results in the analysis of cosmetic outcomes (p < 0.005). CONCLUSION: The study showed that the island flap used for ala and back nose reconstruction provides better functional and cosmetic results than the bilobed flap, from both functional and aesthetic points of view. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article.

Use of the Z-plasty technique in nasal skin cancers. Two clinical cases.

Basal cell carcinoma (BCC) is the most common type of cancer in Europe, Australia and the U.S.A. After nasal skin cancer excision, especially if it is less than 1-2 cm in diameter, several surgical techniques can be used to reconstruct the lack of substance.In the management of our two patients we have chosen to utilize, instead, a well-known plastic surgery technique, Z-plasty, which is both easy to perform that effective to achieve excellent cosmetic results. As shown by our two clinical cases, the use of Z-plasty for lack of substance of the nose tip and bridge can be extremely effective in terms of cosmetic results. In comparison with the other reconstructive techniques, in fact, it is very easy to perform and allows to avoid or minimize the distortion of the nasal tip and wing, to orient the incision along the skin tension lines and, finally, to replace the lack with very similar structures regarding color, thickness and tissue architecture to those removed.

Extracorporeal shock wave therapy for the treatment of venous ulcers in the lower limbs.

Chronic venous ulcers are one of the most common medical problems today. The treatment has always been challenging and over the years many conservative and surgical alternatives have been proposed. During the past three decades, extracorporeal shock wave therapy (ESWT) has been introduced in several medical specialties. According to the clinical findings, the ESWT appears to significantly improve the healing process of chronic wounds, increasing the release of endogenous angiogenic factor from endothelial cells and fibroblasts, consequently fastening the healing process of chronic wounds. The present report describes the application of ESWT for the treatment of chronic venous ulcers in the lower limbs and compared the results with those obtained by conventional treatment on the contralateral leg.

[Neuromodulation in the treatment of hand's scars]. / Neuromodulazione nel trattamento delle cicatrici della mano.

AIM: In the present study, we investigated effects of a local anesthetic, in the treatment of pathologic scars. MATERIALS AND METHODS: this retrospective report describes our experience with 97 patients who underwent lidocaine 2% injections in surgical scars of the hand. The results were evaluated using 4 parameters: cutaneous structure, pain, thikness and colour of the scar. RESULTS: The mean outcome was the pain control. 2 out of 97 showed a 100% improvement in all the parameters. In 95 of 97 patients the improvement was between 60-100%. DISCUSSION: Lidocaine controls different pathways of inflammation. Flogosis is the first phase of cicatrization and so lidocaine could be used in the treatment of pathologic scars. A previous study confirms the role of lidocaine, injected to control the pillar pain in the carpal tunnel's surgery in the improvement of scars. CONCLUSION: Lidocaine, as neuromodulation treatment, acts on inflammation, temperature, perfusion and partial pressure of oxygen.

Surgical correction of gynecomastia in thin patients.

BACKGROUND: Gynecomastia refers to a benign enlargement of the male breast. This article describes the authors' method of using power-assisted liposuction and gland removal through a subareolar incision for thin patients. METHODS: Power-assisted liposuction is performed for removal of fatty breast tissue in the chest area to allow skin retraction. The subareolar incision is used to remove glandular tissue from a male subject considered to be within a normal weight range but who has bilateral grade 1 or 2 gynecomastia. RESULTS: Gynecomastia correction was successfully performed for all the patients. The average volume of aspirated fat breast was 100-200 ml on each side. Each breast had 5-80 g of breast tissue removed. At the 3-month, 6-month, and 1-year follow-up assessments, all the treated patients were satisfied with their aesthetic results. CONCLUSIONS: Liposuction has the advantages of reducing the fat tissue where necessary to allow skin retraction and of reducing the traces left by surgery. The combination of surgical excision and power-assisted lipoplasty also is a valid choice for the treatment of thin patients.

[Macromastia surgical therapy]. / La terapia chirurgica della gigantomastia.

AIM: Macromastia is a social health problem that causes high discomfort in the patients. Goals of reduction mammaplasty are to alleviate physical emotional and psychosocial problems and to restore a conical shaped breast, maintaining scars as short as possible. We report our approach for reduction mammaplasty with superior pedicle. MATERIALS OF STUDY: Our method combines advantages of round block with vertical scar, using a dermal flap that is fixed to the new mammary crease. We analyzed skin and glandular resection customizing the mammaplasty. RESULTS: The dermal flap works against the weight of residual tissue, maintaining the crease at the desired position with natural result. Benefits are an excellent projection, short scar, suitable reshaping and patient satisfaction. DISCUSSION AND CONCLUSIONS: This technique can be used for mild to severe hypertrophy with various degrees of ptosis. It results in a successful aesthetic outcome with minimal scarring suitable breast remodelling and natural long-lasting projection.

[Metatypical basal-cell carcinoma (MTC) or basosquamos carcinoma (BSC): surgical therapy]. / Carcinoma a cellule basali metatipiche (MTC) o carcinoma basosquamoso (BSC): terapia chirurgica.

AIM: Nonmelanoma skin cancer (NMSC) is the most common cancer in the world with an incidence 18-20 times greater than that of malignant melanoma. Basal cell carcinoma, which probably arises from immature pluripotential cells, is the most common malignant tumor of the skin in Caucasian. It occurs mostly on sun-exposed areas such as neck and face. MATERIAL OR STUDY: We performed a retrospective study of 327 consecutive patients, diagnosed for metatypical basal cell carcinoma. Tumors were analyzed and measured from the surgeon, excision margins were marked on the basis of palpable or visual alteration of the burden. The minimum surgical margin was equal to the short axis of the ellipse. Therapy was made according to guidelines. RESULTS: A relevant difference came out between two genders. 213 Males (65%) were affected in comparison with only 114 females (35%). Concerning areas affected, first is cervico-facial area with a prevalence of 220 cases (67.3%), second trunk 33 cases (10.1%), third other areas 29 cases (8.86%), fourth limbs 32 cases (9.80%), fifth scalp with 13 cases (4%). DISCUSSION AND CONCLUSIONS: Diagnosis is based on histological analysis. Histologically MTC is divided into two subtypes: intermediated and mixed. In the intermediate form transitional zones and tumor islets are found together, thus combining features of BCC and SCC In mixed subtype typical basal cells coexist with areas of conglomerated squamous cells, squamous pearls could be present.