Clinical and experimental applications of sodium phenylbutyrate

Histone acetyltransferase and histone deacetylase are enzymes responsible for histone acetylation and deacetylation, respectively, in which the histones are acetylated and deacetylated on lysine residues in the N-terminal tail and on the surface of the nucleosome core. These processes are considered the most important epigenetic mechanisms for remodeling the chromatin structure and controlling the gene expression. Histone acetylation is associated with gene activation. Sodium phenylbutyrate is a histone deacetylase inhibitor that has been approved for treatement of urea cycle disorders and is under investigation in cancer, hemoglobinopathies, motor neuron diseases, and cystic fibrosis clinical trials. Due to its characteristics, not only of histone deacetylase inhibitor, but also of ammonia sink and chemical chaperone, the interest towards this molecule is growing worldwide. This review aims to update the current literature, involving the use of sodium phenylbutyrate in experimental studies and clinical trials

Clinical effects of overwintered-stressed Chondrus Crispus and non-overwintered-stressed Chondrus crispus dietary supplementations

Background: Chondrus crispus is red seaweed widespread in the northern Atlantic coasts due to the high proteins, burden it is quite helpful supplement for some symptoms such as fatigue, asthenia, and weakness and for supporting skeletal muscles in sports athletes.Aims and Objectives: This retrospective observational "not inferiority" study investigates and compares the clinical effects of overwintered-stressed Chondrus Crispus and non-overwintered-stressed Chondrus crispus dietary supplementations for the treatment of musculoskeletal and articular symptomatology related diseases.Materials and Methods: Eighty patients were retrospectively reviewed through the Second Opinion Medical Network. Patients were prescribed 3 capsules/day after the main meals for 3 weeks of overwintered-stressed Chondrus Crispus or non-overwintered stressed Chondrus crispus dietary supplementations. Quality of life (QOL) assessment was evaluated by the Short Form-36 (SF-36) health survey questionnaire before starting the treatment and after the third week. Benefits declared by patients were also reported after the treatment in addition to some subjective observations related to the symptomatology and to the health status.Results: Fifty patients were treated with overwintered-stressed Chondrus Crispus and 30 patients were treated with the non-overwintered-stressed Chondrus crispus dietary supplementation. The general benefit of treatment with overwintered-stressed Chondrus Crispus was 76%, while that obtained with non-overwintered-stressed Chondrus crispus was 33.3% (P <0.01). Results of SF-36 general health status after the treatment demonstrated that 37 patients (74%) and 11 patients (36.7%) felt better than before in the overwintered-stressed Chondrus Crispus group and non-overwintered-stressed Chondrus crispus group, respectively (P < 0.01). A great improvement of subjective exhaustion, fatigue, pain, digestive, and peristalsis disturbances symptoms, in addition to mood and concentration amelioration that would be a consequence of symptomatology regression, was also observed.Conclusions: This retrospective observational comparative study evidences that overwintered-stressed Chondrus Crispus improved musculoskeletal and articular symptomatology related diseases better than non-overwintered-stressed Chondrus crispus.Asian Journal of Medical Sciences Vol.9(6) 2018 7-1

A pilot study to compare two different hyaluronic acid compounds for treatment of knee osteoarthritis.

Osteoarthritis is characterized by progressive articular cartilage degeneration, changes in subchondral bone and synovial inflammation, leading to pain and disability. Viscosupplementation with hyaluronic acid has been widely investigated due to the viscoelastic properties of this compound to manage pain improving the ability to perform daily activities in patients affected by osteoarthritis. In the present study we investigated the clinical effectiveness of viscosupplementation with a new highly cross-linked hyaluronic acid, Variofill®, in patients affected by bilateral knee osteoarthritis in comparison with the widely used Synvisc®. A total of 20 patients, aged between 24–74 years and affected by bilateral knee osteoarthritis, participated in this pilot randomized triple-blind clinical study. They received two injections (2 ml each) of Synvisc® in their left knee and 2 injections (2 ml each) of Variofill® in their right knee spaced 15 days apart. Visual Analogue Scale and Western Ontario McMaster Universities Osteoarthritis Index score were used to evaluate the efficacy of hyaluronic acid injections before and 3 and 6 months after treatment. Both treatment regimens resulted in a significant improvement vs baseline in all endpoints at 3 and 6 months (p < 0.001). Treatment with Variofill® resulted in a high percentage improvement in Visual Analogue Scale pain, Western Ontario McMaster Universities Osteoarthritis Index score pain and physical activity, when compared to Synvisc® viscosupplementation, at 6 months (p < 0.05). These results are encouraging for larger clinical trials with Variofill® in larger cohorts of patients affected by osteoarthritis of the knee

Stem cells in clinical practice: applications and warnings

Stem cells are a relevant source of information about cellular differentiation, molecular processes and tissue homeostasis, but also one of the most putative biological tools to treat degenerative diseases. This review focuses on human stem cells clinical and experimental applications. Our aim is to take a correct view of the available stem cell subtypes and their rational use in the medical area, with a specific focus on their therapeutic benefits and side effects. We have reviewed the main clinical trials dividing them basing on their clinical applications, and taking into account the ethical issue associated with the stem cell therapy

Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid.

Osteoarthritis (OA), also called degenerative joint disease, is the most frequently occurring chronic musculoskeletal disease, particularly affecting the aging population. The use of viscosupplementation, i.e. intra-articular (IA) hyaluronic acid (HA) drug therapy, to treat OA, is growing worldwide, due to important results obtained from several clinical trials, which reported IA HA-related improvements in functional activity and pain management. This review is an update of the IA use of this compound in the treatment of OA, with clinical evidence from the last few years being discussed and used to delineate new trends for the future

High-power Magnetotherapy: A New Weapon in Urinary Incontinence?

Objective: Urinary incontinence (UI) is one of the most common urinary system diseases that mostly affects women but also men. We evaluated the therapeutic efficacy of functional magnetic stimulation (FMS) as potential UI treatment with improvements in the pelvic floor musculature, urodynamic tests and quality of life. Methods: A total of 20 UI patients (10 females and 10 men, mean age 64, 14 years), including 10 with stress UI, four with urgency UI and six with mixed UI, were treated with FMS (20 min/session) twice a week for 3 weeks. The patients\u2019 impressions, records in urinary diaries, and scores of three life stress questionnaires (overactive bladder symptom questionnaire [OAB-q], urogenital distress inventory questionnaire-short form [UDI-6], incontinence impact questionnaire-short form [IIQ-7]) were performed pre- and post-treatment. Results: Significant reductions (P &lt; 0.01) of micturition number and nocturia after magnetic treatment were evi- denced. The urodynamic tests recorded a significant increase in cystometric capacity (147 \ub1 51.3%), in maximum urethral closure pressure (110 \ub1 34%), in urethral functional length (99.8 \ub1 51.8%), and in pressure transmission ratio (147 \ub1 51.3%) values compared with the baseline values. Conclusions: These preliminary findings suggest that FMS with Magneto STYM (twice weekly for 3 weeks) improves the UI and may be an effective treatment for this urogenital disease

A Preliminary Clinical Study

Background. Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. Aim. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapic injections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. Materials and Methods. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. Patients were preliminarily submitted to echo color Doppler sonography to rule out severe saphenofemoral valve and lower limb major vein insufficiency. All patients underwent 3 sessions a month of polidocanol 1% capillary injections for 2 months. This was followed by 0.1 ml cross-linked hyaluronic acid introduction in the polidocanol 1% needle track. A total of 50 mesotherapic injections (0.05 ml each) were performed on the skin surface where an ice pack was previously applied for 4 to 5 minutes. A follow-up visit was performed at 3 months. The results, based on photographic examination, were rated as follows: poor improvement (0%-50%), good improvement (51%-75%), and very good improvement (76%-100%). The side effects of the clinical procedure, in terms of pain, itching, paresthesia, ecchymosis, and relapse of telangiectasia over the treated skin surface, as well as a persisting pigmentation in the injection spots and induced benefits related to leg heaviness and comfort, were recorded. Results. In total, 6 patients displayed a slight venous insufficiency, 3 patients displayed patent venous insufficiency, and 11 patients did not show any venous insufficiency. Before treatment, itching was present in 18 out of 20 patients, paresthesia in 15 out of 20 patients, ecchymosis in 16 out of 20 patients, and leg heaviness in 15 out of 20 patients. At the 3-month follow-up, an improvement of 0% to 50% was observed in 4 patients who had a relapse in telangiectasia. A 51% to 75% improvement was observed in 3 patients and a 76% to 100% improvement occurred in 13 patients. At the 3-month follow-up, itching persisted only in 4 patients; paresthesia was absent in 12 patients, while 3 patients still presented this symptom; ecchymosis was absent in 16 patients; 15 patients reported a feeling of lightweight legs. Among the patients with relapsing telangiectasia, 2 patients reported pigmentation due to hemosiderin deposit in the skin at the 3-month follow-up. The slight venous insufficiency, observed at the beginning of the study, improved in 5 out of 6 patients. The patients' compliance with the procedure was high and 16 out of 20 patients declared their willingness to repeat the whole clinical procedure, if necessary. Conclusions. This pilot clinical study supports the use of hyaluronic acid mesotherapic injections following sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency. We propose that the prolonged persistence of cross-linked hyaluronic acid, across the microvascular venous areas, is able to induce a stronger stromal tissue, thus preventing relapse. Further clinical studies, comparing this new approach with existing clinical procedures, are needed in a larger number of patients

Combination Therapy of Hyaluronic Acid Mesotherapic Injections and Sclerotherapy for Treatment of Lower Leg Telangiectasia Without Major Venous Insufficiency: A Preliminary Clinical Study

Background. Telangiectasia is the dilation of dermal capillaries mainly due to hypertension and vein insufficiency. Treatments of choice for this condition are sclerotherapy with foam liquid or intradermal fiber optic laser energy delivery. Aim. The aim of this study was to assess the efficacy of a new therapeutic approach consisting in the use of polymerized hyaluronic acid mesotherapicinjections following sclerotherapy in the areas of the skin affected by telangiectasia in patients without major vein insufficiency. Materials and Methods. A total of 20 women, aged between 19 and 64 years, affected by recurrent lower leg telangiectasia, were included in this study. Patients were preliminarily submitted to echo color Doppler sonography to rule out severe saphenofemoral valve and lower limb major vein insufficiency. All patients underwent 3 sessions a month of polidocanol 1% capillary injections for 2 months. This was followed by 0.1 ml cross-linked hyaluronic acid introduction in the polidocanol 1% needle track. A total of 50 mesotherapic injections (0.05 ml each) were performed on the skin surface where an ice pack was previously applied for 4 to 5 minutes. A follow-up visit was performed at 3 months. The results, based on photographic examination, were rated as follows: poor improvement (0%-50%), good improvement (51%-75%), and very good improvement (76%-100%). The side effects of the clinical procedure, in terms of pain, itching, paresthesia, ecchymosis, and relapse of telangiectasia over the treated skin surface, as well as a persisting pigmentation in the injection spots and induced benefits related to leg heaviness and comfort, were recorded. Results. In total, 6 patients displayed a slight venous insufficiency, 3 patients displayed patent venous insufficiency, and 11 patients did not show any venous insufficiency. Before treatment, itching was present in 18 out of 20 patients, paresthesia in 15 out of 20 patients, ecchymosis in 16 out of 20 patients, and leg heaviness in 15 out of 20 patients. At the 3-month follow-up, an improvement of 0% to 50% was observed in 4 patients who had a relapse in telangiectasia. A 51% to 75% improvement was observed in 3 patients and a 76% to 100% improvement occurred in 13 patients. At the 3-month follow-up, itching persisted only in 4 patients; paresthesia was absent in 12 patients, while 3 patients still presented this symptom; ecchymosis was absent in 16 patients; 15 patients reported a feeling of lightweight legs. Among the patients with relapsing telangiectasia, 2 patients reported pigmentation due to hemosiderin deposit in the skin at the 3-month follow-up. The slight venous insufficiency, observed at the beginning of the study, improved in 5 out of 6 patients. The patients’ compliance with the procedure was high and 16 out of 20 patients declared their willingness to repeat the whole clinical procedure, if necessary. Conclusions. This pilot clinical study supports the use of hyaluronic acid mesotherapic injections following sclerotherapy for treatment of lower leg telangiectasia without major venous insufficiency. We propose that the prolonged persistence of cross-linked hyaluronic acid, across the microvascular venous areas, is able to induce a stronger stromal tissue, thus preventing relapse. Further clinical studies, comparing this new approach with existing clinical procedures, are needed in a larger number of patients