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Introduction & Objectives: Treatment with daylight photodynamic therapy (dPDT) of actinic keratosis (AK) is associated with local skin reactions (LSR), which may affect patients' quality of life and treatment acceptability. This study explores the potential of a prebiotic and panthenol-containing Dermocosmetic Cream (DC) to enhance tolerance and mitigate post-dPDT induced LSR in the treatment of AKs., Materials & Methods: This randomized controlled, intra-individual trial included 20 patients with ≥10 AKs in two symmetrical areas on their face or décolleté, treated with a single session of artificial dPDT. After treatment, the two areas were randomized to DC twice daily for 14 days or No-DC. Primary outcomes included clinical signs of LSR graded from 0=none to 3=severe, calculated as a composite score, and assessed on Days 2, 7, 14, and 30 post-treatment, along with AK clearance rate. Secondary outcomes encompassed objectively measured erythema, and clinical and objective skin photoaging assessment., Results: Topical application of DC following dPDT significantly improved post-treatment tolerance up to two weeks. By Day 2, DC-treated skin had milder LSR (median 3.0, IQR 2.0-4.8) compared to No-DC skin (median 4.0, IQR 3.0-5.0; p=0.011). This improvement continued on Day 7 (DC median 3.0, IQR 2.0-3.8 vs. No-DC median 4.5, IQR 3.0-5.8; p<0.001) and Day 14 (DC median 1.0, IQR 0.0-1.0 vs. No-DC median 1.0, IQR 1.0-2.0; p=0.004). Objective measurements showed milder erythema in DC-treated areas on Day 2 (p=0.045) and Day 7 (p=0.005). Crusting resolved more effectively in DC-treated areas by Day 7 (40% vs. 20%; p=0.039). No significant difference in complete lesion response rate was observed between DC and No-DC skin (p=0.850). By Day 30, clinical photoaging assessment demonstrated significant improvement in dyspigmentation (p=0.004) and skin texture (p<0.001) in both locations. Moreover, objective measurements revealed reduced dyspigmentation in both DC and No-DC treated skin (p≤0.001)., Conclusion: Application of a prebiotic and panthenol-containing multipurpose DC significantly enhanced tolerance from artificial dPDT and accelerated healing time up to 14 days after treatment. The use of DC cream did not affect the overall treatment efficacy of dPDT, indicating its potential to enhance patient comfort following dPDT., (Copyright © 2024. Published by Elsevier B.V.)

Background: Nowadays, moisturizers contain non-steroidal anti-inflammatory agents that help for treatment of atopic dermatitis (AD). Defensil® (black currant seed oil, sunflower oil, and balloon vine), a new anti-inflammatory, obtained from plant extracts, remain had a few studies for AD., Objective: To compare the effectiveness of moisturizer containing 3% Defensil®, 5% dexpanthenol and ceramide (LDC) with 5% urea cream in childhood AD treatment., Methods: Thirty-eight patients with diagnosis of atopic dermatitis by UK working party's criteria were recruited in randomized, controlled, double-blinded 4-week study. The patients were received with twice-daily application of LDC cream on one side of the body and 5% urea cream on the opposite side. The clinical severity was assessed by modified scoring of atopic dermatitis (SCORAD). Median time to remission was analyzed by survival analysis., Results: Thirty-seven out of 38 patients accomplished the protocol. The clinical SCORAD significantly improved from baseline in both groups (p < 0.001) after 2 and 4 weeks. Furthermore, the LDC group significantly reduced severity of disease better than the 5% urea group (P = 0.043). The mean difference SCORAD scores were -13.83 (±1.83) and -13.04 (±3.22) respectively. Stratum corneum hydration (SCH) was enhanced from baseline in both groups (p < 0.001) but no statistically significant difference between both groups. Median time to remission had no statistically significant difference (P = 0.697)., Conclusions: The effectiveness of LDC cream is better than 5% urea cream for improving clinical atopic dermatitis. It was suggested that moisturizer containing LDC could be used for the treatment of mild-to-moderate childhood atopic dermatitis.

Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA disorders. The diagnosis of PKAN is established with clinical features and the "eye of the tiger" sign identified on brain MRI and the identification of biallelic pantothenate kinase 2 (PANK2) pathogenic variants on molecular genetic testing. PANK2 catalyzes the first reaction of coenzyme A (CoA) biosynthesis, thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4'-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes., Methods: In this manuscript, we examined the effect of a multitarget complex supplements (pantothenate, pantethine, omega-3 and vitamin E) on in vitro patient-derived cellular models and the clinical outcome of the adjuvant supplements in combination with the baseline neurological medication in three PKAN patients., Results: Multitarget complex supplements significantly reduced iron accumulation and increased PANK2 and ACP expression levels in the cellular models derived from all three PKAN patients. In addition, the adjunct treatment to the standard neurological medication improved or stabilized the clinical symptoms of patients., Conclusions: Our results suggest that multitarget complex supplements can be clinically useful as augmentation therapy for PKAN patients harboring pathogenic variants with residual enzyme levels., Trial Registration: CAAE: 58219522.6.0000.5330. Registered 25 May 2022-Retrospectively registered, https://plataformabrasil.saude.gov.br/visao/pesquisador/gerirPesquisa/gerirPesquisaAgrupador.jsf ., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by The Ethical Committee of Hospital Universitario Virgen del Rocío and Virgen Macarena of Seville, protocol code BRAINCURE16, following the Spanish laws, the principles of the Declaration of Helsinki, and the Guideline for Good Clinical Practices; and by the Ethics Committee of Moinhos de Vento Hospital (CAAE: 58219522.6.0000.5330) and all the parents or legal guardians of subjects signed the written informed consent forms before any procedure was done. Consent for publication: Consent for publication were obtained from all parents or legal guardians. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Cheilitis is a chronic inflammatory condition of the lips, and frequent or prolonged use of topical corticosteroids may lead to various adverse events. Therefore, alternative therapies with fewer side effects are beneficial for the treatment of this condition., Aim: To evaluate the efficacy of a lip care formulation containing both panthenol and bisabolol as a monotherapy for mild-to-moderate cheilitis., Methods: This single-centre prospective pilot open-label study included 20 patients with mild-to-moderate cheilitis who were treated with the tested lip care for 8 weeks and evaluated by physician and patient assessments before the final efficacy was determined using the Visioscan score., Results: Of the 20 patients, 13 (65.0%) presented with moderate cheilitis with dry and chapped lips. All parameters, including physician and patient clinical scores and bioengineering measurements, showed significant improvements as early as week 2 and sustained until week 8 following the application of the tested lip care. The frequency of cheilitis flareups also decreased significantly. The tested product was well tolerated without any adverse effects., Conclusions: Lip care with panthenol and bisabolol was safe and effective. It can be used as monotherapy for the treatment of mild-to-moderate cheilitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of this pathology., Material and Methods: A total of 90 children aged 8 to 10 years were examined. Of these, the main study group consisted of 30 children with NCT, the comparison group consisted of 30 children with a combined type of attention deficit hyperactivity disorder ADHD (ADHD-K), the control group consisted of 30 children without neuropsychiatric disorders. The study used clinical, neurophysiological (electroencephalography (EEG)) and parametric methods. The CMAS scale of apparent anxiety (The Children's Form of Manifest Anxiety Scale), the SNAP-IY scale (assessment of the degree of inattention, hyperactivity and impulsivity), the TOVA computer test (the Test of Variables of Attention), the scale «SCT» (Sluggish Cognitive Tempo) for assessing manifestations of low cognitive tempo, the «RAM» technique for quantifying working memory. Pantogam was used to treat patients at a dose of 750 mg per day for 8 weeks., Results: Patients with NCT are characterized by more pronounced attention disorders compared with healthy peers and with children with ADHD-K, and they have a decrease in mainly not selective attention, but the overall level of functional activity. Also, the group of children with NCT has an increased level of anxiety compared to the group of children with ADHD. A comparative analysis of the level of impulsivity showed that children with NCT are less characterized by a deficit in inhibition processes. According to the quantitative analysis of the EEG, specific changes in functional activity in the frontal and central regions of the cerebral cortex were revealed (a statistically significant increase in the ratio of absolute theta rhythm to beta1 rhythm, compared with other groups), reflecting insufficient cortical arousal and less focused neural states. When re-evaluating the condition of children with NCT after a course of therapy with Pantogam, an improvement in the form of a decrease in the degree of inattention, the severity of memory impairment and a decrease in reaction time was recorded in 60% of cases. According to quantitative EEG analysis, there was a significant decrease in the ratio of absolute theta rhythm to beta1 rhythm in the central leads of both hemispheres and in the parietal-temporal leads of the left hemisphere, indicating an increase in the level of overall activation of the cerebral cortex after a course of treatment., Conclusion: Clinical and neurophysiological differences were revealed in patients with NCT and with combined ADHD. It has been shown that the use of Pantogam for the treatment of children with NCT leads not only to a decrease in the main manifestations of this disorder, but also to an improvement in the functional state of the brain.

Doxorubicin (DOX), which is used as a chemotherapeutic agent in the treatment of tumors, has limited use due to its toxicity in various organs and tissues. One of the organs where DOX has a toxic effect is the lung. DOX shows this effect by increasing oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a homologue of pantothenic acid, has anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, the purpose of our investigation was to explore how DEX could counteract the harmful effects of DOX on the lungs. Thirty-two rats were used in the study, and 4 groups were formed (control, DOX, DOX + DEX, and DEX). In these groups, parameters of inflammation, ER stress, apoptosis, and oxidative stress were evaluated by immunohistochemistry, RT-qPCR, and spectrophotometric methods. In addition, lung tissue was evaluated histopathologically in the groups. While CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions increased in the DOX group, Bcl-2 gene expression levels significantly decreased. In addition, changes in Bax and Bcl-2 were supported immunohistochemically. There was a significant increase in oxidative stress parameters and a significant decrease in antioxidant levels. In addition, an increase in inflammatory marker (TNF-α and IL-10) levels was determined. There was a decrease in CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions and an increase in Bcl-2 gene expression in the DEX-treated group. In addition, it was determined that there was a decrease in oxidative stress levels and inflammatory findings. The curative effect of DEX was supported by histopathological findings. As a result, it was experimentally determined that DEX has a healing effect on oxidative stress, ER stress, inflammation, and apoptosis in lung damage caused by DOX toxicity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Issues of regeneration of the cornea, which is the most vulnerable structure of the eyeball, suffering from various diseases and injuries, burns, when wearing contact lenses and glaucoma, are highly relevant for ophthalmologists. It is also necessary to minimize damage and stimulate corneal epithelization during and after the use of steroidal and non-steroidal anti-inflammatory drugs, antibacterial drugs and antiseptics, which have a cytotoxic effect and often inhibit regeneration processes, potentially even leading to the development of corneal epithelial defects. This review analyzes the effectiveness of a promising drug 5% dexpanthenol in terms of improving the reparative processes and the function of epithelial cells.

Combination therapy with biotin and dexpanthenol is a well-known practice in preventing and treating hair loss, however, it is not well studied. In this study, we compared the efficacy of the 6-week treatment with two brands of biotin and dexpanthenol for the treatment of diffuse hair loss. Fifty eligible patients with diffused pattern hair loss, (41 women and 9 men) were randomized in a 1:1 ratio to receive either 6 weekly injections of dexpanthenol ampoule 250 mg/2 ml and biotin ampoule 5 mg/1 ml, manufactured by Pars Behvarzan or Bayer Company. Combing test, Standard scalp photography and trichoscan assessment were performed before the first treatment session and one and 8 weeks after the last one. Patients' satisfaction and drug adverse reactions were also recorded. One and eight weeks after the last treatment session, hair fall count and total hair density significantly improved in both groups (p-value <0.01 for hair fall count and 0.04 and 0.02, for hair density in Pars and Bayer groups, respectively). There was no significant difference between the two groups in any other trichoscan parameter, except for improvement in terminal/vellus hair ratio in the Bayer group in both follow up visits, compared to the Pars group (p-value = 0.02 and 0.033 for weeks one and eight). Six-week treatment with both brands of biotin and dexpanthenol was effective and safe in people with diffused pattern hair loss., (© 2022 Wiley Periodicals LLC.)

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study aimed to investigate the molecular effects of radiation and subsequent aftercare treatment with dexpanthenol-containing ointment and liquid on established full-thickness 3D skin models depicting acute radiodermatitis and mucositis. To mimic radiomucositis and radiodermatitis, non-keratinized mucous membrane and normal human skin models were irradiated with 5 Gray. Afterwards, models were treated topically every second day with dexpanthenol-containing ointment or liquid in comparison with placebo and untreated controls. On day 7 after irradiation, histological examination showed impairments in irradiated models. In contrast, models treated with dexpanthenol-containing ointment or liquid showed a completely restored epidermal part. While gene expression profiling revealed an induction of genes related to a pro-inflammatory milieu, oxidative stress and an impaired epidermal differentiation after irradiation of the models, aftercare treatment with dexpanthenol-containing ointment or liquid revealed anti-oxidative and anti-inflammatory effects and had a positive effect on epidermal differentiation and structures important for physical and antimicrobial barrier function. Our findings confirm the potential of our established models as in vitro tools for the replacement of pharmacological in vivo studies regarding radiation-induced skin injuries and give indications of the positive effects of dexpanthenol-containing externals after radiation treatments as part of supportive tumor treatment., (© 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Malaria-causing Plasmodium parasites are developing resistance to antimalarial drugs, providing the impetus for new antiplasmodials. Although pantothenamides show potent antiplasmodial activity, hydrolysis by pantetheinases/vanins present in blood rapidly inactivates them. We herein report the facile synthesis and biological activity of a small library of pantothenamide analogues in which the labile amide group is replaced with a heteroaromatic ring. Several of these analogues display nanomolar antiplasmodial activity against Plasmodium falciparum and/or Plasmodium knowlesi , and are stable in the presence of pantetheinase. Both a known triazole and a novel isoxazole derivative were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro . Although they fail to suppress Plasmodium berghei proliferation in vivo , the pharmacokinetic and contact time data presented provide a benchmark for the compound profile likely required to achieve antiplasmodial activity in mice and should facilitate lead optimization.

Post-acne hyperpigmentation (PAH) occurs secondary to acne vulgaris and may cause significant adverse effects. Although may occur in any skin types, PAH has been found to be more common and severe in people with colored skin. This study aimed to assess the effectiveness of combination serum containing galactomyces ferment filtrate (GFF), dexpanthenol, and Centella asiatica for treating PAH. This randomized controlled clinical trial involved Fitzpatrick skin type (FST) IV and V patients with PAH. Subjects were equally divided into treatment group, who received three drops of combination serum twice daily for 8 weeks, and placebo group. The melanin index (MI) and Lightness (L*) score were assessed every 2 weeks. Out of 51 subjects, the L* score of the treatment group in subjects with FST V was significantly higher on the 4th and 6th week compared to the placebo group ( P ˂ 0.05). The MI of subjects with FST IV was significantly lower compared to the placebo group after 8 weeks ( P ˂ 0.05). The treatment group showed consistent increasing and decreasing trend in L* score and MI, respectively ( r ˃ 0.9, P ˂ 0.05). Combination serum containing GFF, dexpanthenol, and C. asiatica may be effective in treating PAH in subjects with colored skin by accelerating lessening of PAH.

Mutations in the human PANK2 gene are implicated in neurodegenerative diseases such as pantothenate kinase-associated neurodegeneration (PKAN) and result in low levels of coenzyme-A (CoA) in the CNS due to impaired production of phosphopantothenic acid (PPA) from vitamin B5. Restoration of central PPA levels by delivery of exogenous PPA is a recent strategy to reactivate CoA biosynthesis in PKAN patients. Fosmetpantotenate is an oral PPA prodrug. We report here the development of a new PANk2 -/- knockout model that allows CoA regeneration in brain cells to be evaluated and describe two new series of cyclic phosphate prodrugs of PPA capable of regenerating excellent levels of CoA in this system. A proof-of-concept study in mouse demonstrates the potential of this new class of prodrugs to deliver PPA to the brain following oral administration and confirms incorporation of the prodrug-derived PPA into CoA.

Objective: Limited data exist on the clinical benefits of nasal applications for moistening the nasal mucosa. We therefore investigated the effects of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms in an otorhinolaryngological outpatient setting., Methods: 240 patients were randomised into this prospective, three-armed clinical trial with two assessment points (baseline and 4 weeks later). Patients received either hyaluronic acid, hyaluronic acid plus dexpanthenol or isotonic saline nasal spray over a period of four weeks. Rhinitis Sicca Symptom Score (RSSS) was assessed as primary endpoint, and individual symptoms and tolerability of all treatments as secondary endpoints. Patient perceptions after first application of the allocated nasal spray were recorded using the Nasal Spray Sensory Scale. Treatment effects were analysed for each study arm first and subsequently compared against each other., Results: RSSS (hyaluronic acid: mean difference = 8.90 [98.33% CI = 7.34/10.45]; hyaluronic acid plus dexpanthenol: mean difference = 8.42 [98.33% CI = 6.91/9.94]; isotonic saline: mean difference = 8.94 [98.33% CI = 7.33/10.54]), individual symptoms and Endoscopy Score improved significantly (p < 0.001) in all treatment arms. Tolerability was assessed as "flawless" in more than 85% of all treatments, which is reflected in overall high rankings in the Nasal Spray Sensory Scale. Perception of nasal moisturisation was reported to be significantly higher in patients receiving hyaluronic acid plus dexpanthenol as compared to patients receiving hyaluronic acid or isotonic saline. No further significant differences were observed between the three treatments., Conclusion: All three tested sprays (hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline) proved to be suitable treatments for patients suffering from dry nose symptoms. (DRKS-ID: DRKS00013357)., Competing Interests: Declaration of Competing Interest The trial was funded by URSAPHARM Arzneimittel GmbH. Peter Meiser is employed at URSAPHARM Arzneimittel GmbH. The authors have declared that there is no further financial support or relationship that may pose a conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN., Methods: Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500 mg/kg for 5 days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10 mg/kg), tenoxicam (0.5 mg/kg) and sodium amidotrizoate (10 ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected., Results: When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels., Conclusions: Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.

Background/aims: Pantothenate kinase-associated neurodegeneration is a rare neurodegenerative disease with a variable clinical phenotype. Fosmetpantotenate is in clinical development as a replacement therapy that targets the underlying cause of pantothenate kinase-associated neurodegeneration. The FOsmetpantotenate Replacement Therapy pivotal trial-an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter trial-examines the efficacy and safety of fosmetpantotenate in patients with pantothenate kinase-associated neurodegeneration aged 6-65 years. The FOsmetpantotenate Replacement Therapy trial required the development and validation of a novel patient-reported outcome measure specifically relevant to pantothenate kinase-associated neurodegeneration. The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to assess activities of daily living related to motor functioning in patients with pantothenate kinase-associated neurodegeneration to evaluate clinically meaningful change as the primary efficacy endpoint in clinical trials. This article describes the design of the FOsmetpantotenate Replacement Therapy pivotal trial and the development of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale., Methods: A systematic, iterative process consistent with the US Food and Drug Administration guidance and advice from the Committee for Medicinal Products for Human Use at the European Medicines Agency was used to evaluate and adapt or remove scale items of an existing widely used instrument for movement disorders to be pantothenate kinase-associated neurodegeneration-specific, and to create new items. Modification of scale items was based on input from international experts, patient advocacy leaders, and primary caregivers. A clinimetric study of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale conducted in patients with pantothenate kinase-associated neurodegeneration or their caregivers (N = 40 at first assessment; N = 39 at second assessment) demonstrated high content and construct validity and excellent test-retest reliability over an approximately 2-week period. The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale was developed to be broadly useful within clinical and research settings in the examination of patient response to pantothenate kinase-associated neurodegeneration therapies., Results: Approximately 82 patients will be enrolled in the ongoing FOsmetpantotenate Replacement Therapy pivotal trial. Change from baseline in Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living score over the 24-week double-blind period is the primary efficacy endpoint for the FOsmetpantotenate Replacement Therapy trial. Treatment effect will be evaluated using a mixed model for repeated measures analysis to assess data from all visits simultaneously., Conclusion: The development and implementation of the Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living scale in the FOsmetpantotenate Replacement Therapy trial illustrates the feasibility and potential patient benefit of putting into practice the current regulatory guidance on the use of patient-reported outcomes in clinical trials. These processes can be broadly applied to clinical trial methodology that requires newly created or revised patient-reported outcome measures to evaluate outcome change as a primary efficacy endpoint. The goal of such measures in patients with pantothenate kinase-associated neurodegeneration is to facilitate development of disease-modifying therapeutics in multiple drug development programs.

Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pantothenate in particular mutations was also confirmed in induced neurons obtained by direct reprograming of mutant fibroblasts. Our results suggest that pantothenate treatment can stabilize the expression levels of PANK2 in selected mutations. These results encourage us to propose our screening model as a quick and easy way to detect pantothenate-responder patients with PANK2 mutations. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of pantothenate.

Background: Postoperative complications occur after periodontal plastic surgeries, but an ideal treatment to overcome them has not been found yet., Aims: To evaluate the effects of topically applied Oral-norm gel on the healing of excisional wounds., Study Design: Animal experiment., Methods: Excisional wounds with a diameter of 3 mm were made in the center of the palatal mucosa of 63 Sprague Dawley rats. Seven animals were sacrificed at time 0. The remaining rats were divided into two groups: a test group in which the topical Oral-norm gel was applied three times a day and a control group in which nothing was applied. Seven animals in each group were sacrificed at 3, 7, 14, and 21 days. Mean wound surface area was measured photographically, while wound healing and width were evaluated microscopically., Results: The mean wound surface area decreased significantly after 3 days in both groups (p<0.001). Between days 3 and 7, the mean wound surface area decreased from 6.62 (2.85) to 0.83 (1.62) mm 2 in the control group and 5.07 (0.88) to 1.42 (1.67) mm 2 in the test group. The wound width decreased significantly on day 7 in both groups (p<0.001), with no further changes by day 14. Both groups had a significant increase in inflammation and vascularization on day 3 (p<0.001), with a reduction thereafter. No significant differences in macroscopic and microscopic measurements were observed between the groups at any time point (p>0.05)., Conclusion: The Oral-norm gel has no positive healing effects in the palatal mucosa of rats.

Aim: To evaluate the efficacy and safety of hopantenic acid (Pantogam) in the complex treatment of prematurely born infants, aged 6-12 months, with psychomotor developmental delay due to hypoxic-ischemic encephalopathy., Material and Methods: Eighty-seven patients were randomized into two groups: 44 received standardized treatment and pantogam for two months, 43 standardized treatment and placebo. Pantogam (syrup 100 mg/ml) or placebo were prescribed orally 15-30 minutes after feeding, twice a day, in a daily dosage of 30-50 mg/kg body weight. The assessment of psychomotor development from birth to two years was performed with the Griffiths Mental Development Scales (GMDS-ER) twice (before and after completion of therapy)., Results: The response to two month therapy determined as the reduction of developmental delay for more than 6% of the initial GMDS-ER general quotient (GQ) score was significantly better in the group I after pantogam treatment (63.6% of patients) compared to group II (36.4%, p=0.021). Group I demonstrated the significant decrease of the developmental delay in two domains ('Personal-Social' and 'Performance') and a trend to overcome the delay in three other domains: 'Locomotor', 'Hearing and Speech', 'Eye and Hand Coordination'. The improvement after pantogam treatment was more obvious in the subgroup of infants born late preterm (gestational age 34-36 weeks) compared to infants born moderate preterm (gestational age 32-33 weeks). The favorable safety profile of pantogam was confirmed, comparable to that of placebo., Conclusion: Pantogam is efficient and safe medication in the complex treatment of psychomotor developmental delay in preterm infants, aged 6-12 months.

Objective: We aimed to investigate the protective and therapeutic effects of dexpanthenol (DXP) on liver injuries induced by ischemia-reperfusion (IR) in an in vivo rat model., Methods: Thirty-two rats were randomly divided into 4 experimental groups (n = 8 in each group: Sham, IR, DXP, and DXP+IR. DXP (500 mg/kg) was intraperitoneally administered for 30 min before 60 min of ischemia, followed by 60 min of reperfusion to rats in the DXP and DXP+IR groups. All rats were euthanized on day 10 to evaluate immunohistopathological changes as well as tissue levels of oxidants and antioxidants., Results: IR decreased total glutathione (tGSH) levels in IR group when compared to the Sham group. DXP supplementation to IR group significantly ameliorated tGSH levels (P < .05). IR also elevated myeloperoxidase production compared to the Sham group, whereas DXP treatment prevented these hazardous effects. However, plasma superoxidedismutase, catalase, and malondialdehyde levels did not differ between the DXP+IR than the IR rats. Histologic tissue damage was reduced in the DXP and DXP+IR group., Conclusion: Liver IR is an inevitable problem during liver surgery. Our results suggested that DXP pretreatment suppressed oxidative stress and increased antioxidant levels in a rat model of liver IR., (Copyright © 2018. Published by Elsevier Inc.)

Introduction:  Analysis of data derived from homeopathic pathogenetic trials (HPTs, homeopathic drug provings) has been a challenge. Most parts of the homeopathic pharmacopeia were sourced from Hahnemann's Materia Medica Pura (1825-1833), TF Allen's Encyclopedia (1874) and Constantine Hering's Materia Medica (1879-1891), well before randomised controlled trials were in use. As a result, such studies and their outcomes harbour a large risk of inclusion of unreliable symptoms., Aims and Objective: The main purpose of this article is to introduce Quantitative and Qualitative Pathogenetic Indices to improve the method of analysis of symptoms., Materials and Methods:  The data from HPTs for human immunodeficiency virus nosode, hepatitis C nosode, capsaicin alkaloids (capsaicin and dihydrocapsaicin) and hydroquinone (HQ) were extracted and analysed in terms of novel Qualitative and Quantitative Pathogenetic Indices. Taken into the consideration were the qualitative aspect of a symptom (i.e. its intensity), and the quantitative aspect by calculating the number of symptoms per volunteer per day. The pathogenetic effects and data evaluation indices were calculated for each HPT. A comparison was made of symptoms of verum versus placebo provers in terms of their quantity and quality., Results:  Four HPTs involving 81 volunteers (56 on verum and 25 on placebo) generated 555 symptoms or pathogenetic effects (excluding run-in phase symptoms), of which 448 (81%) were reported by volunteers who were in the verum arm, and 107 (19%) were reported by volunteers on placebo. The overall mean incidence of pathogenetic effects for the four HPTs was thus 8 per verum prover and 4.28 per placebo prover. The corresponding mean Quantitative Pathogenetic Index was 0.23 symptoms per volunteer per day for the verum arm and 0.12 symptoms per volunteer per day for the placebo arm. The overall mean incidence of pathogenetic effects in the run-in phase was less. The overall mean Qualitative Pathogenetic Index (number of symptoms, of a given intensity, per volunteer per day) for the verum arm was 0.09 versus 0.05 for the placebo arm., Conclusion:  The symptoms exhibited by volunteers in the verum arm were more numerous and more intense than those in the placebo arm. An innovative and logical method of reporting of symptoms and analysis has been introduced by the use of these pathogenetic indices, which can be used in future as measurement tools for analysis of data from HPTs., Competing Interests: None., (The Faculty of Homeopathy.)

The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO 2 ), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase-3 were determined. BP and SO 2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO-induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity., (© 2018 Wiley Periodicals, Inc.)

The objective of our research was histological evaluation of therapeutic effects in case of burn injury in rats. Experiment was conducted on 84 test rats with burn injury of III-A stage. Therapeutical effect of studied medicines was evaluated using histological methods. Results achived gave evidence that on 18-th day of treatment with ceremids cream and dexpanthenol with ceramids cream the level granulation tissue maturing increased by 1,4 and 1,7 times and intensity of burn injury epithelization rose by 1,5 and 1,9 times in comparison with non-treated animals. Therapeutic effect of dexpanthenol with ceramids cream significantly overcome action of «Bepanten» cream. Thus, experiment done proved efficiency of ceramids use in cream composition with dexpanthenol as one of the therapeutic methods aimed at increase of skin burn injury healing activation.

Importance: Surveys of patients with multiple sclerosis report that most are interested in modifying their diet and using supplements to potentially reduce the severity and symptoms of the disease. This review provides an updated overview of the current state of evidence for the role that vitamins and dietary supplements play in multiple sclerosis and its animal models, with an emphasis on recent studies, and addresses biological plausibility and safety issues., Observations: Several vitamins and dietary supplements have been recently explored both in animal models and by patients with multiple sclerosis. Most human trials have been small or nonblinded, limiting their generalizability. Biotin and vitamin D are currently being tested in large randomized clinical trials. Smaller trials are ongoing or planned for other supplements such as lipoic acid and probiotics. The results of these studies may help guide clinical recommendations., Conclusions and Relevance: At the present time, the only vitamin with sufficient evidence to support routine supplementation for patients with multiple sclerosis is vitamin D. Vitamin deficiencies should be avoided. It is important for clinicians to know which supplements their patients are taking and to educate patients on any known efficacy data, along with any potential medication interactions and adverse effects of individual supplements. Given that dietary supplements and vitamins are not subject to the same regulatory oversight as prescription pharmaceuticals in the United States, it is recommended that vitamins and supplements be purchased from reputable manufacturers with the United States Pharmacopeia designation.

In cells, phosphorylation of pantothenic acid to generate phosphopantothenic acid by the pantothenate kinase enzymes is the first step in coenzyme A synthesis. Pantothenate kinase 2, the isoform localized in neuronal cell mitochondria, is dysfunctional in patients with pantothenate kinase-associated neurodegeneration. Fosmetpantotenate is a phosphopantothenic acid prodrug in clinical development for treatment of pantothenate kinase-associated neurodegeneration, which aims to replenish phosphopantothenic acid in patients. Fosmetpantotenate restored coenzyme A in short-hairpin RNA pantothenate kinase 2 gene-silenced neuroblastoma cells and was permeable in a blood-brain barrier model. The rate of fosmetpantotenate metabolism in blood is species-dependent. Following up to 700 mg/kg orally, blood exposure to fosmetpantotenate was negligible in rat and mouse, but measurable in monkey. Consistent with the difference in whole blood half-life, fosmetpantotenate dosed orally was found in the brains of the monkey (striatal dialysate) but was absent in mice. Following administration of isotopically labeled-fosmetpantotenate to mice, ~40% of liver coenzyme A (after 500 mg/kg orally) and ~50% of brain coenzyme A (after 125 μg intrastriatally) originated from isotopically labeled-fosmetpantotenate. Additionally, 10-day dosing of isotopically labeled-fosmetpantotenate, 12.5 μg, intracerebroventricularly in mice led to ~30% of brain coenzyme A containing the stable isotopic labels. This work supports the hypothesis that fosmetpantotenate acts to replace reduced phosphopantothenic acid in pantothenate kinase 2-deficient tissues.

The goal of the present study was to develop a new intramammary combination preparation for veterinary use based on silver citrate, arginine and dexpanthenol for the treatment and prophylaxis of subclinical mastitis in cattle. When creating combined medicines for veterinary use, attention must be paid to the factors that influence their stability in a combined presence, and the composition of drugs, as well as the technology for their preparation should be determined. In the current study, a qualitative and quantitative control of model mixtures of active ingredients, as well as of a silver citrate-based combined preparation was carried out. The following parameters that define intramammary drug stability were studied: clarity, pH, and the quantitative content of the active ingredient. Based on the experimental studies, optimal pH limits for a new preparation were determined ranging from 6.4 to 6.7. Considering the instability of solutions based on silver citrate, studies on the stabilization of the preparation were conducted at the obtained pH values. As the result, we used povidone, which possessed the stabilizing properties. The amount of arginine that provides the optimum pH level for the selected combination of active ingredients was also determined. In conclusion, the optimal composition of an intramammary preparation for veterinary medicine in 10 ml ampoules with a shelf life of 6 months was developed.Key words: silver citrate arginine dexpanthenol intramammary dosage form stability.

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5's promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4 + T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4 + and CD8 + T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.

Introduction: Predictive in vitro testing of novel wound therapeutics requires adequate cell-based bio-assays. Such assays represent an integral part during preclinical development as pre-step before entering in vivo studies. Simple "scratch tests" based on defected skin cell monolayers exist, however these can solely be used for testing liquids, as cell monolayer destruction and excessive hydration limit their applicability for (semi-)solid systems like wound dressings. In this context, a cell-based wound healing assay is introduced for rapid and predictive testing of wound therapeutics independent of their physical state in a bio-relevant environment., Methods: A novel wound healing assay was established for bio-relevant and predictive testing of (semi-) solid wound therapeutics., Results: The assay allows for physiologically relevant hydration of the tested wound therapeutics at the air-liquid interface and their removal without cell monolayer disruption. In a proof-of-concept study, the applicability and discriminative power could be demonstrated by examining unloaded and drug-loaded wound dressings with two different established wound healing actives (dexpanthenol and metyrapone) and their effect on skin cell behavior. The influence of the released drug on the cells´ healing behavior could successfully be monitored over time. Wound size assessment after 96h resulted in an eight fold smaller wound area for drug treated models compared to the ones treated with unloaded fibers and non-treated wounds., Discussion: This assay provides valuable first insights towards the establishment of a valid screening and evaluation tool for preclinical wound therapeutic development from liquid to (semi-)solid systems to improve predictability in a simple, yet standardized way., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Essential arterial hypertension (AH) is one of the main risk factors for the development of cognitive impairment and dementia. Cognitive decline is an early sign of brain damage as a target organ of hypertension, it occurs even in patients with uncomplicated hypertension with minimal duration of disease. Cognitive impairment progresses with increasing age and hypertension duration, as well as in non-controlled AH. In patients with hypertension, the prevalence of emotional disorders - anxiety and depression is also high. In addition to antihypertensive therapy, hypertensive patients need correction of concomitant cognitive and emotional disorders. Rat-gopantenic acid simultaneously corrects both emotional and cognitive impairment, and has a good tolerability profile as well. An analysis of the evidence base of rac-gopantenic acid showed its high efficacy in the treatment of mental disorders and good tolerability along with a positive effect on somatic disorders and results of antihypertensive therapy. Taken together, they enhance adherence to treatment and, consequently, reduce the cardiovascular risk.

Approximately 70 years ago, the first topical dexpanthenol-containing formulation (Bepanthen™ Ointment) has been developed. Nowadays, various topical dexpanthenol preparations exist, tailored according to individual requirements. Topical dexpanthenol has emerged as frequently used formulation in the field of dermatology and skin care. Various studies confirmed dexpanthenol's moisturizing and skin barrier enhancing potential. It prevents skin irritation, stimulates skin regeneration and promotes wound healing. Two main directions in the use of topical dexpanthenol-containing formulations have therefore been pursued: as skin moisturizer/skin barrier restorer and as facilitator of wound healing. This 70th anniversary paper reviews studies with topical dexpanthenol in skin conditions where it is most frequently used. Although discovered decades ago, the exact mechanisms of action of dexpanthenol have not been fully elucidated yet. With the adoption of new technologies, new light has been shed on dexpanthenol's mode of action at the molecular level. It appears that dexpanthenol increases the mobility of stratum corneum molecular components which are important for barrier function and modulates the expression of genes important for wound healing. This review will update readers on recent advances in this field.

Objective: To investigate the effect of dexpanthenol-vitamin A (Nazalnem) ointment applied to the surface of silastic splints with an airway immediately after nasal septal surgery on postoperative complaints and nasal mucosa function., Materials and Methods: The study enrolled 60 patients undergoing nasal septoplasty surgery. Group 1 (n = 30) received silastic splints with ointment containing dexpanthenol-vitamin A (Nazalnem), and Group 2 (n = 30), the control group, received silastic splints with vaseline. Of these patients, 2 patients from the Group 1 and 9 from the Group 2 were excluded.A thin layer of ointment was applied to the flat side of a silastic splint with an airway. The splints were removed on the second postoperative day. Patients were evaluated preoperatively and 1 and 2 weeks postoperatively using a visual analog scale and the Sino-Nasal Outcome test (SNOT-22). Mucociliary clearance (MCC) tests were performed at the same times., Results: Visual analog scale for nasal crusting, nasal congestion, and foul odor was better in Group 1 than in Group 2 both at 1 week and at 2 weeks postoperatively (P < 0.05).The SNOT scores were significantly lower in Group 1 than in Group 2 at 1 week (P < 0.01), but did not differ at 2 weeks postoperatively (P > 0.05).Postoperatively, the MCC were insignificant between the groups and within the groups at 1 and 2 weeks (P > 0.05)., Conclusion: Although Dexpanthenol-Vitamin A ointment had no direct effect on wound healing, it had significant effects on crusting, obstruction, and foul smell. However, silastic splints with dexpanthenol did not improve the MCC of the nose.

Purpose: Radiotherapy-induced moist desquamation (RIMD) is a complication that can affect patients' quality of life and jeopardize radiotherapy outcomes. The curative use of a hydroactive colloid gel has previously been shown effective in the management of RIMD in breast cancer patients. This study aimed at investigating the efficacy of this same gel but in the prevention of RIMD., Methods: A group of breast cancer patients who applied the hydroactive gel from start to end of post-lumpectomy radiotherapy (Preventive Hydrogel group) were compared with two groups of matched historical controls: a group applying a dexpanthenol cream throughout their therapy and a group applying first the dexpanthenol cream then, after 11-14 fractions of radiotherapy, the hydroactive gel (Curative Hydrogel group). All patients received identical fractionation regimen. The clinical outcomes were the incidence and time to onset of RIMD., Key Results: After 25 fractions of radiotherapy (50 Gy), patients in the Preventive Hydrogel group (N = 202) developed RIMD significantly less frequently and later than patients in the Dexpanthenol group (N = 131; incidence = 7% vs 35% respectively, odds ratios = 7.27; probability of RIMD-free survival after 50 Gy = 0.88 vs 0.62). There were no significant differences between the Preventive and the Curative Hydrogel group (N = 87)., Conclusions: These findings confirm our previous results: applying the hydroactive colloid gel, rather than dexpanthenol, delayed the onset and reduced the incidence of RIMD in breast cancer patients. However, applying the hydrogel preventively offered no statistically significant advantages over applying it curatively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the effect of two different doses of dexpanthenol (Dxp) onexperimentally induced ovarian ischaemia/reperfusion (I/R) injury ina rat model., Study Design: Forty female rats were randomly divided into fivegroups: Group 1: sham operation; Group 2: 3-h ischaemia; Groups 3: 3-h ischaemia, 3-h reperfusion (I/R); Group 4: I/R + 300 mg/kg Dxp intraperitoneally (i.p) Group 5: I /R + 500 mg/kg Dxpi.p. Total anti-oxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), tissue malondialdehyde (MDA) and activities of glutathione peroxidase and catalase were calculated. Ovarian tissue damage was assessed using a histopathological scoring system., Results: The TOS and OSI values were significantly lower in Group 5, as compared to Groups 2 and 3 (p < 0.05). The MDA levels in Group 1 and Group 5 were significantly lower than those in Group 3 (p < 0.05). CAT and GSH-Px activity was higher in Group 5 than in Group 2 and Group 3 (p = 0.00). Tissue damage scores were elevated in all the groups compared with sham group, but the treatment with the different doses of Dxp before reperfusion ameliorated the tissue damage scores., Conclusion: The results showed that Dxp reduced ovarian I/R injury.

Objective: Dexpanthenol (Dxp), antioxidant and anti-inflammatory agent, plays an important role in the repair systems against oxidative stress and inflammatory response. The objective of this study is to determine the effect of Dxp on experimental endometriosis model., Study Design: A prospective experimental study was conducted in Experimental Animal Laboratory of Mustafa Kemal University, Hatay. Twenty nonpregnant female Wistar albino rats, in which experimental model of endometriosis was surgically induced, were randomly divided into 2 groups. Group 1 was administered 500 mg/kg/d Dxp intraperitoneally for 14 days, and group 2 was given the same amount of saline solution. After 2 weeks of medication, the rats were killed and implant volumes, histopathologic scores; and levels of serum total antioxidant status, total oxidant status (TOS), and oxidative stress index (OSI) were evaluated. Plasma and peritoneal fluid levels of tumor necrosis factor α (TNF-α) were analyzed., Results: The endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values were significantly decreased ( P < .05) in the Dxp group compared to the control group. Plasma and peritoneal fluid TNF-α levels were significantly decreased ( P < .05) in the Dxp group compared to the control group., Conclusion: Dexpanthenol has free radical scavenger effects, and antioxidant properties has significantly regressed endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values. Serum and peritoneal fluid TNF-α levels were significantly decreased in the Dxp group. So Dxp decreased oxidative stress.

Aim: To assess short-term efficiency of hopantenic acid (pantogam) in the treatment of children with hyperkinetic behavior disorder, in whom the previous treatment with atomoxetine was not efficient., Material and Methods: Twenty-four children (16 boys and 8 girls), aged 6-11 years, diagnosed with hyperkinetic behavior disorder (ICD-10 item F90.1) were enrolled in this open non-randomized study., Results and Conclusion: A short-term positive therapeutic dynamics was observed when introducing hopantenic acid (pantogam) augmentation strategy to existing atomoxetine therapy. Qualitative improvements in children's state were found not only in the ability to control symptoms but also in their social functioning levels and quality of life. The proposed therapeutic strategy can help to improve treatment outcomes for children with certain clinical forms of hyperkinetic behavior disorder.

Clinical studies and experience in the use of pantogam (hopanthenic acid) and pantogam active (rac-gopantenic/D-, L-gopantenic acid) showed their efficacy and safety in patients with various pathologies. Pantogam has a unique spectrum of pharmacological effects (nootropic, anticonvulsant, mild activating) in the absence of addiction, hyperstimulation or withdrawal syndrome. Pantogam active, having also an additional anxiolytic effect, is characterized by bimodal activity, improves not only cognitive functions, but also emotional state in patients in psychiatric, neurological and cardiological practice with such diseases and conditions as anxiety/anxiety-depressive disorders, chronic brain ischemia, ischemic heart disease, chronic heart failure, arterial hypertension, epilepsy, craniocerebral trauma, schizophrenia as well as cognitive impairment in the structure of neurological and psychogenic deficiencies.

Aim: To assess the efficacy and safety of pantogam active (PA) in prevention and correction of neurological side-effects during the course neuroleptic treatment of acute endogenous psychoses., Material and Methods: Eighty schizophrenic patients (mean age 33 years) with acute psychosis were examined. All patients received 28-day course treatment with typical and atypical neuroleptics. Two equal groups were studied: patients of the first group were treated with trihexyphenidyl (THP) in dose of 0,002-0,012 mg and patients of the second group received in addition PA in dose 0,9 mg/day. Clinical-observation, psychometric scales (PANSS, CGI-S, UKU) were administered at baseline and in 1st,3rd,7th, 14th, 21st, 28st day., Results: PA in the combination with THP improved tolerability to neuroleptic therapy in whole and exerted the better correction effect on neuroleptic extrapyramidal disorders (EPD) compared to THP monotherapy. The number of patients with ERD was reduced by 1.5 times and prevention of EPD was observed 3 times more frequent in the group treated with PA. In the THP group, other adverse effects (AE) were 1,7 times more frequent and the total AE score was 2,5 times greater compared to the PA group (131 vs 50). Correction and preventive effects of the combined treatment on the clinically severe symptoms of EPD (akathisia, muscle dystonia) were more frequent in patients treated with typical neuroleptics. A less amount of THP (by 1,2 times) was used to stop EPD in the PA group., Conclusion: PA in the combination with THP has demonstrated the clear neuroprotective effect on the development, frequency and clinical presentations of neurological side-effects. The РА can be recommended as a drug of choice for correction and prevention of neuroleptic side-effects, it promotes their tolerability and improves quality of life during the course treatment.

Aim: To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups., Material and Methods: One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention., Results and Conclusion: There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

Various creams are available for superficial second-degree burns (SSDB) of the face. We evaluated provitamin pantothenic acid versus β-glucan for SSDB of the face using the O2C laser Doppler system and digital photo analysis. Out of 20 patients (January to December 2012) with facial burns, 7 with SSDB of both cheeks were included to our study. Burned cheek wounds were treated using pantothenic acid or β-glucan. Digital photos of marked regions were taken daily from predefined distances. Microcirculation was measured at marked regions for 7 days at scheduled time points using the O2C laser Doppler. Data were evaluated using the SPSS program (SPSS Inc., Chicago, IL). Wounds treated with β-glucan showed faster reepithelialization. O2C laser Doppler measurements showed faster increase in SO2, microvascular perfusion, hemoglobin content, and blood flow. This correlated good with clinical Vancouver Scar Scale results. Although not statistically significant, β-glucan cream therapy of SSDB results in aesthetically superior outcome and faster reepithelialization., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Acne vulgaris is a disease of the sebaceous follicle which affects up to 90% of adolescent patients. Topical retinoids, benzoyl peroxide and antibiotics are the main treatments for mild to moderate acne vulgaris. The use of such topical treatments is often associated with local irritation and dryness making the skin more sensitive to the sun. The aim of our study was to assess the efficacy and skin tolerability of a fixed-dose combination therapy with hydrogen peroxide (4%), Salicylic acid (0.5%) and D-panthenol (4%) (HSD) gel, in mild-moderate acne vulgaris, during the period of sun exposure., Patients and Methods: We retrospectively observed 30 patients of Central Italy with mild to moderate acne between April and September 2012. All the patients selected underwent only therapy with HSD gel once a day in the evening for 60 days, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale., Results: The mean GES value showed a statistically significant reduction: 2.03 (SD 0.81) at baseline, 1.63 (SD 0.81) and 0.90 (SD 0.71) respectively at 30 and 60 days (p < 0.01). 21 (70%) and 27 patients (90%) did show good or very good tolerability at 30 and 60 days respectively., Conclusions: Topical treatments with retinoids, antibiotics and antiseptics may increase skin irritation reducing patient adherence to the treatment. HSD gel has shown a good skin tolerability and efficacy in reducing acne lesions, even during the sun exposure period in which traditional treatments should be cautiously used.

Background: Vitiligo is an acquired idiopathic cutaneous disease characterized by pearly white patches of variable shapes and sizes. Various medical and surgical therapeutic options have been proposed to achieve repigmentation; phototherapy is one of the most efficient options. Topical therapies have been a mainstay of vitiligo treatment, with or without phototherapy., Aim of the Work: To compare the efficacy of combined topical antioxidant hydrogel and excimer light versus excimer light alone in treating vitiligo., Patients and Methods: Thirty patients were included in this comparative, prospective, randomized study. For each patient, at least 2-4 vitiliginous macules were randomly selected and treated while an untreated vitiliginous macule served as control. Lesions were divided into two groups: Group A received combination therapy of daily topical antioxidant plus excimer light, while Group B received only excimer light. Lesions were treated twice a week for a maximum of 24 sessions. Initial fluencies were adjusted individually according to the minimal erythema dose in vitiliginous skin. Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians., Results: Group A lesions showed significant efficacy than group B (p < 0.001), specially on treating UV-sensitive lesions with no side effects., Conclusion: Topical antioxidant and excimer light represents a valuable, effective therapy for localized vitiligo.

A clinical case of a child with hyperkinetic conduct disorder is presented, with symptoms of hyperkinetic disorder itself closely intertwining with symptoms of conduct disorder. The qualitative changes in the child's condition are noted, including not only achieved control over the symptoms, but also improved social functioning level, achieved by means of Pantogam (neuroprotective drug) addition to atomoxetine therapy. The proposed strategy can contribute to improvement of treatment results for children with certain clinical types of hyperkinetic conduct disorder.

Aim: To evaluate the efficacy and tolerability of rac-hopantenic acid (pantogam activ) in patients with mixed anxiety-depressive disorder and anxiety-depressive disorder with chronic cerebral ischemia., Material and Methods: A total of 50 patients were examined (30 patients in the main group, 20 patients in the control one). All patients received standard therapy with SSRI antidepressants. Rac-hopantenic acid at a daily dose of 1200 mg was included in the complex therapy of patients of the main group. Duration of the therapy with rac-hopantenic acid was 21 days. Psychopathological, psychometric and detailed somatic examinations were performed., Results: In the main group, the combination of pantogam activ and antidepressants promoted distinct balanced nootropic, antidepressant and anxiolytic effects, as well as the improvement of health outcomes. The reduced total number of adverse events (less frequent drowsiness and headaches) was noted as well., Conclusion: The rapid and reliable reduction of anxiety, depression and cognitive impairment during concomitant therapy with antidepressants and pantogam activ was identified.

Objective: Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD., Methods: Forty rat pups were divided into four groups: control, control + Dxp, hyperoxia and hyperoxia + Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates., Results: Lung injury score and alveol diameter increased in the hyperoxia group (p < 0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control + Dxp and hyperoxia + Dxp groups (p < 0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia + Dxp group had lower tumor necrosis factor-α and interleukin-1β median levels compared to the hyperoxia group (p = 0.007)., Conclusion: Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD.

Background: Problems affecting the vaginal tract in diabetic women are very often neglected. The efficacy and safety of three gynecological treatments in diabetic women have been assessed., Materials and Methods: A single-blind randomized progressive trial on 48 diabetic women affected by vaginal dryness, dyspareunia, and recurrent Candida infections was carried out. The ICIQ Vaginal Symptoms (ICIQ-VS) questionnaire was administered., Results: The analysis of the parameters of ICIQ-VS questionnaire among the three groups showed significant difference only for "dragging pain" (p = 0.0 19) and "soreness" (p = 0.028). In all groups and for all parameters of the questionnaire, improvement of symptoms was observed. In particular, in Group 1 for all symptoms a highly significant difference was observed, to support the already known benefits of the products and of the proposed combination. Significant improvement was also observed in Group 2., Conclusions: The proposed treatment with DermoXEN® Ultracalming Special for diabetics and DermoXEN® Vitexyl vaginal gel exert effective moisturizing and soothing action. Indeed, the aforementioned products have been proven effective for the main gynecological problems of diabetic women.

Background/purpose: In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC., Methods: Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically., Results: Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively)., Conclusions: Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: A number of synthetic pantothenate derivatives, such as pantothenamides, are known to inhibit the growth of the human malaria parasite Plasmodium falciparum, by interfering with the parasite Coenzyme A (CoA) biosynthetic pathway. The clinical use of pantothenamides is limited by their sensitivity to breakdown by ubiquitous human pantetheinases of the vanin family., Methods: A number of pantothenate derivatives (pantothenones) with potent and specific inhibitory activity against mammalian vanins were tested in a proliferation assay of asexual P. falciparum blood stages alone, and in combination with pantothenamides., Results: The vanin inhibitors were found to protect pantothenamides against breakdown by plasma vanins, thereby preserving the in vitro anti-malarial activity. Moreover, some of the vanin inhibitors showed in vitro anti-malarial activity in the low micromolar range. The most potent antimalarial in this series of compounds (RR8), was found to compete with pantothenate in a combination proliferation assay. No correlation, however, was found between anti-vanin and anti-malarial activity, nor was pantetheinase activity detected in P. falciparum extracts., Conclusions: Growth inhibition is most likely due to competition with pantothenate, rather than pantetheinase inhibition. As vanin inhibitors of the pantothenone class are stable in biological fluids and are non-toxic to mammalian cells, they may represent novel pantothenate-based anti-malarials, either on their own or in combination with pantothenamides.

The article summarizes clinical features of the course when chronic pancreatitis goes in combination with diseases of gastroduodenal and hepatobiliary systems and features of functional and morphological changes. The article also represents justification of need to include the combined medicine Doktovit (combination of Dexpanthenol and S-methylmethionine) into complex treatment of the pathology, describes mechanism of its gastro protective and reparative action.

Objective: To study cognitive impairment and the efficacy of hopantenic acid (pantogam) in children, aged from 4 to 7 years, with epilepsy and cognitive impairment., Material and Methods: The study included 40 children with epilepsy treated with pantogam (the main group) and 23 children with epilepsy who did not receive pantogam (the comparison group). All children were diagnosed with cryptogenic epilepsy and symptomatic epilepsy. We presented the main results of the clinical examination including routine EEG, video-EEG monitoring and brain MRI. An analysis of cognitive impairment in children of the comparison group and in the main group before and after treatment with pantogam was performed using a set of neurocognitive tests (the Luscher Color Test, «Piano playing test», «Three word test» and «Four is redundant test»)., Results and Conclusion: There were a significant decrease in cognitive impairment in children of the main group compared to the comparison group as well as age normalization and improvement of EEG after 2 months of treatment in 15% of the patients. The good tolerability of the drug and no increase in the frequency of seizures were observed.