Antiherpetic activity of the traditionally used complex essential oil Olbas.

Essential oils of medicinal plants are increasingly of interest as novel drugs for antiherpetic agents, since herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. The antiviral effect of Olbas, a traditionally used complex essential oil, and of cajuput oil, a major constitutent of Olbas, against HSV type 1 was examined. The antiviral activity of these essential oils was tested in vitro on monkey kidney cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of Olbas and cajuput oil for herpes simplex virus plaque formation was determined at 1.8 microg/ml and 7.5 microg/ml, respectively. At noncytotoxic concentrations of these oils, plaque formation was significantly reduced by 99% for Olbas and 66% for cajuput oil. The selectivity index of 150 for Olbas against herpes simplex virus was superior to a rather low selectivity index for cajuput oil. The mode of antiviral action of these essential oils was assessed by time-on-addition assays. Herpesvirus was significantly inhibited by pretreatment with Olbas essential oil prior to infection of cells. These results indicate that Olbas affected the virus before adsorption, but not after penetration into the host cell, thus Olbas exerted a direct antiviral effect on HSV. A clearly time-dependent antiviral activity for Olbas and cajuput oil could be demonstrated. Considering the lipophilic nature of the Olbas complex essential oil mixture, which enables it to penetrate the skin, and a high selectivity index, Olbas might be suitable for topical treatment of herpetic infections.

Comparative study on the in vitro human skin permeation of monoterpenes and phenylpropanoids applied in rose oil and in form of neat single compounds.

Essential oils are ingredients of cosmetic and health care products as well as massage oil used in aromatherapy. There is no doubt that essential oils and their components are able to permeate human skin. But information is rare dealing with percutanous absorption of essential oils in more detail. In this paper we investigated the in vitro skin permeation of monoterpenes and phenylpropanoids applied in pure rose oil and in form of neat single substances. We found that the application form had an exceeding influence on the skin permeation behaviour of the compounds. For substances applied in rose oil a clear relationship between their lipophilic character, chemical structure, and skin permeation could be confirmed. Regarding the P(app)-values the substances are ranked in the order: monoterpene hydrocarbons < monoterpene alcohols < monoterpene ketons < phenylpropanoids. In contrast, for neat single substances there were no relationships between their lipophilic characters, structures and skin permeation. Furthermore, except for alpha-pinene and isomenthone, the P(app)-values of all other substances were several times higher when applied in pure native rose oil than in their neat form. This suggests that co-operative interactions between essential oil components may promote skin permeation behaviour of essential oil and its components.

Comparative study on the cytotoxicity of different Myrtaceae essential oils on cultured vero and RC-37 cells.

Medicinally and commercially important essential oils from the family Myrtaceae, i.e. cajuput, clove, kanuka and manuka were phytochemically analysed by GC-MS. Cytotoxicity of these essential oils was evaluated in a standard neutral red assay. Maximum noncytotoxic concentrations for cajuput oil and clove oil were determined at 0.006%, kanuka oil and manuka oil were more cytotoxic with a maximum noncytotoxic concentration of 0.001%. The compounds alpha-pinene, eugenol and leptospermone demonstrated maximum noncytotoxic concentrations at dilutions of 0.001%, 0.003% and 0.001%, respectively. However, the terpene 1,8-cineole was about 100 times less toxic to cultured cells with a maximum noncytotoxic concentration of 0.1% and a TC50 value of 0.44%. Manuka essential oil exhibited high levels of virucidal activity against HSV-1 as well against drug-resistant HSV-1 isolates in viral suspension tests. Determination of cytotoxicity of natural products is an important prerequisite for application in cosmetic and health care products and in antiviral tests.

Topical tea tree oil effective in canine localised pruritic dermatitis--a multi-centre randomised double-blind controlled clinical trial in the veterinary practice.

Tea tree oil, a volatile oil, is well known for its broad antibacterial and antifungal activity. A standardised and stabilised 10% tea tree oil cream was tested against a commercial skin care cream (control cream) in the management of canine localised acute and chronic dermatitis. Fifty-seven dogs with clinical manifestations of mostly pruritic skin lesions or alterations, skin fold pyodermas and other forms of dermatitis, corroborated by predominantly positive fungal and bacterial skin isolates, were enrolled by seven practising veterinarians and randomly allocated to two study groups (28:29) and were treated twice daily with a blinded topical preparation. After 10 days of treatment, success rates of 71% for the tea tree oil cream and 41% for the control cream (over-all efficacy documented by the veterinary investigator) differed significantly (p = 0.04), favouring tea tree oil cream treatment. Accordingly on day 10, the tea tree oil cream caused significantly faster relief than the control cream (p = 0.04) for two common clinical dermatitis signs, pruritus (occurring in 84 % of dogs) and alopecia. Only one adverse event was reported in the tea tree oil group (suspected not to be causally related to the study drug) and none in the control cream group. The tested herbal cream appears to be a fast-acting safe alternative to conventional therapy for symptomatic treatment of canine localised dermatitis with pruritus.

Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis.

Hormone replacement therapy is contraindicated in women with breast cancer. Extracts from the rhizomes of Cimicifuga racemosa, have gained acceptance as a natural alternative for the treatment of menopausal symptoms. In the present study we investigated the antiproliferative activity of C. racemosa extracts (isopropanolic and ethanolic) on the estrogen receptor positive MCF-7 and estrogen receptor negative MDA-MB231 breast cancer cells by WST-1 assay. Down regulation of the proliferative activity and cell killing by isopropanolic and ethanolic extracts occurred in a clear dose-dependent response with a 50% growth inhibitory concentration of 54.1 +/- 11.4 and 80.6 +/- 17.7 micro g/ml in MCF-7 cells and of 29.5 +/- 3.0 and 58.6 +/- 12.6 microg/ml in MDA-MB231 cells, respectively. Further, the mode of cell death was identified as apoptosis by microscopic inspection and confirmed by light scatter characteristics and by detection of Annexin V adherence to phosphatidylserine by flow cytometry. In addition, the involvement of activated caspases was supported by the cleavage of cytokeratin 18 detected with M30 antibody. Increases in the level of M30-antigen of about 4-fold and 2-fold over untreated controls were observed in C. racemosa -treated MCF-7 and MDA-MB231 cells. These results indicate that C. racemosa extract exerts no proliferative activity, but kills the estrogen receptor positive MCF-7 as well as estrogen receptor negative MDA-MB231 cells by activation of caspases and induction of apoptosis.

Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro.

The virucidal effect of peppermint oil, the essential oil of Mentha piperita, against herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for HSV-1 and HSV-2, respectively. Peppermint oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 82% and 92% for HSV-1 and HSV-2, respectively. Higher concentrations of peppermint oil reduced viral titers of both herpesviruses by more than 90%. A clearly time-dependent activity could be demonstrated, after 3 h of incubation of herpes simplex virus with peppermint oil an antiviral activity of about 99% could be demonstrated. In order to determine the mode of antiviral action of the essential oil, peppermint oil was added at different times to the cells or viruses during infection. Both herpesviruses were significantly inhibited when herpes simplex virus was pretreated with the essential oil prior to adsorption. These results indicate that peppermint oil affected the virus before adsorption, but not after penetration into the host cell. Thus this essential oil is capable to exert a direct virucidal effect on HSV. Peppermint oil is also active against an acyclovir resistant strain of HSV-1 (HSV-1-ACV(res)), plaque formation was significantly reduced by 99%. Considering the lipophilic nature of the oil which enables it to penetrate the skin, peppermint oil might be suitable for topical therapeutic use as virucidal agent in recurrent herpes infection.

[St. John' Wort (Hypericum perforatum L.)--multicompound preparations versus single substances]. / Johanniskraut (Hypericum perforatum L.)--Vielstoffgemische kontra phytogene Einzelstoffe.

Aqueous alcoholic extracts of St. John s wort are used for the treatment of mild to moderate depression. Recently, Hypericum extracts were also shown to inhibit the growth of various human malignant cells. We promote the hypothesis that the various biological activities of aqueous Hypericum extracts are based on synergistic interactions of all compounds present therein and not on the pharmacological activities of single compounds.

[St. John's Wort (Hypericum perforatum): a plurivalent raw material for traditional and modern therapies]. / Johanniskraut (Hypericum perforatum): Ein plurivalenter Rohstoff für traditionelle und moderne Therapien.

St. John's Wort is one of the oldest and one of the best experimentally and clinically examined herbal remedies. In various medical cultures and medical systems--that is to say the regions of origin of Hypericum perforatum, like Europe, West Asia and North Africa--St. John's Wort has been used as a remedy for centuries. Preparations from St. John's Wort not only represent medical traditions but also ways of thinking, ideas and experiences from naturopathic healers (non-physicians) as well as patients. The complex multicompound with its evolutionary and coevolutionary developed composition and structure acts as a varied raw material for the production of quantitative and qualitative dissimilar remedies, which are multicompounds themselves. They differ not only analytically but also quite often in their effects. The certain and potential spectrum of internal and external uses includes gastrointestinal complaint and illness, skin disease, mucosal lesion, superficial injury, depressive upset and depression, somatoform disorders, restlessness, nervosity, convalescence, exhaustion, sleep disturbance and nursing treatment. The plurivalent character of the multicompound even enables a broad spectrum of activity. This might justify to prefer St. John's Wort to other drugs in a wide range of treatments: In tumor patients with depression the antioxidative effect and the experimentally documented induction of apoptosis could mean an additional advantage, and in depressive patients with coronary heart disease the same applies to the anti-inflammatory and antioxidative effects.

Review of laparoscopic and open colorectal surgery in the "Zitha" Hospital (Luxembourg) in the year 2002.

BACKGROUND: A review and outcome of laparoscopic colorectal surgery in the visceral surgery unit in the Zitha Hospital for the year 2002. METHODS: All patients, presenting with benign or malignant disease of the colon or rectum were evaluated. Depending on the tumour size, a laparoscopic approach is advocated whenever possible. Operation and patient specific factors (age, duration of the procedure and duration of hospital stay, diagnosis of malignant tumour versus benign disease, conversion and complication rate) are presented. Patients who had to be converted are classified under the open surgery group. RESULTS: A total of 103 laparoscopic or open procedures on the colon/rectum were performed between the 1st of January 2002 and the 31st of December 2002. 74% were treated by a laparoscopic and 26% by an open approach. 10 out of 103 patients did not undergo a colonic resection but instead an emergency colostomy/ ileostomy or oversewing of a bowel leak, in 8 cases performed laparoscopically. 44 patients have been operated for a benign disease (36 laparoscopic and 8 open procedures) and 59 patients have been treated for a malignant disease (40 laparoscopic and 19 open procedures). The average operating time for the laparoscopic resection was 160 minutes in comparison to 182 minutes for the open resection. The conversion rate (inclusive of non-resection procedures) was 5% for a benign disease and 11% for colorectal cancer. The minor complication rate was 16% in laparoscopic surgery and 30% in open surgery. We saw two major complications in both the open and laparoscopic groups (4%). Reoperation was necessary in one patient out of 103. The average postoperative hospital stay was 7.78 days for the laparoscopic and 16.6 days for the open group. The hospital mortality was 2.9%. CONCLUSION: The laparoscopic colorectal resection is a safe and beneficial procedure for the patient when used in experienced hands.

[Adverse effects and interactions of phytotherapeutic drugs]. / Unerwünschte Wirkungen und Wechselwirkungen von Phytotherapeutika.

The significantly increased sales figures many phytopharmaceuticals have achieved during the last years prove the confidence that a great part of the population has in herbal remedies. This is primarily due to the wide-spread opinion that herbal remedies are free from side-effects. The long tradition and presumed 'natural' origin are no guarantee for safety in the treatment with herbal remedies. Even if a large proportion of the undesirable events is traceable to falsifications, impurities and lacking quality controls, herbal drugs with controlled quality should not be generally classified as harmless. In the meantime it has been possible to prove the presence of active substances with toxic and cancerogenic properties in various phytopharmaceuticals. Interactions with other drugs have been documented in a number of notes, where phytopharmaceuticals could influence the blood plasma level of various drugs, presumably by activating or inhibiting the cytochrom-P450-system. At present, especially data about adverse effects during long-term administration of herbal remedies are under-represented. Particularly because of their presumed harmlessness they often are prescribed in the case of chronic diseases and then taken over a longer period of time. The frequency of undesirable effects of phytopharmaceuticals is remarkably low, even if the present lack of data about side-effects is considered.

Aqueous ethanolic extract of St. John's wort (Hypericum perforatum L.) induces growth inhibition and apoptosis in human malignant cells in vitro.

Extracts of Hypericum perforatum (St. John's wort) are widely and effectively used in the treatment of mild to moderate depression. In addition, hypericin, a component of Hypericum p. extracts, exhibits light-dependent phototoxic properties and can be used in phototherapy. We therefore investigated the cytotoxic activity of two total Hypericum p. extracts, namely from fresh and dried plants in the dark and after exposure to 7.5 J/cm2 white light illumination and compared it with the effect of hypericin on K562, U937, LN229 glioblastoma cell lines and normal human astrocytes. The chemical toxicity of non-illuminated Hypericum p. extracts in the cells tested is low as expressed by a LC50 between 1.9-4.1 mg/ml, which corresponds to 10.3-17.3 microM hypericin and 114.4-190.7 microM hyperforin after 48 h treatment. Hypericum p. extracts induced dose-dependent growth arrest of human malignant cells in the absence of illumination with GI50 values between 0.43-1.77 mg/ml (2.3-9.7 microM hypericin, 26.1-106.7 microM hyperforin) for the fresh plant extract and 0.59-3.03 mg/ml (2.5-12.8 microM hypericin, 24.2-124.7 microM hyperforin) for the dried extract. The growth inhibitory effect of fresh Hypericum p. extract was more pronounced in leukemia cell lines K562 and U937, the GI50 concentrations being about 7-fold lower than the corresponding LC50 for the cell lines K562 and U937, but almost the same as the LC50 for LN229 and NHA cells. GI50 (microgram/ml) for tumor cell lines K562 and U937 (432 and 799) established after 48 h differed significantly (p < 0.05) from those of LN229 and normal human astrocytes (1767 and 2900). The light-exposed extracts were more toxic, their LC50 and GI50 values were reduced to values corresponding to LC50 concentration of 3.7-7.4 microM and a GI50 of 1.3-3.5 microM for phototoxic hypericin. After exposure to light, there was a significant difference (p = 0.006) between the GI50 of glioblastoma LN229 cells (582 micrograms/ml) and normal human astrocytes (1050 micrograms/ml). Morphological examination by light microscopy and phosphaditylserine exposure on the outer plasma membrane investigated by Annexin V-binding with flow cytometry after 24 h confirmed that Hypericum p. extracts caused apoptosis of treated cells without exposure to light. Hypericum p. extracts derived from fresh herbs and from dried herbs which differ in their levels of phloroglucinols (hyperforin and adhyperforin) were compared. The hyperforin content of fresh St. John's wort extract exceeded that of dried plant extract by 47% and the GI50 values of fresh plant extract were 73%, 77% and 58% of those established for dried extract in the three malignant cell lines K562, U937 and LN229 in the dark (p < 0.05). Under white light (7.5 J/cm2), both extracts exerted comparable growth inhibitory and apoptosis inducing effects due to the phototoxicity of hypericin, the corresponding concentrations of which were in the range of 1.3-3.5 microM. The data reported in this study suggest that illumination is not essential for the growth inhibitory and apoptotic effects of Hypericum p. extracts, but light activation potentiates them. Furthermore, the constituent hyperforin is at least partly responsible for these effects in the dark.

Phytotherapy of chronic dermatitis and pruritus of dogs with a topical preparation containing tea tree oil (Bogaskin).

Localised dermatitis, for example unspecific eczema or skinfold pyoderma, is a very common diagnosis in dogs. Typical and impressive complaints are pruritus, erythema, erosion and oozing surface. With respect to the underlying disease dermatological treatment is indicated, usually based on antimicrobial and antipruriginous active substances, it can include transient glucocorticoids. An effective and safe alternative might be a phytotherapeutic topical preparation containing tea tree oil. Tea tree oil exerts both antimicrobial and antipruriginous effects. In an open multicenter study efficacy and safety of a standardized 10% tea tree oil cream applied thinly and twice daily for 4 weeks was tested in 53 dogs with chronic dermatitis, particularly non-specific eczema, allergic dermatitis, interdigital pyoderma, acral lick dermatitis and skinfold pyoderma. Analysis of efficacy assessed by investigating veterinarians showed a good or very good response to treatment for 82% of the dogs, significant at a 5% level (p = 0.05). At the end of the study a strong and significant reduction (p = 0.001) as well as disappearance of major symptoms were observed. Only two adverse events (local reactions) possibly related to tea tree oil occurred during therapy. Consequently the tested study medication (Bogaskin) can be considered an alternative for uncomplicated and localised dermatitis in dogs. Bogaskin might allow reduction of other pharmaceutical products, perhaps even replace standard therapy.

Antifungal effect of Australian tea tree oil on Malassezia pachydermatis isolated from canines suffering from cutaneous skin disease.

The lipophilic yeast Malassezia pachydermatis is part of the normal skin flora of most warm-blooded organisms. In a number of surveys it could be demonstrated that this yeast species might be involved in different skin diseases like seborrhoeic dermatitis, especially in dogs and cats. In order to look for an alternative therapeutic agent to the commonly used antimycotic and antiseptic synthetic substances the in vitro activity of Australian tea tree oil, the essential oil of Melaleuca alternifolia, against several strains of Malassezia pachydermatis was examined. All tested strains showed remarkably high susceptibility to tea tree oil. With these results the excellent antibacterial activity of tea tree oil is extended to a new group of fungal pathogens colonizing mainly mammals' skin. During the last ten years there was an increasing popularity of tea tree oil containing human health care products. The presented data open up new horizons for this essential oil as a promising alternative agent for topical use in veterinary medicine as well.

Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes simplex virus in cell culture.

The antiviral effect of Australian tea tree oil (TTO) and eucalyptus oil (EUO) against herpes simplex virus was examined. Cytotoxicity of TTO and EUO was evaluated in a standard neutral red dye uptake assay. Toxicity of TTO and EUO was moderate for RC-37 cells and approached 50% (TC50) at concentrations of 0.006% and 0.03%, respectively. Antiviral activity of TTO and EUO against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of TTO for herpes simplex virus plaque formation was 0.0009% and 0.0008% and the IC50 of EUO was determined at 0.009% and 0.008% for HSV-1 and HSV-2, respectively. Australian tea tree oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of TTO plaque formation was reduced by 98.2% and 93.0% for HSV-1 and HSV-2, respectively. Noncytotoxic concentrations of EUO reduced virus titers by 57.9% for HSV-1 and 75.4% for HSV-2. Virus titers were reduced significantly with TTO, whereas EUO exhibited distinct but less antiviral activity. In order to determine the mode of antiviral action of both essential oils, either cells were pretreated before viral infection or viruses were incubated with TTO or EUO before infection, during adsorption or after penetration into the host cells. Plaque formation was clearly reduced, when herpes simplex virus was pretreated with the essential oils prior to adsorption. These results indicate that TTO and EUO affect the virus before or during adsorption, but not after penetration into the host cell. Thus TTO and EUO are capable to exert a direct antiviral effect on HSV. Although the active antiherpes components of Australian tea tree and eucalyptus oil are not yet known, their possible application as antiviral agents in recurrent herpes infection is promising.

Effect of Australian tea tree oil on the viability of the wall-less bacterium Mycoplasma pneumoniae.

In vitro assays using a variety of essential oils revealed a particularly high antibacterial effect of Australian tea tree oil (TTO) on a great number of gram-negative and gram-positive bacteria of unrelated phylogenetic origin. In the present study, the susceptibility of cell wall-less bacteria such as the human pathogenic bacterium Mycoplasma pneumoniae to Australian tea tree oil was examined. The minimum inhibitory concentration (MIC) was determined to be 0.006% (v/v) TTO for the wild type and to 0.003% (v/v) TTO for mutants of M. pneumoniae which lost the ability to adhere to host cells (cytadherence-negative). The MIC and the MBC (minimum bactericidal concentration) for M. pneumoniae are 100 times lower than those for all other eubacteria tested. Electron microscopy with negatively stained cells as well as with ultrathin sections revealed a tendency to ovoid or round cells after oil treatment whereas the untreated cells of the wild type exhibit a flask-shaped morphology with a tip-like structure at one pole of the cell. The integrity of the mycoplasmal membrane seems not to be affected by TTO since no leakage of the Mycoplasma cell was observed after oil treatment. In the HET-CAM test TTO did not show any visible signs of irritation in concentrations less than 25%. Although the active component in TTO that has anti-mycoplasmal activity is not known, it seems very promising to use TTO tentatively for mouth washing and inhalation in case of Mycoplasma-pneumoniae-infection.

Comparative study on the in vitro antibacterial activity of Australian tea tree oil, cajuput oil, niaouli oil, manuka oil, kanuka oil, and eucalyptus oil.

To compare the antibacterial activity of the Australian tea tree oil (TTO) with various other medicinally and commercially important essential myrtaceous oils (cajuput oil, niaouli oil, kanuka oil, manuka oil, and eucalyptus oil) the essential oils were first analysed by GC-MS and then tested against various bacteria using a broth microdilution method. The highest activity was obtained by TTO, with MIC values of 0.25% for Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella choleraesuis, Shigella flexneri, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, S. saprophyticus, and S. xylosus. It is noteworthy that manuka oil exhibited a higher activity than TTO against gram-positive bacteria, with MIC values of 0.12%. Both TTO and manuka oil also demonstrated a very good antimicrobial efficacy against various antibiotic-resistant Staphylococcus species. Pseudomonas aeruginosa was resistant to all essential oils tested, even at the highest concentration of 4%.

Degradation products of monoterpenes are the sensitizing agents in tea tree oil.

BACKGROUND: Patients using tea tree oil (TTO) topically may become sensitized to this natural remedy. More than 30 cases have been documented in the literature since 1991. OBJECTIVE: Freshly distilled, as well as oxidized TTO, some fractions, and single constituents were used for experimental sensitization in guinea pigs. TTO was stored on a window sill to study the influence of light, oxygen, and warmth. The oxidized oil and different fractions were devoted to experimental sensitization in guinea pigs to determine their sensitizing potency. Fifteen constituents were patch tested in TTO-sensitive patients to find how many may play a role as contact allergens. METHODS: Guinea pigs were sensitized by a modified FCA-method (Freund's complete adjuvant) with freshly distilled TTO, oxidized TTO, the monoterpene and sesquiterpene fraction, and 1, 8-cineole. TTO-sensitive patients were tested with 15 typical constituents and degradation products. Gas chromatographic analysis was used to detect degradation products of the deteriorated TTO. RESULTS: Fresh TTO was revealed to be a very weak sensitizing material whereas oxidized TTO was 3 times stronger. The monoterpene fraction showed to be a stronger sensitizer than the sesquiterpene fraction. All 11 patients reacted mostly with a ++-plus or even a -plus reaction to alpha-terpinene, terpinolene and ascaridol. alpha-Phellandrene became positive in four patients, myrcene in only two. Gas chromatographic analyses showed that the formation of peroxides increased within 4 days from less than 50 to more than 500 ppm. Peroxides, epoxides and endoperoxides were formed. Deterioration products of alpha-terpinene were found to be mainly p-cymene, ascaridol, isoascaridol, a ketoperoxide, and colorless crystals that likely were 1,2,4-trihydroxy menthane. The p-cymene content increased dramatically from 2% to 11.5%. alpha- and gamma-terpinene, as well as terpinolene, were reduced to one half of their former concentration. Ascaridol and isoascaridol have never before been found in TTO. CONCLUSION: Tea tree oil kept in open and closed bottles or other containers undergoes photooxidation within a few days to several months, leading to the creation of degradation products that are moderate to strong sensitizers. Peroxides, epoxides and endoperoxides, like ascaridol and 1,2,4-trihydroxy menthane, are formed. These must be considered responsible for the development of allergic contact dermatitis seen in individuals treating themselves with the oil. A test series with 15 characteristic constituents is recommended for patch testing.

In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal angiogenesis.

PURPOSE: Numerous investigations have stressed the significance of leukocytes in early angiogenesis. Leukocytes invade the cornea, and the location of their extravasation corresponds to the site of vessel ingrowth. The interactions between leukocytes and vascular endothelium are mediated by various proteins, including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated in vivo. METHODS: Corneal neovascularization was induced in New Zealand White rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS: Limbal vessels showed increased leukocyte adhesion 24 hours after pellet implantation: The number of rolling and sticking leukocytes was significantly increased compared with the number in control animals (P < 0.01). Treatment with anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in early angiogenesis. This model may serve for investigation of the significance of adhesion molecules by in vivo observation and quantification.

Pharmaceutical and medicinal aspects of Australian tea tree oil.

The essential tea tree oil has been widely used in modern medicine and cosmetics in recent years. Although there are clinical data to show the benefical effects (e.g. antiseptic, antimicrobial, antioxidative) of this oil, dose-response studies are lacking. This paper reviews the clinical use of this essential oil, especially as a topical application.