A nutraceutical formulation combined with sclerofoam-assisted laser treatment ameliorates chronic venous insufficiency.

Chronic venous insufficiency has a high impact on the healthcare system due to its high incidence worldwide. We performed a study in 30 women with thigh and leg varices due to major saphenous vein valve incontinence with saphenous trunk reflux causing phlebo-lymphoedema to assess the efficacy of sclerofoam-assisted laser treatment combined with nutraceutical administration. The patients underwent endovascular combination sealing of the saphenous trunk with sclerofoam-assisted laser treatment technique into the major saphenous veins under low-volume tumescent anesthesia followed by intraoperative phlebectomies. Post-operatively, the patients received capsules containing Aesculus Hippocastanum, chondroitin sulphate, proanthocyanidins from Pinus pinaster Aiton, proanthocyanidins from Vitis vinifera L., hydrolysed marine collagen and carcinine dihydrochloride for 3 weeks. We evaluated the extracellular fluid volume of the lower limbs using bioimpedance spectroscopy pre- (T0) and post-surgery (T2) (impedance is a vector which is composed of two components, resistance [RES] and reactance [REA)]). In addition, we evaluated the following parameters pre- and post-surgery: pain, heaviness, paresthesia, itching, swelling, daily urine volume output and leg volume. Limb volume was significantly decreased at T2 compared to T0 (p < 0.01). RES and REA were significantly increased at T2 compared to T0 (p < 0.0001 and p < 0.01, respectively). A significant improvement in heaviness, paresthesia, pain, swelling and itch was also observed (all p < 0.0001) while no changes in terms of diuresis occurred. No adverse effects were observed. The present study shows a promising approach to the treatment of chronic venous insufficiency that warrants further clinical studies in larger cohorts of patients.

Cosmetic penile enhancement surgery: a 3-year single-centre retrospective clinical evaluation of 355 cases.

Men's satisfaction and sexual function is influenced by discomfort over genital size which leads to seek surgical and non-surgical solutions for penis alteration. In this article we report the results of a retrospective study of 355 cases of cosmetic elongation, enlargement and combined elongation and enlargement phalloplasty. We found a significant improvement in length at rest, stretched length and circumference at rest at 2, 6 and 12 months post-surgical procedure (all p < 0.0001). 5-item International Index of Erectile Function (IIEF-5) was also increased at 12 months post-surgery compared to baseline (p < 0.0001). This was consistent with an IIEF-5 improvement of 6.74% compared to baseline. This study is clinically relevant due to the large cohort of patients included and because it is the first study to use an inverse periosteal-fascial suture not described previously as part of the surgical methodology.

Feasibility single-arm study of a medical device containing Desmodium adscendens and Lithothamnium calcareum combined with chemotherapy in head and neck cancer patients.

BACKGROUND: Neoplasms of the head and neck represent approximately 5% of cancers and they require complex multidisciplinary clinical management. Desmodium adscendens (Desmodium) is a plant that possesses anti-allergic, antioxidant and hepatoprotective properties. Lithothamnium calcareum (Lithothamnium) is a calcified seaweed that possesses remineralization properties and the ability to maintain homeostasis. AIM: In this single-arm study, we investigated the efficacy of a combination therapy based on Desmovit® which contains Desmodium and Lithothamnium, and chemotherapy in patients with head and neck cancer. METHODS: Twelve patients with histological or cytological diagnosis of stage IV head and neck cancer were enrolled in this study that was approved by the ethics committee of the Unità Operativa Complessa (UOC) di Oncologia Medica Azienda Ospedaliera Ospedali Riuniti Marche Nord and followed the Declaration of Helsinki guidelines. The patients were monitored by investigation of the performance status according to the Glasgow Prognostic Score (GPS), which evaluates the plasma level of C-reactive protein and albumin levels, and the Eastern Cooperative Oncology Group (ECOG) examination. Pain and fatigue were also monitored using the visual analog scale and visual analog fatigue scale, respectively. All the above parameters were assessed biweekly to week 10. RESULTS: GPS, ECOG, and albumin remained stable throughout the study with a trend towards a decrease in GPS and albumin at week 10 post-treatment. Pain significantly improved at week 8 (P<0.05) while fatigue improved at weeks 8 and 10 (all P<0.01). CONCLUSION: We found that chemotherapy, combined with Desmodium and Lithothamnium, improved pain and fatigue in head and neck cancer patients, although we cannot confirm if this was due to Desmodium and Lithothamnium or chemotherapy. The improvement in pain and fatigue was supported by the ECOG performance status remaining stable with the highest score being equal to 2 throughout the study and a trend towards an improvement in GPS performance status and albumin levels.

Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS.

Of familial amyotrophic lateral sclerosis (fALS) cases, 20% are caused by mutations in the gene encoding human cytosolic Cu/Zn superoxide dismutase (hSOD1). Efficient translation of the therapeutic potential of RNAi for the treatment of SOD1-ALS patients requires the development of vectors that are free of significant off-target effects and with reliable biomarkers to discern sufficient target engagement and correct dosing. Using adeno-associated virus serotype 9 to deliver RNAi against hSOD1 in the SOD1G93A mouse model, we found that intrathecal injection of the therapeutic vector via the cisterna magna delayed onset of disease, decreased motor neuron death at end stage by up to 88%, and prolonged the median survival of SOD1G93A mice by up to 42%. To our knowledge, this is the first report to demonstrate no significant off-target effects linked to hSOD1 silencing, providing further confidence in the specificity of this approach. We also report the measurement of cerebrospinal fluid (CSF) hSOD1 protein levels as a biomarker of effective dosing and efficacy of hSOD1 knockdown. Together, these data provide further confidence in the safety of the clinical therapeutic vector. The CSF biomarker will be a useful measure of biological activity for translation into human clinical trials.

A hyaluronic acid- and chondroitin sulfate-based medical device improves gastritis pain, discomfort, and endoscopic features.

Gastritis is an inflammation of the gastric mucosa. In this study, we investigated the efficacy of a medical device, Esoxx®, based on hyaluronic acid and chondroitin sulfate on gastritis-related upper abdominal pain/discomfort and endoscopic features. Fifty patients, affected by gastritis, were randomised to receive the medical device or placebo. The primary endpoint was the medical device efficacy on upper abdominal pain/discomfort associated with gastritis and measured by Visual Analogue Scale (VAS). The secondary endpoints were the efficacy of the medical device on gastritis-related mucosal erosions, blood oozing, and hyperemia (redness)/edema, as assessed by endoscopy, and the patients' rating of their compliance with the treatments. A significant reduction in VAS pain was observed in the treatment group after a 5-week treatment, if compared with placebo (p < 0.001). In summary, administration of a medical device, based on hyaluronic acid and chondroitin sulfate, improves gastritis-related upper abdominal pain/discomfort and decreases mucosal erosions, blood oozing, and hyperemia (redness)/edema at 5-week follow-up in patients affected by gastritis.

A Novel Role for Lymphotactin (XCL1) Signaling in the Nervous System: XCL1 Acts via its Receptor XCR1 to Increase Trigeminal Neuronal Excitability.

Chemokines are known to have a role in the nervous system, influencing a range of processes including the development of chronic pain. To date there are very few studies describing the functions of the chemokine lymphotactin (XCL1) or its receptor (XCR1) in the nervous system. We investigated the role of the XCL1-XCR1 axis in nociceptive processing, using a combination of immunohistochemical, pharmacological and electrophysiological techniques. Expression of XCR1 in the rat mental nerve was elevated 3 days following chronic constriction injury (CCI), compared with 11 days post-CCI and sham controls. XCR1 co-existed with neuronal marker PGP9.5, leukocyte common antigen CD45 and Schwann cell marker S-100. In the trigeminal root and white matter of the brainstem, XCR1-positive cells co-expressed the oligodendrocyte marker Olig2. In trigeminal subnucleus caudalis (Vc), XCR1 immunoreactivity was present in the outer laminae and was colocalized with vesicular glutamate transporter 2 (VGlut2), but not calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4). Incubation of brainstem slices with XCL1 induced activation of c-Fos, ERK and p38 in the superficial layers of Vc, and enhanced levels of intrinsic excitability. These effects were blocked by the XCR1 antagonist viral CC chemokine macrophage inhibitory protein-II (vMIP-II). This study has identified for the first time a role for XCL1-XCR1 in nociceptive processing, demonstrating upregulation of XCR1 at nerve injury sites and identifying XCL1 as a modulator of central excitability and signaling via XCR1 in Vc, a key area for modulation of orofacial pain, thus indicating XCR1 as a potential target for novel analgesics.

Mouse Platelet Ral GTPases Control P-Selectin Surface Expression, Regulating Platelet-Leukocyte Interaction.

OBJECTIVE: RalA and RalB GTPases are important regulators of cell growth, cancer metastasis, and granule secretion. The purpose of this study was to determine the role of Ral GTPases in platelets with the use of platelet-specific gene-knockout mouse models. APPROACH AND RESULTS: This study shows that platelets from double knockout mice, in which both GTPases have been deleted, show markedly diminished (≈85% reduction) P-selectin translocation to the surface membrane, suggesting a critical role in α-granule secretion. Surprisingly, however, there were only minor effects on stimulated release of soluble α- and δ-granule content, with no alteration in granule count, morphology, or content. In addition, their expression was not essential for platelet aggregation or thrombus formation. However, absence of surface P-selectin caused a marked reduction (≈70%) in platelet-leukocyte interactions in blood from RalAB double knockout mice, suggesting a role for platelet Rals in platelet-mediated inflammation. CONCLUSIONS: Platelet Ral GTPases primarily control P-selectin surface expression, in turn regulating platelet-leukocyte interaction. Ral GTPases could therefore be important novel targets for the selective control of platelet-mediated immune cell recruitment and inflammatory disease.

Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.

Schizophrenia is a debilitating disorder that may have a neurodevelopmental origin. For this reason, animal models based on neonatal insults or manipulations have been extensively used to demonstrate schizophrenia-related behaviors. Among those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model of schizophrenia-related behavior as it mimics behavioral and neurochemical abnormalities often seen in schizophrenic patients including hyperlocomotion in a novel environment. To investigate the neuroanatomical basis of coding novelty in the nVHL rat, we assessed the behavioral locomotor activity paradigm in a novel environment and measured expression of c-Fos, a marker of neural activation, in brain regions involved in the process of coding novelty or locomotion. Upon reaching adulthood, nVHL rats showed hyperlocomotion in the novel environment paradigm. Moreover, in nVHL rats the expression of c-Fos was greater in the prefrontal cortex (PFC) and CA1 region of the dorsal hippocampus compared to sham rats. Whereas similar expression of c-Fos was observed in the basolateral amygdala, nucleus accumbens and dentate gyrus region of  hippocampus of nVHL and sham rats. These results suggest that the nVHL disrupts the neural activity in the PFC and CA1 region of hippocampus in the process of coding novelty in the rat.

Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits.

Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two major pathologies stemming from the hexanucleotide RNA expansions (HREs) have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN) dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV) and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ) abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43) pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

Endoplasmic reticulum-mitochondria Ca2+ crosstalk in the control of the tumor cell fate.

Mitochondria-associated membranes are juxtaposed between the endoplasmic reticulum and mitochondria and have been identified as a critical hub in the regulation of apoptosis and tumor growth. One key function of mitochondria-associated membranes is to provide asylum to a number of proteins with tumor suppressor and oncogenic properties. In this review, we discuss how Ca2+ flux manipulation represents the primary mechanism underlying the action of several oncogenes and tumor-suppressor genes and how these networks might be manipulated to provide novel therapies for cancer. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology.

Cancer is one of the most common causes of death worldwide. Available treatments are associated with numerous side effects and only a low percentage of patients achieve complete remission. Therefore, there is a strong need for new therapeutic strategies. In this regard, pulsed electromagnetic field (PEMF) therapy presents several potential advantages including non-invasiveness, safety, lack of toxicity for non-cancerous cells, and the possibility of being combined with other available therapies. Indeed, PEMF stimulation has already been used in the context of various cancer types including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo. At present, only limited application of PEMF in cancer has been documented in humans. In this article, we review the experimental and clinical evidence of PEMF therapy discussing future perspectives in its use in oncology.

Intersection of mitochondrial fission and fusion machinery with apoptotic pathways: Role of Mcl-1.

Mitochondria actively contribute to apoptotic cell death through mechanisms including the loss of integrity of the outer mitochondrial membrane, the release of intermembrane space proteins, such as cytochrome c, in the cytosol and the caspase cascade activation. This process is the result of careful cooperation not only among members of the Bcl-2 family but also dynamin-related proteins. These events are often accompanied by fission of the organelle, thus linking mitochondrial dynamics to apoptosis. Emerging evidences are suggesting a fine regulation of mitochondrial morphology by Bcl-2 family members and active participation of fission-fusion proteins in apoptosis. The debate whether in mitochondrial morphogenesis the role of Bcl-2 family members is functionally distinct from their role in apoptosis is still open and, above all, which morphological changes are associated with cell death sensitisation. This review will cover the findings on how the mitochondrial fission and fusion machinery may intersect apoptotic pathways focusing on recent advances on the key role played by Mcl-1.

Mechanisms and therapeutic effectiveness of lactobacilli.

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword 'Lactobacillus'. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects.

Effectiveness and Safety of Arnica montana in Post-Surgical Setting, Pain and Inflammation.

Arnica montana has been widely used as a homeopathic remedy for the treatment of several inflammatory conditions in pain management and postoperative settings. This review gives an overview of the therapeutic use of Arnica montana in the above-mentioned fields also focusing on its mechanisms of action learned from animal models and in vitro studies. Arnica montana is more effective than placebo when used for the treatment of several conditions including post-traumatic and postoperative pain, edema, and ecchymosis. However, its dosages and preparations used have produced substantial differences in the clinical outcome. Cumulative evidence suggests that Arnica montana may represent a valid alternative to non-steroidal anti-inflammatory drugs, at least when treating some specific conditions.

Onco-epidemiology of domestic animals and targeted therapeutic attempts: perspectives on human oncology.

The spontaneous tumor biology has been investigated with the support of animalists using animals as a preclinical model allowing translation of results in clinical practice. This review provides an insight into the field of comparative oncology. Evidence shows that companion animal health care is impressively growing in terms of development of new therapies and diagnostic tools, nutrition and disease prevention. However, even if most animal tumors might be a reliable model to study human carcinomas, many open questions, related to the opportunities to select and recruit new models in oncology, along with their legal and ethical implications, remain unanswered.

Palmieri's double suture skin repair: a new double suture approach to cases of skin cancer and ulcerative lesions.

We describe two case reports to assess the efficacy of a new method suitable to close small-sized pressure ulcers and cancer-related skin lesions.

A new highly viscoelastic hyaluronic acid gel: rheological properties, biocompatibility and clinical investigation in esthetic and restorative surgery.

Nowadays there is an increased demand for safe and effective volume enhancing fillers to achieve soft tissue augmentation in order to overcome tissue defects and aging-associated skin changes. In the present study we characterized the rheological and biological properties of Variofill(®), a new highly viscoelastic hyaluronic acid gel, by investigating the local effects following subcutaneous implantation in the rat to detect the host-tissue reactions and biodegradation over 18 months. We also investigated, for the first time, the application of Variofill(®) in esthetic and restorative surgery in two medical case reports. In the first case report we successfully performed Variofill(®) treatment to improve facial scars in a patient previously involved in a car crash. In the second case report we carried out a novel procedure involving a high-dose (1000 ml) injection of Variofill(®) into the dermis and subcutis of the abdominal quadrants in order to allow a classic reconstructive procedure of the abdominal wall in a patient presenting a wide incisional hernia.

The feasibility of a fiber optic laser approach to relieving lymphedematous syndrome: a case report.

Here we report a case of successful fiber optic laser treatment of lymphedema in a swollen arm post mastectomy. At the moment, this procedure has only anecdotal evidence to justify its use, but in our experience is a feasible, minimally invasive day-stay procedure which has been demonstrated to be safe and effective. Further nonhomogeneous case pooling and follow-up would enable guidelines and definite surgical protocols for its use to be implemented.

A preliminary study to assess the efficacy of a new UVA1 laser for treatment of psoriasis.

OBJECTIVE: The aim of the present study was to assess the effectiveness of an UVA1 355 nm laser (Alba 355) for treatment of mild, moderate, and severe psoriasis. BACKGROUND DATA: Psoriasis is an immune-inflammatory and proliferative skin disease. During the past few years, the instrumental treatment by UV radiation has been successfully described, either alone or in combination with topical and/or systemic drug administration to treat several skin-related diseases. MATERIALS AND METHODS: Fourteen patients, aged between 25 and 50 years (37.7±2.3 [mean±SEM]), affected by mild-to-severe psoriatic plaques, were included in this study. Patients were treated with a new instrument, laser Alba 355, which administers energy in the UVA1 spectrum. This instrument is based on a 1064 wavelength neodymium-doped yttrium orthovanadate (Nd:YVO4) laser optically pumped using a 808 nm infrared beam able to achieve a third harmonic 355 nm wave delivery. The fluences administered were 80-140 J/cm2 four times a week for a total of up to 12 sessions over selected psoriatic plaques in different areas of the patients' bodies. The patients rated their satisfaction with the outcome of the procedure as 1 not satisfied, 2 quite satisfied, 3 very satisfied. RESULTS: Overall, laser treatment of psoriatic plaques produced a significant improvement in Psoriasis Area and Severity Index (PASI) score (F [3, 55]=57.86; p<0.001). The mean PASI score decreased from a baseline value of 24.5±2.9 to a value of 15.6±1.9 at 1 week (p<0.001), 9.1±1.2 at 2 weeks (p<0.001), and 5.8±1.2 at 3 weeks (p<0.001). All the patients were very satisfied with the outcome of procedure. No side effects were observed in this study. CONCLUSIONS: The present study outlines an original approach based on UVA1 355 nm laser therapy for treatment of mild, moderate, and severe psoriasis. In the present study, the high success rate was coupled with safety. Larger clinical trials are needed to definitely support the role of this medical device not only for treatment of psoriasis, but also for other skin-related diseases that share a similar pathophysiology. We speculate that in the near future, the use of this laser will grow in the dermatology clinic.

Management of haemostasis in surgery: sealant and glue applications.

Blood loss has always been a sensitive issue in surgery. Traditional techniques, such as suturing and electrocautery, have drastically reduced operatory bleeding. Unfortunately, wound edges and point application devices are frequently characterized by bleeding and infections. Over the past 20 years, haemostatic agents and tissue sealants have been developed and now are currently used, along with classic suture in various surgical specialties. Their fluid nature allows management of blood loss along any point of the wound and tissue repair. This review presents an overview of the most diffused haemostatic sealants, focusing on their main use in surgery and their adverse effects.