[Clinical and neurophysiological manifestations of sluggish cognitive tempo in children]. / Kliniko-neirofiziologicheskie proyavleniya nizkogo kognitivnogo tempa u detei.

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 «SCT¼ (Sluggish Cognitive Tempo) for assessing manifestations of low cognitive tempo, the «RAM¼ 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.

Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis.

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.

[Use of dexpanthenol in corneal damage]. / Primenenie dekspantenola pri povrezhdenii rogovitsy.

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.

Efficacy of intramuscular injections of biotin and dexpanthenol in the treatment of diffuse hair loss: A randomized, double-blind controlled study comparing two brands.

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.

Non-clinical safety profile and pharmacodynamics of two formulations of the anti-sepsis drug candidate Rejuveinix (RJX).

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.

The Effectiveness of Galactomyces Ferment Filtrate, Dexpanthenol, and Centella Asiatica Combination Serum in the Treatment of Post-Acne Hyperpigmentation in Subjects with Skin of Color.

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.

Exploring Heteroaromatic Rings as a Replacement for the Labile Amide of Antiplasmodial Pantothenamides.

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.

Molecular effects of photon irradiation and subsequent aftercare treatment with dexpanthenol-containing ointment or liquid in 3D models of human skin and non-keratinized oral mucosa.

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.

Cyclic Phosphopantothenic Acid Prodrugs for Treatment of Pantothenate Kinase-Associated Neurodegeneration.

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.

Randomised trial on performance, safety and clinical benefit of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms.

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).

[Pharmacotherapy of psychomotor developmental delay in 6-12 months preterm infants with hypoxic-ischemic encephalopathy (the double-blind comparative multicenter placebo-controlled study)]. / Farmakoterapiia zaderzhki psikhomotornogo razvitiia u detei 6-12 mes, rozhdennykh nedonoshennymi i perenesshikh gipoksicheski-ishemicheskoe porazhenie golovnogo mozga (dvoinoe slepoe sravnitel'noe mnogotsentrovoe platsebo-kontroliruemoe issledovanie).

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.

Is it possible to prevent contrast-induced nephropathy with dexpanthenol?

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.

The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration.

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.

Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation.

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.

Evaluating the Effects of a Topical Preparation with Dexpanthenol, Silbiol, Undecylenic Acid, and Lidocaine on Palatal Mucosa Wound Healing in a Rat Model

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) mm2 in the control group and 5.07 (0.88) to 1.42 (1.67) mm2 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.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Liver Injury.

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.

[Possible applications of rac-hopantenic acid in the treatment of cognitive, anxiety and depressive disorders in patients with essential arterial hypertension]. / Vozmozhnosti D-, L-gopantenovoi kisloty v lechenii kognitivnykh i trevozhnykh rasstroistv u bol'nykh s éssentsial'noi arterial'noi gipertenziei.

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.

HISTOLOGICAL EVALUATION OF THERAPEUTIC EFFECTS OF DEXPANTHENOL COMPOSITION WITH CERAMIDES IN RATS WITH SKIN BURN INJURY.

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 «Bepanten¼ 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.

Quantitative and Qualitative Pathogenetic Indices for Review of Data Derived from Homeopathic Pathogenetic Trials.

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.

Use of Vitamins and Dietary Supplements by Patients With Multiple Sclerosis: A Review.

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.