Neutral Cream Research Articles

Healing Activity of Propolis of Stingless Bee (Scaptotrigona aff. postica), Reared in Monoculture of Açaí (Euterpe oleracea), in Induced Wounds in Rats.

Wound healing is a complex and coordinated process involving interactions between cells and various messenger systems. This study conducted in vivo tests to determine the healing effect of propolis (PR)-based cream derived from the Amazon stingless bee, Scaptotrigona aff. postica, reared in açaí (Euterpe oleracea) monoculture, on induced wounds in rats. Data were obtained by monitoring injuries on 14 Wistar rats, divided into three groups (G1, G2 and G3), each receiving specific treatments: propolis-based cream (PR), collagenase (PC) and neutral cream (NC). Over the seven days of treatment, the lesions were measured using photographic records and ImageJ software to evaluate the healing effectiveness of the test cream. ImageJ software version 1.53g was used to compare the wound diameters for each treatment. After seven days, histopathological analyses of the induced lesions were performed. It was observed that collagenase (PC) and the test cream (PR) did not differ significantly in terms of wound diameter reduction. However, the propolis-based cream directly influenced the lesion maturation process and exhibited a milder inflammatory response compared to the positive control (PC). This effect is possibly associated with antimicrobial and anti-inflammatory compounds identified by GC/MS analysis in the propolis. Notably, this is the first report describing propolis of Scaptotrigona aff. postica obtained from açaí monocultures with strong healing potential, highlighting the identification of a high concentration of phenolic compounds that aid directly in wound repair.

Do We Have a New Psoriasis Drug?

Pentadekapeptide BPC 157 was used in numerous laboratory rat animal models with proven cytoprotective and organ protective properties. In different wound therapy (incisional/excisional wound, deep burns, diabetic ulcer, alkali burns) fast and complete tissue restitution was achieved. BPC 157 was found to rapidly stimulate the expression of various genes involved in the healing process of the skin and mucosal lesions in these models. Psoriasis is a chronic, relapsing, immune‐mediated skin disease pathogenically driven by proinflammatory cytokines of which: TNF‐alpha, IL‐12, IL‐17, IL‐23 play a key role. Since BPC 157 has shown a significant anti‐inflammatory effect in several studies, the aim of this study is to show that it has the same role in the regression of inflammatory skin lesions such as those in psoriasis. An experimental model of psoriasis in laboratory animals is easily feasible, using 5% imiquimod topically.MATERIALS AND METHODS The experiment is done on male Wistar Albino rats. Animals are divided into groups of 6. „Psoriasis‐like” lesions are induced in all animals applying 5% imiquimod cream topically on shaved skin on their backs for 7 consecutive days. On the 7th day, 3 hours after applying imiquimod cream treatment starts usage BPC 157 in cream (conc. 1μg/g neutral cream) or only neutral cream (Belobaza) in control groups. Animals are treated and observed daily, video documentation was made. Animals are treated until the sacrifice day according to schedule. The severity of skin lesions is measured clinically using a modified version of Psoriasis Area Severity Index‐PASI score. Modified PASI includes scoring the following lesion features: erythema, infiltration, desquamation on scale 1‐4; maximum modified PASI value is 12. Two way ANOVA and Bonferroni post hoc test were used for statistical analysis. Data represented as mean SD for N=6/group.RESULTS Animals treated using BPC 157 conc.1μg/g in a cream had significantly lower values of PASI score when compared to control group. Faster resolution of imiquimod induced „psoriasis‐like” lesions was achieved using BPC 157 when compared to control group.CONCLUSION BPC 157 is well‐known peptide used in various experimental models without any side effects of it's use, with proven effects on the NO‐system, and excellent results in wound healing. Psoriasis is a rather common immune‐mediated skin disease driven by proinflammatory cytokines. TNF‐alpha, IL‐12, IL‐17, IL‐23 play a key role in the pathogenesis of psoriasis. It is undisputably that the use of BPC 157 topically successfully neutralizes the effects of imiquimod and induces regression of „psoriasis‐like“ lesions, the question that needs to be answered yet is whether BPC 157 has an impact on one of the above‐mentioned cytokines. It is yet to be explored which mechanism is the key to it´s beneficial effects in treating „psoriasis‐like“ lesions in experimental models.

Efficacy and Safety of a Hyaluronic Acid–Containing Cream in the Treatment of Chronic, Venous, or Mixed-Origin Leg Ulcers: A Prospective, Multicenter Randomized Controlled Trial

Topical applications of hyaluronic acid (HA)-containing formulations, based on the complex and vital role of HA in all stages of the wound-healing process, are routinely used with standard therapy to promote faster healing of chronic wounds. However, evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. This study compared the efficacy and safety of topical application of a hyaluronic acid cream vs a neutral comparator (identical cream without HA) in treating subjects with chronic leg ulcers of vascular origin. This was a prospective, multicenter double-blind randomized controlled trial. One hundred sixty-eight subjects with chronic leg ulcers of venous or mixed (venous and arterial) origin were randomized to receive either topical applications of 0.2% HA cream or neutral comparator cream for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed at 20 weeks or before and confirmed 3 weeks later). In both groups, topical treatment was associated with standard therapy (ulcer cleansing and optimized compression). The proportion of subjects with centrally assessed complete healing of the target ulcer that was confirmed 3 weeks later (primary efficacy endpoint) was substantially higher in the HA cream group (31.3%) than in the neutral cream group (14.8%; P =.009). Results in the full analysis, per protocol, and as assessed by the investigator were consistent with primary results. No significant difference in treatment effect was observed when subjects were stratified according to baseline ulcer size (≤20 cm2 or >20 cm2) regardless of topical treatment. Safety and tolerability were comparable between treatments. Treatment of subjects with chronic leg ulcers of venous or mixed origin with HA cream is safe, well tolerated, and results in a higher rate of healing than a neutral comparator cream.

Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery via Macrophage Proliferation and Direct Collagen Production.

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.

Towards on-site automatic detection of noxious events in dairy cows

Successful detection of pain in cows could circumscribe the therapeutic window for treatment before the cow's condition deteriorates further. While severe clinical cases that are characterized as painful have clear behavioral and physiological manifestations, mild pain may go unnoticed in cows due to their stoic nature. This work presents the first step in developing a warning system that will enable the identification of mild pain in dairy cows. In a set of three experiments, a topical application of 10 % capsaicin cream was used to elicit a noxious sensation. Experiment 1 was aimed at establishing capsaicin as a noxious model for bovines (n = 11). Each cow was treated with neutral cream on day one and the noxious cream on day two. Since the duration of capsaicin effects on bovine skin is unknown, Experiment 2 was designed to evaluate capsaicin's impact on bovines 30 min after application (n = 17). Physiological signs were collected in response to the capsaicin cream application and were compared to the application of the neutral cream. In Experiment 3 physiological signs and continuous behavioral data were recorded (n = 22, four cows participated in Experiment 1). Each cow was treated with neutral cream on day one and the noxious cream on days two and three, i.e., repeated exposure to the noxious stimulus. Heart and breathing rates were elevated soon after the noxious treatment but not for the neutral cream. Blood oxygen saturation was inconclusive. Changes in daily activity patterns consecutive to the noxious challenge included a decrease in rumination time and an increase in lying bouts. These results are in line with what would be expected for physiological and behavioral effects of pain in cows. Additional data are required to rule out habituation or sensitization to the procedure. The resulting database was then used to develop a machine-learning algorithm to detect noxious sensations by applying random forest classifiers trained with two different approaches. The learning herd approach, in which a specialist labels a set of observations and uses them to derive a classifier for new observations from the same herd, achieved 82 % ±9% accuracy. The unlearning herd approach, in which a single database is used to train a classifier that can be applied to members of other herds, resulted in an accuracy of 86 %±18 %. The data discussed in this study meet the requirements of an automatic on-site noxious detection system; real-time on-farm measurements, informative of negative high-arousal states.

A Controlled Study to Examine the Effect of Topical Sucralfate on Radiofrequency-induced Burn Wounds in Rats

This study aimed to evaluate the effect of 10% topical sucralfate on healing radiofrequency-induced burn wounds in rats. Twenty (20) male rats were divided into 2 equal groups. Using radiofrequency, 4 full-thickness, 1 cm in diameter round burns were created on the backs of the rats that then were randomized to receive twice-daily treatment for 30 days with 10% sucralfate or neutral cream. Biopsies were taken on days 4, 7, 14, and 21 to analyze fibrin-leukocyte crut, edema density, epidermal-dermal cell infiltration, amount of fibroblast and collagen fibers, amount of elastic fibers, neovascularization-angiogenesis, and reepithelialization-granulation tissue. Data were collected to a spreadsheet and entered into statistical software for analysis. Histopathological features were classified as categorical variables and compared using the χ2 test and Fisher's exact test. When χ2 was used, Yates' correction for continuity was performed. All reported P values were 2-tailed; P less than .05 was considered statistically significant. On day 4, improvement in edema density (P = .034), epidermal detachment (P = .020), epidermal-dermal cell infiltration (P = .007), and polymorphonuclear leukocyte infiltration (P = .021) were statistically more significant in the sucralfate than control group. On day 7, epidermal-dermal cell infiltration (P = .007) and elastic fibers P = .050) were statistically more significant in the sucralfate group. On day 14, angiogenesis (P = .029), reepithelialization (P = .035), and granulation tissue (P = .003) were statistically more significant in the sucralfate group. By the end of the study (day 30), angiogenesis (P = .010), reepithelialization (P <.001), fibroblast density (P = .016), granulation tissue (P = .035), and collagen density (P = .002) were significantly improved in the sucralfate group versus the control group. In a rat wound model, 10% topical sucralfate was found to histopathologically facilitate the healing process compared to the control group. Controlled clinical studies are needed to elucidate the effect of this treatment in human wounds.

Pure, stable and highly antioxidant lignin nanoparticles from elephant grass

Finding renewable and green resources for nanomaterial preparation is a compelling topic concerning the sustainability in nanotechnological applications. In particular, lignin-based nanoparticles are pivotal for unlocking the use of lignin in value added products. In this paper, we isolated pure lignin (ca. 98 % of purity) from elephant grass (Pennisetum purpureum) using two simple extractions with diluted acid and alkali solutions and prepared lignin and lignin acetate nanoparticles dispersed in water-basis by anti-solvent addition. Elephant grass in natura contains ca. 25 % of lignin, which could be converted into lignin nanoparticles with a 37 % yield. Spherical lignin and lignin acetate nanoparticles were revealed by electron microscopies (TEM and FESEM) and proved to be stable in a wide pH range (5–11) and ionic strength lower than 0.01. Lignin nanoparticles showed higher antioxidant activity (RSI of ca. 82) as compared to lignin in solution and to the commercial antioxidants (BHT and BHA). These nanoparticles were successfully incorporated in a neutral cream, resulting in a tinted sunscreen formulation with both ultraviolet and visible absorption. Altogether, we present here an effective method to isolate pure lignin from a non-food biomass and to prepare stable and highly antioxidant lignin nanoparticles that can be applied in dermocosmetics and are intrinsically non-toxic to the environment.

Between placebo and nocebo: Response to control treatment is mediated by amygdala activity and connectivity.

In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants' placebo/nocebo responding tendencies. In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre-post responses in the neutral control condition, and investigated (a) fMRI signal differences (post minus pre) between the two groups in neutral condition, and (b) seed-based resting state connectivity of the bilateral amygdala, known to be involved in emotional self-regulation, as well as ambiguous stimulus processing and aversive learning. The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre-post changes predicted behavioural placebo/nocebo response in this and two independent datasets. These findings suggest that measuring pre-post change in the neutral control condition might provide important information about subjects' individual differences in placebo/nocebo response. Pre-post changes in pain ratings in neutral conditions are modulated by amygdala activity and connectivity and can be used to predict placebo/nocebo responses.

Sorocea guilleminiana Gaudich.: Wound healing activity, action mechanisms, and chemical characterization of the leaf infusion.

Sorocea guilleminina Gaudich. is a tree or shrub endemic to Brazil. Its leaves are used in Brazilian folk medicine for the healing of wounds, stomach problems, inflammation and as diuretic. The present study evaluates the activity and action mechanisms of the healing properties of the aqueous extract of S. guilleminiana leaves (AESg), in experimental models in vivo and in vitro, as well as performs a phytochemical analysis of the extract. The AESg was prepared by infusion: Ten g of dry leaves powder in 1 L hot water, soaked for 15 min, filtered, lyophilized, and stored at -30 °C. Phytochemical analyses were realized by colorimetry and HPLC/ESI/MS. Its' in vitro cytotoxicity was evaluated on fibroblastic N3T3 cells. The potential of the wound healing activity in vivo was evaluated using excision and incision wound rat models, by histopathology of the injured skin along with the determination of nitric oxide, cytokines (IL-1β, IL-10, and TNF-α), and antioxidant parameters (GSH, MPO and CAT). In vitro wound healing activity was also demonstrated in scratched N3T3 cells, by measuring the proliferation/migration rate. The phytochemical analysis of the AESg revealed a strong presence of polar compounds, especially flavonoids (4 majoritarian), as well as terpenes and/or sterols (2 majoritarian). The AESg showed no toxicity in the N3T3 cell line (IC50 > 800 μg/mL). Topical treatment with the AESg showed an increase (p < 0.05) in wound contraction with 2 mg/g cream on days 5 and 9 (43.56% and 6.70% increase, respectively), and with 50 mg/g on days 7 and 9 (10.88% and 7.91%, respectively), compared to the vehicle (non-ionic neutral cream). Topical application of AESg (2 or 50 mg/g non-ionic cream) in incised wounds caused an increase in the force necessary for the rupture of the wound when compared to the vehicle group. No changes in cytokines (IL-1β, IL-10, or TNF-α) or NO accumulation was found with up to 50 mg/g AESg treatment. For antioxidant activity on the incision wound, an increase in GSH levels was denoted with the AESg use, at the lowest and highest dose (2 and 50 mg/g) by 75.86% and 61.20% respectively, when compared to the vehicle. Also, the CAT activity was accentuated by AESg at the highest dose (50 mg/g) by 85.87%. Finally, the AESg at all doses attenuated MPO activity significantly in the incision wound by 71.35%, 73.21%, 78.08%, respectively. In the scratch test on N3T3 cells, the treatment with AESg resulted also in an increase in fibroblast proliferation/migration rate, compared to the vehicle. AESg is not cytotoxic. The results confirm the popular use of the leaf infusion of S. guilleminiana for the treatment of cutaneous wounds, possibly by stimulating the proliferation of fibroblasts with a consequent deposition of collagen, fastening rearrangement of collagen fibers, and greater transformation into myofibroblasts, essential in the healing process. Preliminary chemical analyzes of AESg revealed the presence mainly of phenolic compounds, being salicylic acid, gallic acid, pinocembrin and isoquercitrin the majoritarian ones.

Study of antioxidant properties of thylakoids and application in UV protection and repair of UV-induced damage.

Skin is affected by environmental stress such as ultraviolet exposure. Topically applied antioxidants confer protection against this stress. Spinach thylakoid extracts are plant samples known as photosynthetic membranes containing antioxidant molecules able to dissipate excess of energy and oxidative stress. Antioxidant contents and activities were tested in thylakoid extracts stored for different periods at 4°C to compare their efficacities. Cytotoxicity of thylakoids was tested on human THP-1 cells along with the capacity to protect from oxidative stress using flow cytometry. Protection of thylakoids against ultraviolet was tested on engineered human skin using two formulations and evaluated by electronic microscopy. Results indicate that thylakoid extracts possess antioxidant molecules that were not significantly affected by storage at 4°C whereas photosynthetic activity was storage-dependent. Thylakoid extracts were not cytotoxic to human THP-1 cells, and three extracts protected cells against reactive oxygen species. Moreover, formulation comprising 0.1% or 0.01% of thylakoids and sunscreen provided a synergetic protection against UV exposure. Thylakoid extracts mixed with a neutral cream were also able to repair UV damages on engineered human skin. Thylakoid extracts contained various antioxidant molecules, and their properties were maintained in over storage at 4°C for more than 72months. Molecules and enzymes present in thylakoid extracts are involved in protecting and restoring the harmful effects of UV exposure. The involvement of antioxidant molecules such as carotenoids, SOD, and Fe-S clusters in cellular and regulatory metabolic reactions may explain the observed protective effects.

Effectiveness of aromatherapy massage on the stress of the surgical center nursing team: a pilot study.

To verify the effectiveness of aromatherapy with essential oils of lavender (Lavandula angustifolia) and geranium (Pelargonium graveolens) associated with massage for stress relief of a nursing staff of the surgical center through evaluation of biophysiological and psychological parameters. Pilot study, controlled and randomized clinical trial performed with the nursing team of a surgical center of a teaching hospital in the interior of the state of São Paulo. The intervention comprised six aromatherapy massages with essential oils diluted in neutral cream at concentration 1% each. Heart rate and blood pressure levels were measured before and after each massage session. The Work Stress Scale (WSS) and the List of Stress Symptoms (LSS) were applied before and at the end of the intervention. Statistical analysis was performed with the paired t-test and chi-square test, 95% confidence interval and p <0.05. There was a statistically significant reduction in heart rate and blood pressure levels after massage sessions. The use of aromatherapy has demonstrated effectiveness for lowering biophysiological parameters of the surgical center nursing staff. Brazilian Registry of Clinical Trials: RBR-6mgqn3.

Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy.

The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel "atopic march animal model"), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy.

Temporary deafferentation evoked by cutaneous anesthesia: behavioral and electrophysiological findings in healthy subjects.

Motor function and motor excitability can be modulated by changes of somatosensory input. Here, we performed a randomized single-blind trial to investigate behavioral and neurophysiological changes during temporary deafferentation of left upper arm and forearm in 31 right-handed healthy adults. Lidocaine cream was used to anesthetize the skin from wrist to shoulder, sparing the hand. As control condition, on a different day, a neutral cream was applied to the same skin area. The sequence (first Lidocaine, then placebo or vice versa) was randomized. Behavioral measures included the Grating Orientation Task, the Von Frey hair testing and the Nine-hole-peg-test. Transcranial magnetic stimulation was used to investigate short-interval intracortical inhibition, stimulus response curves, motor evoked potential amplitudes during pre-innervation and the cortical silent period (CSP). Recordings were obtained from left first dorsal interosseous muscle and from left flexor carpi radialis muscle. During deafferentation, the threshold of touch measured at the forearm was significantly worse. Other behavioral treatment-related changes were not found. The CSP showed a significant interaction between treatment and time in first dorsal interosseous muscle. CSP duration was longer during Lidocaine application and shorter during placebo exposure. We conclude that, in healthy subjects, temporary cutaneous deafferentation of upper and lower arm may have minor effects on motor inhibition, but not on sensory or motor function for the adjacent non-anesthetized hand.

Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids.

BackgroundThe acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD).ObjectiveWe performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity.MethodsFive groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream.ResultsOx-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration.ConclusionApplication of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.

Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially Inhibited by Acidification

Prolonged and/or repeated damage to the skin barrier followed by atopic dermatitis (AD) is an initial step in atopic march that ultimately progresses to respiratory allergy. Maintaining normal stratum corneum (SC) acidity has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. We determined whether a representative AD murine model, NC/Nga mice, develops airway inflammation after repeated epicutaneous application followed by inhalation of house dust mite (HDM), implying atopic march, and whether prolongation of non-proper SC acidity accelerates respiratory allergy. HDM was applied to the skin of NC/Nga mice, accompanied by the application of neutral cream (pH 7.4) or acidic cream (pH 2.8) for 6 weeks. Intranasal inhalation of HDM was administered daily during the last 3 days. Repeated epicutaneous applications followed by inhalation of HDM in NC/Nga mice induced an atopic march-like progression from AD lesions to respiratory allergy. Concurrent neutral cream treatment accelerated or aggravated the allergic inflammation in the skin and respiratory system, whereas an acidic cream partially alleviated these symptoms. Collectively, we developed an atopic march in NC/Nga mice by HDM application, and found that prevention of a neutral environment in the SC may be an interventional method to inhibit the march.

Topical acidic cream prevents the development of atopic dermatitis- and asthma-like lesions in murine model.

Long-standing or repeated skin barrier damage followed by atopic dermatitis (AD) is the initial step of the atopic march that eventually progresses to respiratory allergies. Maintenance of an acidic pH in the stratum corneum (SC) is an important factor for normal skin barrier function. We performed this study to determine whether an oxazolone (Ox)-induced AD murine model can develop airway inflammation by topical application and nasal inhalation of a house dust mite, Dermatofagoides pteronyssinus (Dp), which is a novel 'atopic march animal model', and whether an acidic SC environment, made by repeated application of acidic cream, can interrupt this atopic march. During repeated treatment with Ox and Dp to make an atopic march murine model, acidic cream (pH 2.8) and neutral cream (pH 7.4) adjusted by citric acid and sodium hydroxide mixed with vehicle were applied twice daily. Repeated treatment with Ox and Dp to hairless mice induced AD-like skin lesions followed by respiratory allergy, defining it as an atopic march model. Acidic cream inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. These results indicate that a novel atopic march animal model can be developed by repeated topical and nasal treatments with house dust mite on Ox-induced AD mice and that the acidification of SC could be a novel intervention method to block the atopic march.

Role of Increasing Vaginal Acidity in Histological Changes and Softening of the Cervix Prior to Dilatation in Perimenopausal Women

Background: cervical dilatation, along with hysteroscopy or endometrial curettage, is one of the most common procedures in gynecological practice. However, difficulty in entering the internal cervical os may be encountered; Therefore, there is a need for an effective cervical priming agent which can be used in general gynecological practice. Vaginal acidification might increase collagen degradation. It is known that cervical collagen degradation contributes to the ripening process. Aim of the work: the present study was designed to evaluate the efficacy of acidifying vaginal cream in cervical tissue remodeling and softening. Patients and methods: this study is a double-blinded clinical trial study, conducted in Obstetrics and Gynecology Department of Al-Azhar University hospital (Damietta). It included fifty perimenopausal women, their age ranged from 45-55ys, planned for cervical dilatation before endometrial biopsy due to irregular uterine bleeding. They were divided into two main groups: Group I: women who were treated with acidifying vaginal cream (Eva base cream melted with acetic acid 5%). Group II: women who were treated with neutral (placebo) vaginal cream (Eva base cream only). Efficacy of acidifying vaginal cream on the cervix was assessed on the basis of improved cervical softening and degree of cervical changes on the histological examination. Results: there was no significant difference in both groups during the preoperative assessment of the cervix and premedication. During operation in the study group (I) 1st Hegar’s passed was No8 in 52% of cases and No9 in 28% of cases denoting the significant effect of acetic acid on cervical dilation in comparison with placebo group (II)in which the cervix was closed in 44% of cases and Hegar’s No 3 passed in 36% of cases showing statistical significance between the two groups. As regards the histological examination, it was found that in group (I) collagen dissociation grade II represent 56% and grade III 24% with statistical significance in comparison with placebo group (II) in which collagen was grade 0, in 76% . Also, the inflammatory changes in group(I) showed moderate changes in 72% of cases and 20% showed severe changes with statistical significance in comparison with the control group(II) in which 56% of cases showed no inflammatory changes. Conclusion: vaginal acidification with 5% acetic acid as a cervical softening agent appeared to be safe, effective, with no adverse effects.

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat

We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection. We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier. Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene. After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 microg or 10 ng/kg) or locally as a thin layer (1.0 microg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice. Likewise, BPC 157 was effective given per-orally (0.16 microg/ml in the drinking water (12 ml/day/rat)) until sacrifice. Commonly, BPC 157 microg-ng-rats exhibited consistent functional, biomechanical, macroscopic and histological healing improvements. Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy.

In vivo Quantification of Acyclovir Exposure in the Dermis Following Iontophoresis of Semisolid Formulations

The objective was to quantify acyclovir (ACV) exposure in the dermis following iontophoresis of nontraditional (pH-11 gels) and traditional (neutral cream) topical formulations of ACV. Given that the application time of a formulation on the skin can be significantly reduced with iontophoresis, the use of formulations optimized for iontophoretic delivery was explored to maximize the delivery of ACV to the site of action for the treatment of Herpes-labialis. Microdialysis probes were inserted into the shaved skin of tranquilized rabbits. Iontophoresis was performed at a constant current density of 200µA/cm2 for 60min using a single-use drug cartridge filled with the following formulations: neutral cream, soluble fraction of the same cream (anodal and cathodal-current), or two formulations of pH-11 gels, one without and one with stabilizers and preservatives (cathodal-current). Results showed that only the ACV in the water phase of the cream is available for transport. All of the pH-11 gels exhibited a statistically significant (p<0.001) increase in ACV dermis exposure compared to the neutral cream formulations without any additional sign of skin irritation. In conclusion, iontophoresis of ACV pH-11 gels provides higher ACV concentrations in the dermis than iontophoresis of neutral cream formulations, which could result in a better clinical outcome.

Topical steroid application versus circumcision in pediatric patients with phimosis: a prospective randomized placebo controlled clinical trial

Topical steroids have been advocated as an effective alternative treatment to circumcision in boys with phimosis. We evaluated the effectiveness of topical steroid therapy compared to a placebo neutral cream in 240 patients with phimosis. A prospective study was carried out over a 24-months period, on an out-patient basis on two groups of patients with phimosis. One-hundred twenty patients applied a steroid cream twice a day for 4 weeks, and another group of 120 pts used a placebo cream twice a day for 4 weeks. Patients were assigned to either group by a computer-generated random choice. All patients in our series completed the two treatment periods without interruption. At a median follow-up of 20 months (6-30 months) therapeutic success was obtained in 43.75% (99/240) of cases, independently of the protocol. In particular, therapeutic success was obtained in 65.8% (79/120) of cases in the steroids group and in 16.6% (20/120) of cases in the placebo group, the difference being statistically significant (P < 0.0001, Mann-Withney test). Our study shows that topical steroids represent a good alternative to surgery in case of phimosis. Steroid therapy using monometasone furoate 0.1% in our series gave better results that placebo with an overall efficacy of 65.8%. In patients where a phimotic ring persist after steroid therapy, circumcision is mandatory.