Multicenter Clinical Trials Analyzing Efficacy and Safety of Topical Cortex Phellodendri Compound Fluid in Treatment of Diabetic Foot Ulcers.

BACKGROUND The aim of this study was to analyze the clinical application of cortex phellodendri compound fluid (CPCF) in the treatment of diabetic foot ulcers. MATERIAL AND METHODS From January 2012 to December 2015, a total of 720 cases of diabetic foot ulcers (DFU) were randomly assigned into an experimental group (n=540) that was treated by CPCF and a control group (n=180) that was treated by a Kangfuxin solution (KFS). After 4 weeks of treatment, their ulcer area, serum growth factor, clinical total effective rate, and incidence of adverse events were assessed. RESULTS There were 720 patients who completed the trial. The experimental group was superior to the control group in reducing ulcer area, increasing growth factor content, and total effective rate (P<0.05). There was no significant difference in the adverse events rates between the 2 groups. CONCLUSIONS CPCF external treatment of diabetic foot ulcer can promote ulcer healing and increase the concentration of growth factors, and it is safe and reliable.

Efficacy of frog skin lipids in wound healing.

BACKGROUND: Frog skin has been sequentially and scientifically evaluated by our group for its wound healing efficiency. Owing to the complex structure of skin, attempts were being made to analyse the role of individual constituents in different phases of healing. Our earlier papers have shown the significance of frog skin not only in wound healing but also enhancing the proliferating activity of the epidermal and dermal cells which are instrumental for normal healing process. We also have identified for the first time novel antimicrobial peptides from the skin of Rana tigerina and thereby reduce the complications involved in the sepsis. PURPOSE OF THE STUDY AND RESULTS: The current study envisages the role of frog skin lipids in the inflammatory phase of wound healing. The lipid moiety of the frog skin dominated by phospholipids exhibited a dose dependent acceleration of healing irrespective of the mode of application. The efficiency of the extract is attributed partially to the anti-inflammatory activity as observed by the histochemical and immunostimulatory together with plethysmographic studies. CONCLUSIONS: Thus, frog skin for the first time has been demonstrated to possess lipid components with pharmaceutical and therapeutic potential. The identification and characterization of such natural healing molecules and evaluating their mechanism of action would therefore provide basis for understanding the cues of Nature and hence can be used for application in medicine.

Agents for the decolonization of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are a common cause of hospital- and community-acquired infections. Persons may have asymptomatic colonization with MRSA in the nares, axillae, perineum, or groin. Since MRSA colonization often precedes infection, and infection is associated with significant morbidity and mortality, there is great interest in preventing the transmission of MRSA and decolonizing persons who harbor these bacteria. We provide an evidence-based review of MRSA decolonization agents. Our search strategy included the databases of the Cochrane Central Register of Controlled Trials, MEDLINE (1962-May 2008), and EMBASE (1980-May 2008). To identify unpublished trials, abstract books from appropriate major scientific meetings were hand searched, manufacturers were contacted, and pharmacology references were researched for available commercial products, formulations, adverse events, and dosing. The most extensive research in MRSA decolonization has been conducted with mupirocin, which is applied to the anterior nares 2-3 times/day for 5 days. Increased use is correlated to resistance development; therefore, routine decolonization is not prudent unless MRSA colonization is confirmed in the nares or other site. Retapamulin is under investigation for use in nares decolonization. If total body decolonization is necessary, bathing or showering with an antiseptic agent such as chlorhexidine gluconate is recommended in combination with mupirocin applied to the nares to improve the likelihood of eradication. Oral antibiotics have been evaluated for use in decolonization of the skin and nares but should be considered only in conjunction with topical agents and when all other decolonization attempts and environmental controls have been exhausted. Homeopathic and investigational agents may also be effective. Although mupirocin is the standard of care for decolonization of MRSA, several agents demonstrate efficacy and many merit further investigation.

Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies.

BACKGROUND: One of the cardinal principles of homeopathy is the "law of similarities", according to which patients can be treated by administering substances which, when tested in healthy subjects, cause symptoms that are similar to those presented by the patients themselves. Over the last few years, there has been an increase in the number of pre-clinical (in vitro and animal) studies aimed at evaluating the pharmacological activity or efficacy of some homeopathic remedies under potentially reproducible conditions. However, in addition to some contradictory results, these studies have also highlighted a series of methodological difficulties.The present study was designed to explore the possibility to test in a controlled way the effects of homeopathic remedies on two known experimental models of acute inflammation in the rat. To this aim, the study considered six different remedies indicated by homeopathic practice for this type of symptom in two experimental edema models (carrageenan- and autologous blood-induced edema), using two treatment administration routes (sub-plantar injection and oral administration). METHODS: In a first phase, the different remedies were tested in the four experimental conditions, following a single-blind (measurement) procedure. In a second phase, some of the remedies (in the same and in different dilutions) were tested by oral administration in the carrageenan-induced edema, under double-blind (treatment administration and measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague Dawley rats weighing 170-180 g were used. Six homeopathic remedies (Arnica montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested. Edema was measured using a water-based plethysmometer, before and at different times after edema induction. Data were analyzed by ANOVA and Student t test. RESULTS: In the first phase of experiments, some statistically significant effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the reduction in paw volume increase ranging from 10% to 28% at different times since edema induction). In the second phase of experiments, the effects of homeopathic remedies were not confirmed. On the contrary, the unblinded standard allopathic drug indomethacin exhibited its anti-inflammatory effect in both experimental phases (the reduction in paw volume increase ranging from 14% to 40% in the first phase, and from 18% to 38% in the second phase of experiments). CONCLUSION: The discrepancies between single-blind and double-blind methods in animal pharmacological research are noteworthy and should be better investigated, also in non-homeopathic research.

Systematic review of treatments for atopic eczema.

BACKGROUND: Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done. OBJECTIVES: The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods. DATA SOURCES: Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies. INCLUSION/EXCLUSION CRITERIA: Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included. DATA EXTRACTION: Data extraction was conducted by two observers onto abstraction forms, with discrepancies resolved by discussion. QUALITY ASSESSMENT: The quality assessment of retrieved RCTs included an assessment of: a clear description of method and concealment of allocation of randomisation, the degree to which assessors and participants were blinded to the study interventions, and whether all those originally randomised were included in the final main analysis. DATA SYNTHESIS: Where possible, quantitative pooling of similar RCTs was conducted using the Cochrane Collaboration's methods. Where statistical heterogeneity was found, sources of heterogeneity in terms of study participants, formulation or posology of intervention, and use of co-treatments were explored. Where pooling was not deemed to be appropriate, detailed descriptions of the study characteristics and main reported results were presented along with comments on study quality. RESULTS: A total of 1165 possible RCTs were retrieved in hard copy form for further scrutiny. Of these, 893 were excluded from further analysis because of lack of appropriate data. The 272 remaining RCTs of atopic eczema covered at least 47 different interventions, which could be broadly categorised into ten main groups. Quality of reporting was generally poor, and limited statistical pooling was possible only for oral cyclosporin, and only then after considerable data transformation. There was reasonable RCT evidence to support the use of oral cyclosporin, topical corticosteroids, psychological approaches and ultraviolet light therapy. There was insufficient evidence to make recommendations on maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, topical coal tar and topical doxepin. (ABSTRACT TRUNCATED)

Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women.

OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.

The safety of low-dose Larrea tridentata (DC) Coville (creosote bush or chaparral): a retrospective clinical study.

OBJECTIVE: To determine whether internal use of low doses of Larrea tridentata tincture or topical applications of this traditional herbal medicine are safe. DESIGN: Retrospective review of all people prescribed Larrea for internal or for topical use over a 22-month period. SETTING/LOCATION: A general naturopathic practice in Sedona, Arizona. SUBJECTS: Thirteen patients were identified for whom Larrea tincture for internal use was prescribed. An additional 20 female and 3 male patients were identified for whom an extract of Larrea in Ricinus communis (castor) oil for topical use was prescribed. No patient had any history of liver disease. INTERVENTIONS: Larrea was prescribed as part of the usual care of each patient. In all cases it was given as either part of a complex herbal formula individualized for each patient containing less than 10% Larrea tincture or as an extract in Ricinus oil for topical use. OUTCOME MEASURES: Serum liver enzyme levels as well as blood urea nitrogen and creatinine levels, glucose levels, electrolytes, bilirubin levels, iron levels, ferritin levels, lipid levels, and complete blood count (CBC) were available for analysis in four patients; general clinical history and physical examination findings were relied on in all other cases. RESULTS: The four patients with complete before and after blood chemistry panels and CBC had no indication of liver damage from use of Larrea. This included one patient who was taking medications with significant potential for hepatotoxicity. No patient in the study, whether using Larrea for short term or long, internally or externally, showed any sign of organ damage during the period of follow-up. CONCLUSIONS: Relatively small intakes of Larrea tincture, or topical application of extracts in Ricinus oil, are safe when prescribed by a clinically trained botanical prescriber. Larrea should be used with caution in persons with a history of previous, or current, liver disease. It may be preferable to avoid the use of Larrea capsules because they have been associated with potentially dangerous overdosing.

Cationic topical formulations tested in high dilutions offers protective effects in fibroblast cells culture

Topical administration is a simple and comfortable form of cutaneous administration of drugs. However, in this route of administration the drug needs to overcome the barrier posed by the skin to reach an effective concentration. For this reason, many topical formulations are developed with a cationic component. The promotion of absorption occurs due to the disruption of the stratum corneum. But this cationic component has also high irritating potential to the skin. The biotherapics are medicines prepared from a toxic product or etiologic agent, following the homeopathic pharmacopoeia technique, and they are used mainly in cases of hipersensitization. In this experiment, high dilutions (HD) obtained from a cationic formulation were prepared and evaluated considering cell viability in “in vitro” mouse fibroblast (L929) culture cells model by a colorimetric MTT assay. No signs of toxicity were observed, which demonstrates the safety of these HD preparations to the healthy cells. The effectiveness of these HD was also investigated in cells damaged by cationic formulations. The results demonstrated that the HD 30c was the most effective preparation in preventing the cell damage caused by the tested irritating product, increasing cell viability from 56.6% (damaged cells) to 100% (similar to negative control group, p>0.05). These results provide evidence of the positive action of high dilutions against the exposure to a cytotoxic agent. (AU)

Cationic topical formulations tested in high dilutions offers protective effects in fibroblast cells culture

Topical administration is a simple and comfortable form of cutaneous administration of drugs. However, in this route of administration the drug needs to overcome the barrier posed by the skin to reach an effective concentration. For this reason, many topical formulations are developed with a cationic component. The promotion of absorption occurs due to the disruption of the stratum corneum. But this cationic component has also high irritating potential to the skin. The biotherapics are medicines prepared from a toxic product or etiologic agent, following the homeopathic pharmacopoeia technique, and they are used mainly in cases of hipersensitization. In this experiment, high dilutions (HD) obtained from a cationic formulation were prepared and evaluated considering cell viability in “in vitro” mouse fibroblast (L929) culture cells model by a colorimetric MTT assay. No signs of toxicity were observed, which demonstrates the safety of these HD preparations to the healthy cells. The effectiveness of these HD was also investigated in cells damaged by cationic formulations. The results demonstrated that the HD 30c was the most effective preparation in preventing the cell damage caused by the tested irritating product, increasing cell viability from 56.6% (damaged cells) to 100% (similar to negative control group, p>0.05). These results provide evidence of the positive action of high dilutions against the exposure to a cytotoxic agent.

Reliéva, a Mahonia aquifolium extract for the treatment of adult patients with atopic dermatitis.

This clinical study was conducted to determine the efficacy and safety of Reliéva cream in adult patients with atopic dermatitis (eczema). This was an open-label trial in 42 patients with atopic dermatitis treated for 12 weeks with Reliéva cream (a homeopathic product containing Psorberine, a proprietary Mahonia aquifolium extract). Efficacy and safety was assessed using Eczema Area and Severity Index scores and a Subject Reported Evaluation of Treatment. The results showed significant (P < 0.05) improvements with respect to Eczema Area and Severity Index scores by comparison to subjects' baseline scores. In addition, subjects responding to a posttreatment evaluation questionnaire indicated a substantial benefit when rating effectiveness, itching, and appearance as a result of using the study preparation. Reliéva cream appears to be a safe and effective treatment for adult patients with atopic dermatitis (eczema).

Homoeopathy for the treatment of lichen simplex chronicus: a case series.

Twenty-seven patients with chronic lichen simplex involving various parts of the body were treated. Hydrocotyle was prescribed to 21 patients in different potencies (6c, 30c, 200c, 1 M, 10 M), Thuja to three patients (1 M, 10 M), Graphites (6c), Kali bich (30c) and Sulphur (200c) to one patient each during 1 year study period. Only two patients showed complete improvement with Thuja and one with Graphites. In other cases, the response was limited to partial relief of [corrected] itching.

Appetoff: another diet fad.

Appetoff diet patches were diet aids introduced to the public in 1987 and removed from the market in 1988 by the FDA for reasons of fraud. The ingredients were supposedly homeopathic concentrations of plant and mineral products. Although 91.6% of persons in this study who used the product for at least 1 week reported weight loss and mild side effects, no active ingredients could be detected by gas chromatography/mass spectrometry.

The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: a multi-centre, randomised, double-blind comparative clinical trial.

Acute low back pain is a very common condition in Western industrialised countries. In most cases analgesics or topical medications are prescribed at first encounter with the general practitioner (GP). The aim of this study was to investigate whether the homeopathic gel Spiroflor SRL gel (SRL) is equally effective and better tolerated than Cremor Capsici Compositus FNA (CCC) in patients with acute low back pain. A multi-centre, randomised, double-blind, controlled clinical trial was conducted in the practices of 19 GPs in the districts of Bristol and Manchester, UK. One hundred and sixty-one subjects suffering from acute low back pain were treated for one week either with SRL or with CCC. Pain was scored on a 100 mm visual analogue scale (VAS). Main efficacy parameter VAS reduction was compared between treatments. Evaluation of safety was primarily based on the number of subjects with adverse events (AEs), withdrawals due to an AE and adverse drug reactions (ADRs). The mean difference between the VAS reduction in the SRL group and the CCC group adjusted for VAS at baseline and age was -0.6mm (90% CI = -6.5-5.3mm). Fewer subjects in the SRL group (11%) experienced an AE than in the CCC group (26%). The same applies to the number of subjects with an ADR (3/81 = 4% vs 18/74 = 24%) and the number of subjects withdrawn due to an ADR (0/81 = 0% vs 8/74 = 11%). In conclusion, SRL and CCC are equally effective in the treatment of acute low back pain, however, SRL has a better safety profile. Spiroflor SRL gel is preferable to Capsicum-based products for the topical treatment of low back pain, because of the lower risk of adverse effects.

Experimental human infection with the dog hookworm, Ancylostoma caninum.

OBJECTIVE: To investigate possible routes for human infection by the dog hookworm (Ancylostoma caninum). DESIGN, SETTING AND PARTICIPANT: Relatively small numbers of infective larvae were administered orally and percutaneously to an informed healthy volunteer (J K L) under medical supervision, at intervals between May 1998 and May 1999. MAIN OUTCOME MEASURES: Symptoms; weekly blood eosinophil counts; faecal microscopy. RESULTS: A marked blood eosinophilia followed a single oral exposure to 100 infective larvae, while faecal examination remained negative. Eosinophil counts then declined gradually, although a rapid, spontaneous rise several months later, at the beginning of spring, possibly indicated reactivation of dormant larvae. Blood eosinophil numbers did not rise significantly after percutaneous infection with 200 larvae. A subsequent, smaller, oral inoculum of 20 larvae provoked an eosinophil response similar to that of the first experiment. CONCLUSIONS: Our findings suggest that, following ingestion, some infective larvae of A. caninum develop directly into adult worms in the human gut (as they do in dogs). While the percutaneous route might be the most common means of human exposure to canine hookworm larvae, leading generally to subclinical infection, oral infection may be more likely to provoke symptomatic eosinophilic enteritis.

Examination of the cutaneous absorption of copper after the use of copper-containing ointments.

Because copper-containing ointments are frequently used in anthroposophical medicine, a phase I trial to investigate the cutaneous absorption of copper was conducted. Sixty-one volunteers were randomized [group A: 0.4% copper (I) oxide, 13 men and 18 women (19-55 years); group B: 20% elementary copper, 11 men and 19 women (18-70 years)]. The ointment was applied over a 4-week period followed by a 4-week wash-out phase. Serum and urine copper concentrations were measured by atomic absorption spectrometry and hair copper concentration by inductive coupled plasma mass spectrometry. For statistical analysis, the Student t test for related random samples was used; alpha = 0.05 was chosen for the standard error. In group A, an increase of copper in serum and scalp hair and a decrease in urine were found in the study period. The mean serum concentration in all premenopausal women using oral contraceptives was above normal. In group B, the serum copper concentration increased significantly; in urine, it decreased, and in scalp hair, it remained stable. A higher level of serum copper was found in female volunteers using hormonal contraception. Treatment with the 2 different ointments did not cause toxic irritations on the skin, and it can therefore be deduced that the appropriate application of ointment preparations containing copper in concentrations up to 20% do not present a toxic risk.