Zinc in dermatology.

Zinc has numerous pharmacological uses in dermatology. Its antioxidant and immunomodulatory properties are thought to correlate with its efficacy in acne vulgaris and leishmaniasis, amongst other cutaneous conditions. We conducted a review of the literature on the use of zinc in dermatology; in particular, we investigated its role in acne vulgaris, hair loss, hidradenitis suppurativa, leishmaniasis, and warts. We searched MEDLINE selecting only articles in English and evaluating the evidence using the Oxford Center of Evidence-Based Medicine 2011 guidance. This review has found evidence to support the use of zinc in patients in infectious conditions (leishmaniasis and warts), inflammatory conditions (acne rosacea, hidradenitis suppurativa) and in hair loss disorders.Ppatients with zinc deficiency should also receive oral supplementation. Further research and large randomized controlled trials are required to investigate the role of zinc as a monotherapy.

Fabrication and Evaluation of Celecoxib Oral Oleogel to Reduce the Inflammation of Ulcerative Colitis.

Oleogel consists of hydrophobic solvent and an oleogelator. In this study, attempts were made to study the influence of Celecoxib solubility, concentration and dispersability on its release, absorption, and biological performance. Oleogels were prepared to study the formulation variables on its stability and release. Castor oil was selected as the oil and the oleogelator concentration was 4.5% w/w. F3 revealed the highest release and stability compared to other formulae. The percent permeated across the rat intestine showed a 7.5-fold increase over free Celecoxib, and its lifetime was found to be greater than 18 months. The efficacy of free Celecoxib and oleogel formulae to treat rats with ulcerative colitis was done via the induction of ulcerative colitis (UC) through administration of 5% dextran sodium sulphate (DSS). Celecoxib besides its formulae significantly reduced the release of Leucine rich 2 glycoprotein (LRG), Myeloperoxidase (MPO), Tumor necrosis factor-α (TNF-α), proinflammatory cytokine expression, High mobility group box 1 (HMGB1), Nuclear factor kappa B (NF-ΚB), Trefoil Factor 3 (TFF3), Metalloproteinase-3 (MMP3), and miRNA31. Moreover, F3 significantly increased the colonic cAMP in DSS treated rats and reduced the intestinal inflammation beside healing of mucosa and restitution of the epithelium of the gastrointestinal tract.

Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds.

BACKGROUND: Regardless of the enormous success of vaccines over decades, the formulation of biocompatible and highly effective vaccines is still insufficient for combating new pathogens. DISCUSSION: The degree of effectiveness of any vaccine largely depends on the choice of appropriate adjuvant. Along with the optimum biocompatibility, an ideal adjuvant must be biodegradable, economical and easy to manufacture. To date, various organic and inorganic substances have been used as an adjuvant to augment the effectiveness of the vaccine. Immunological adjuvants are essential for strong and long-term effects against various pathogens. However, a very limited number of licensed adjuvants are available for the formulation of a successful vaccine. This leads to a challenging situation in medical science. CONCLUSION: The present review concisely summarizes the mechanism of action of various bioactive organic and inorganic immunological adjuvants, their limitations and future perspectives for their appropriate modification. Current trends of anticancer therapies using immunological adjuvants have also been highlighted in this review.

Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial.

BACKGROUND: The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC, ) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome. METHODS: This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded. DISCUSSION: The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018).

Immunotropic Properties of an Experimental Synthetic Selenium-Organic Compound.

We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.

Oleogel-S10 Phase 3 study "EASE" for epidermolysis bullosa: study design and rationale.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare, genetic diseases that affect the integrity of epithelial tissues, most notably the skin. Patients experience recurrent skin wounding, with severity depending on type, sub-type, and mutation. Oleogel-S10, a formulation of birch bark extract, has demonstrated efficacy in a Phase 2 trial assessing re-epithelialization of wounds in EB. EASE (NCT03068780, EudraCT 2016-002066-32) is a randomized, Phase 3, placebo-controlled study designed to determine the efficacy of Oleogel-S10 versus placebo in patients with EB. METHODS: EASE is a Phase 3, two-phase study comprising a 90-day, double-blind, randomized, placebo-controlled phase, followed by 24 months of open-label, single-arm follow-up. Patients with junctional EB, dystrophic EB, or Kindler syndrome and target wounds (10 - 50cm2) present for > 21 days and < 9 months, are randomized in a 1:1 ratio to receive wound dressings according to local standard of care with or without Oleogel-S10. Placebo is based on the Oleogel-S10 vehicle, which is sunflower oil formulated to have a consistency indistinguishable from that of the active product. The primary endpoint of the trial, directed by the US health authority according to the required study endpoints for chronic cutaneous ulcer and burn wounds, is to compare the efficacy of Oleogel-S10 versus placebo according to the proportion of patients with complete closure of the target wound within 45 ± 7 days of treatment. Additional EB-focused endpoints include wound burden, patient-reported outcomes, and safety. RESULTS: Results of the primary endpoint are anticipated to be available by H2 2019. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03068780 . EudraCT, 2016-002066-32. Registered on 3 March 2017.

OLEOGEL-S10 TO ACCELERATE HEALING OF DONOR SITES: MONOCENTRIC RESULTS OF PHASE III CLINICAL TRIAL.

MATERIAL AND METHODS: Oleogel-S10, an ointment containing betulin-rich triterpene dry extract from birch bark was tested in an open, blindly evaluated, prospective, controlled, randomized multicentre study to improve wound healing in donor sites. The primary endpoint was time to wound closure, and secondary endpoints were scar related measurements at the time of wound closure, and 3 and 12 months after wound closure (POSAS, laser speckle contrast analysis, viscoelastic analysis). RESULTS: We report the results from a single centre (Department of Burns and Reconstructive Surgery, University Hospital Brno) of this phase III clinical trial. A total of 32 patients (25 men and 7 women) were included with the mean patient age of 41.8 years (SD, ±11.66). The mean extent of patients donor sites in the study was 56.77cm2 (SD, ±20.39). Median healing time of the verum group (Oleogel-S10) was 7 days (95% Confidence Interval 7-8 days) and for controls 8 days (95% CI 7-10 days). Comparison of POSAS data from the verum group revealed significantly lower values at all three time points as compared to the controls. Perfusion of scars of the verum group reached on average of 115 perfusion units at the end of treatment; the average was 69.8 perfusion units at the 3-month follow-up and 50.2 perfusion units at the 12-month follow-up. Control sites displayed significantly higher values at all time points (122.2 perfusion units, 73.9 perfusion units, 52.2 perfusion units). Significant differences were detected in the skins viscoelastic properties, with sites treated with Oleogel-S10 displaying more favourable values. CONCLUSION: In our results, we demonstrate the significant effectiveness of Oleogel-S10 in donor sites healingKeywords: Donor site, Triterpenes, Oleogel-S10, wound closure.

Organic Dye Based Nanoparticles for Cancer Phototheranostics.

Phototheranostics, which simultaneously combines photodynamic and/or photothermal therapy with deep-tissue diagnostic imaging, is a promising strategy for the diagnosis and treatment of cancers. Organic dyes with the merits of strong near-infrared absorbance, high photo-to-radical and/or photothermal conversion efficiency, great biocompatibility, ready chemical structure fine-tuning capability, and easy metabolism, have been demonstrated as attractive candidates for clinical phototheranostics. These organic dyes can be further designed and fabricated into nanoparticles (NPs) using various strategies. Compared to free molecules, these NPs can be equipped with multiple synergistic functions and show longer lifetime in blood circulation and passive tumor-targeting property via the enhanced permeability and retention effect. In this article, the recent progress of organic dye-based NPs for cancer phototheranostic applications is summarized, which extends the anticancer arsenal and holds promise for clinical uses in the near future.

[MODERN APPROACHES TO CORRECTION OF HYPERNATREMIA IN NEUROSURGICAL PATIENTS].

The article presents the analysis of the intensive therapy through the correction of persistent hypernatremia in neurosurgical patients after removal of brain tumors. The aim of this work was to evaluate the effectiveness of Sterofundin in the framework of complex therapy of hypernatremia in neurosurgical patients after removal of brain tumors. We analyzed the dynamics of the concentrations of sodium, potassium, chorus of the plasma, anion gap and buffer bases in the postoperative period of these patients. For obtaining reliable results, the patients were divided into groups according to the nature of the treatment: Sterofundin and symptomatic correction of hypotonic solution of sodium chloride, saluretic and Verospiron respectively. In a comparison between the groups, a distinct difference in the speed of regression of hypernatremia and durability of the achieved effect was observed. In case of treatment with Sterofundin there was a significant decrease of hypernatremia by the end of the second day of the postoperative period without tendency to re-raise. The prevalence of hypotonic solutions of sodium chloride and potassium-sparing saluretics in intensive care allowed reducing the sodium concentration non-persistently to the fourth day on the background of significant fluctuations in its concentration. The use of Sterofundin in complex therapy of electrolyte disturbances, particularly of hypernatremia in neurosurgical patients after removal of brain tumors, is reflected in the form of significant regression of increased sodium concentration in plasma compared with the method of use "hypotonic" hemodilution, saluretics and potassium-sparing diuretics.

Weight training and appropriate nutrient supplementation as an alternative method to pharmacological treatment in rehabilitation of post-myocardial infarction patients.

The article describes the impact of weight training, micro-elements and vitamins on rehabilitation in post-myocardial infarction patients. Cardiac rehabilitation is a multi-disciplinary and multi-faceted intervention aimed at restoring well-being and retarding disease progression in patients with heart disease. It has been shown that exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality. Intake of vitamins and other diet supplements was reported to exert beneficial effects. Pharmacological medication is associated with an increased risk of severe arrhythmia, and many adverse outcomes. Therefore, since conventional medicine only relieves the symptoms, cellular nutrition should be used in order to improve the quality of life in post-myocardial infarction patients. These elements prevent another infarction. The following nutrients are reported to have beneficial effects on general and cardiovascular health: amino acids, vitamins, coenzyme Q10, pycnogenol, inositol, omega-3 fatty acids, macromineral elements, and trace mineral elements. In conclusion, the review indicates that appropriate weight training and diet supplementation ensure full recovery and elimination of risk factors for cardiovascular diseases.

Organic stealth nanoparticles for highly effective in vivo near-infrared photothermal therapy of cancer.

In recent years, a wide range of near-infrared (NIR) light absorbing nanomaterials, mostly inorganic ones, have been developed for photothermal therapy (PTT) of cancer. In this work, we develop a novel organic PTT agent based on poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), a conductive polymer mixture with strong NIR absorbance, for in vivo photothermal treatment of cancer. After being layer-by-layer coated with charged polymers and then conjugated with branched polyethylene glycol (PEG), the obtained PEDOT:PSS-PEG nanoparticles are highly stable in the physiological environment and exhibit a stealth-like behavior after intravenous injection with a long blood circulation half-life. As a result, an extremely high in vivo tumor uptake of PEDOT:PSS-PEG attributed to the tumor-enhanced permeability and retention effect is observed. We further use PEDOT:PSS-PEG as a PTT agent for in vivo cancer treatment and realize excellent therapeutic efficacy in a mouse tumor model under NIR light irradiation at a low laser power density. Comprehensive blood tests and careful histological examination reveal no apparent toxicity of PEDOT:PSS-PEG to mice at our treated dose within 40 days. To our best knowledge, this work is the first to use systemically administrated conductive polymer nanoparticles for highly effective in vivo PTT treatment in animals and encourages further explorations of those organic nanomaterials for cancer theranostic applications.

Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF.

This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)(-1)) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced by [corrected] 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.

Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF-κB.

Ulcerative colitis and Crohn's disease are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract. Nuclear Factor Kappa B (NF-κB) is a transcription factor that plays a key role in regulating expression of multiple inflammatory and immune genes. In this study, a Topological Virtual Screening study has been carried out to achieve a model capable of finding new compounds active in ulcerative colitis by inhibiting NF-κB. Different topological indices were used as structural descriptors, and their relation to biological activity was determined using linear discriminant analysis. A topological model consisting of two discriminant functions was built up. The first function focused in the discrimination between NF-κB active and inactive compounds, and the second one in distinguishing between compounds active and inactive on ulcerative colitis. The model was then applied sequentially to a large database of compounds with unknown activity. Twenty-eight of such compounds were predicted to be active and selected for in vitro and in vivo testing.

Diphoterine for alkali chemical splashes to the skin at alumina refineries.

BACKGROUND: Diphoterine is a commercially available amphoteric, hypertonic, chelating solution used to decontaminate and irrigate chemical splashes. The aim of this study was to evaluate the implementation of Diphoterine at three alumina refineries. This is the largest case series reported to date. METHODS: One hundred eighty cases of alkali splashes to the skin were evaluated clinically. Two groups were compared; those who had applied Diphoterine first and those who had applied water first. RESULTS: There were no signs of chemical burn in 52.9% of the group who applied Diphoterine first compared with 21.4% of the group who applied water first. Only 7.9% of the group who applied Diphoterine first had blisters or more severe signs compared with 23.8% of the group who applied water first. The differences were statistically significant (P < 0.001). After implementation of Diphoterine the "first aid" injury rate for chemical burns fell 24.7% (95% CI 0.5­43.0%). CONCLUSIONS: Applying Diphoterine first was associated with significantly better outcomes following alkali skin splashes than applying water first.

Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking.

OBJECTIVES: A significant minority of the population consume multi-vitamins/minerals for their putative health benefits, including potentially beneficial effects on cognitive performance, fatigue and mood. The current study investigated the effect of supplementation with a multi-vitamin/mineral on fatigue and cognitive function in healthy females. METHODS: In this placebo-controlled, double blind, randomized, parallel groups trial the effect of a multi-vitamin/mineral (Supradyn) was assessed in 216 females aged 25-50 years. Participants attended the laboratory before and 9 weeks after commencing treatment. During both visits cognitive function and the modulation of task related mood/fatigue were assessed in two discrete 20-min assessment periods during which participants completed a four-module version of the Multi-Tasking Framework. RESULTS: Those in the vitamin/mineral group exhibited an attenuation of the negative effects of extended task completion on mood/fatigue. Multi-tasking performance for this group was also improved in terms of accuracy across all tasks, and on two of the individual tasks (Mathematical Processing and Stroop) in terms of both faster and more accurate responses. Analysis of a subsection (N = 102) demonstrated significant reductions in homocysteine levels following the vitamins/mineral supplement. CONCLUSIONS: These findings suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation.

Decontamination of tetramethylammonium hydroxide (TMAH) splashes: promising results with Diphoterine in vitro.

Tetramethylammonium hydroxide (TMAH), used in microelectronic industries and research and development, has both corrosive properties and systemic toxicity. Two fatal TMAH occupational exposure cases have been published. Studies comparing initial TMAH decontamination with Diphoterine versus tap water were performed: an in vitro pH titration study and an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) in vitro cytotoxicity cell viability assay. For pH normalization, 17 times more tap water than Diphoterine was required. In the cytotoxicity test, two-thirds of the cells remained viable after Diphoterine washing, compared with only one-third after tap water washing (p < .001). Diphoterine washing is a promising TMAH decontamination method.

Antibiotic batumin for diagnostics of staphylococci and treatment of Staphylococcus aureus nasal carriage.

Paper disks containing 5 microg of antibiotic batumin (preparation "Diastaph") were tested using standard disk diffusion technique against 1520 strains of bacteria (clinical isolates of different genera and type strains of staphylococci and micrococci). Presence of growth inhibition zone 17 mm and more around the disk gave evidence that the isolate belonged to the genus Staphylococcus. Method ensured quick and reliable identification of all strains of this genus. Batumin 0,1% ointment was used for treatment of nasal carriage of Staphylococcus aureus by medical staff (56 persons) in the Institute of Traumatology and Orthopedics, 5th maternity house and the Ukrainian Septic center (Kyiv) where the nasal carriage of S. aureus was diagnosed in 22, 21, and 11% of staff accordingly. It was applied locally to the anterior nares twice a day for 5-7 days. The complete eradication of S. aureus was 83,6% with batumin ointment, 73,3% and 69,4% with preparation of comparison baneacin and bactroban. Thus the proposed combination of batumin-containing disks and ointment provided reliable and quick identification of staphylococci and has shown its high effectiveness in the control of the nasal carriage of Staphylococcus hospital strains.

Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro.

Raltegravir (MK-0518) is a potent inhibitor of human immunodeficiency virus (HIV) integrase and is clinically effective against viruses resistant to other classes of antiretroviral agents. However, it can select mutations in the HIV integrase gene. Nine heavily pretreated patients who received salvage therapy including raltegravir and who subsequently developed virological failure under raltegravir therapy were studied. For each patient, the sequences of the integrase-coding region were determined and compared to that at the beginning of the treatment. Four different mutation profiles were identified in these nine patients: E92Q, G140S Q148H, N155H, and E157Q mutations. For four patients, each harboring a different profile, the wild-type and mutated integrases were produced, purified, and assayed in vitro. All the mutations identified altered the activities of integrase protein: both 3' processing and strand transfer activities were moderately affected in the E92Q mutant; strand transfer was markedly impaired in the N155H mutant; both activities were strongly impaired in the G140S Q148H mutant; and the E157Q mutant was almost completely inactive. The sensitivities of wild-type and mutant integrases to raltegravir were compared. The E92Q and G140S Q148H profiles were each associated with a 7- to 8-fold decrease in sensitivity, and the N155H mutant was more than 14-fold less sensitive to raltegravir. At least four genetic profiles (E92Q, G140S Q148H, N155H, and E157Q) can be associated with in vivo treatment failure and resistance to raltegravir. These mutations led to strong impairment of enzymes in vitro in the absence of raltegravir: strand transfer activity was affected, and in some cases 3' processing was also impaired.