Clinical and Mycological Evaluation of Therapeutic Effectiveness of Solanum chrysotrichum Standardized Extract on Patients with Pityriasis capitis (Dandruff). A Double Blind and Randomized Clinical Trial Controlled with Ketoconazole

• Abstract
• Introduction
• Material and Methods
• Plant material and extract preparation
• HPLC analysis
• Calibration curves
• Subjects
• Inclusion criteria
• Non-inclusion criteria
• Experimental procedure
• Mycological studies
• Outcome variables
• Statistical analysis
• Results
• Discussion
• Acknowledgements
• References

Abstract

Dandruff (also called Pityriasis capitis) is a seborrhoeic dermatitis of the scalp. It has been correlated with the pathological colonization of the scalp with yeast from the genus Malassezia; this illness has a worldwide distribution and represents 25 % of all scalp dermatosis cases. It has been demonstrated that the extract obtained from leaves of the plant Solanum chrysotrichum possesses biological activity against dermatophytes and yeast. Different steroidal saponins with antimycotic activity have been isolated from the active extract. Clinical trials with standardized extracts prepared with this vegetal species report high rates of clinical and mycological effectiveness in the treatment of Tinea pedis, without producing secondary effects. The aim of this randomized, double blind and controlled clinical study, was to compare the therapeutic effectiveness and tolerability of a shampoo containing a standardized extract of S. chrysotrichum (applied every third day, for 4 weeks), against 2 % ketoconazole in the topical treatment of Pityriasis capitis. From a total of 120 patients with the clinical diagnosis of Pityriasis capitis, 14 subjects were eliminated because the presence of Malassezia was not proved, another two patients withdrew from the study due to non-medical causes and one more withdrew because Tinea capitis was diagnosed. Therefore, the final analysis included 51 subjects in the experimental group and 52 in the control; in 45.6 % of the cases M. furfur was identified as the pathogenic agent, in 44.66 % M. globosa was isolated, and 9.71 % of the patients had a mixed infestation. At the end of the treatment period, the prepared phytopharmaceutical with the standardized extract from S. chrysotrichum achieved a clinical effectiveness (total absence of signs and symptoms produced by Pityriasis capitis) of 92.16 %; the mycological effectiveness (absence of Malassezia spp. in the direct examination and culture) was 68.63 %; whilst the tolerability (absence of side effects that prompt subjects to abandon the treatment) was 100 %. The therapeutic success (clinical and mycological effectiveness plus tolerability) was 64.71 %. The comparison of these results with that obtained from the group treated with 2 % ketoconazole, showed no significant differences (χ², p > 0.23). These results show the therapeutic effectiveness and tolerability of the standardized extract from S. chrysotrichum on the local treatment of Pityriasis capitis associated with the yeast of the genus Malassezia.

Introduction

Pityriasis capitis has been a known illness since ancient times [1], it has a cosmopolitan distribution, with high frequencies in America and Europe, and represents 6 % of dermatological attention. This disease represents almost 25 % of scalp dermatosis cases, and predominates amongst male patients between 30 and 49 years old; in AIDS patients it is present in almost 80 % of cases [2]. Pityriasis capitis is a pathology that prevails in poor socioeconomic levels with bad sanitary conditions [3]. Among associated physio-pathological factors, we can find a decrease of intracellular lipids, alteration of the barrier function, and the colonization by different yeast-form agents from the Malassezia genus [4], [5]. Recently, the yeast infections that usually had a good resolution under treatment with azoles have become resistant to antibiotics, especially on inmunosuppressed patients in whom resistance reaches 34 %. For this reason, it is necessary to assay new therapeutic alternatives [6].

The plant species Solanum chrysotrichum is widely used in Mexican Traditional Medicine of the Highlands of Chiapas as a remedy for the treatment of ”athlete’s foot”. Previous pharmacological studies have demonstrated the antimycotic in vitro effect of the leaves from S. chrysotrichum against Trichophyton mentagrophytes, T. rubrum, Microsporum gypseum and Candida albicans [7], [8], while controlled clinical trials verified the effectiveness of this plant for treating Tinea pedis with high rates of clinical and mycological effectiveness without producing side effects [9].

Different phytochemical and microbiological studies have reported the isolation, structure identification, and quantification of some spirostanic saponins, which have different degrees of antimycotic activity: (6α-O-β-D-xylopyranosyl-(1→3)-β-D-quinovopyranosyl-(25R)-5α-spirostan-3β-ol (SC-2), 6α-O-β-D-xylopyranosyl-(25R)-5α-spirostan-3β-ol (SC-3), 6α-O-β-D-quinovopyranosyl-(25R)-5α-spirostan-3β-ol (SC-4), 6-α-O-α-L-rhamnopyranosyl-(1→3)-β-D-quinovopyranosyl-(25R)-5α-spirostan-3β-ol (SC-5) and 6α-O-α-L-rhamnopyranosyl-(1→3)-β-D-quinovopyranosyl-(25R)-5α-spirostan-3β, 23α-diol (SC-6), with SC-2 being the most active [10], [11]. The aim of the present study was to compare the clinical and mycological effectiveness, as well as the tolerability of a phytopharmaceutical prepared as shampoo with 12.5 % of a S. chrysotrichum extract (standardized on the spirostanic saponins content), with 2 % ketoconazole, also formulated as shampoo, on the topical treatment of Pityriasis capitis associated with the infection of yeast from the Malassezia genus.

Material and Methods

Plant material and extract preparation

Solanum chrysotrichum Schldh. (Solanaceae) leaves were collected from a controlled crop in the town of Xochitepec, in the State of Morelos, Mexico. Voucher samples were prepared and stored for reference at the IMSSM herbarium under the code 13 082 and 13 083. The collected plant material, once dry (11.4 kg), was extracted by maceration with n-hexane and subsequently with methanol for 24 h at room temperature (35 L, three times each). The n-hexane extract was discarded and the methanol extract (1403 g, 12.3 %) was decolored on activated charcoal (Merck) using methanol as eluent and obtaining a yield of 1194 g (10.47 %). Finally, the product was evaporated to dryness in a rotary evaporator under reduced pressure and stored at -20 °C until it was prepared for pharmaceutical presentation. The chromatographic analysis of this extract (see below) determined the concentration of the antimycotic steroidal saponins as follows: SC-2, 6.50 mg/g; SC-3, 2.49 mg/g; SC-4, 4.58 mg/g; SC-5, 7.50 mg/g and SC-6, 31.42 mg/g. Total content of the antimycotic saponins was 52.49 mg/g (0.524 %). For the experimental treatment, plastic containers were prepared with a 60 g mixture of neuter shampoo and the dry S. chrysotrichum extract (12.5 %). Similarly, an identical control treatment was also prepared, which contained a 60 g mixture prepared with neuter shampoo and ketoconazole (2 %). With the aim to blind the experimental procedure, in this case, an inert pigment was added in order to produce a coloring similar to that of the experimental treatment.

Both treatments, in 60 mL plastic containers, were identified as treatment 1 and 2.

HPLC analysis

The antimycotic saponins fraction was obtained by fractionation of 0.5 g of ethyl acetate extract on a silica gel solid-phase extraction tube of 6 mL (Supelclean LC-Si, Supelco), and eluted with 15 mL of methanol. The obtained extract was analyzed on a Merck Hitachi HPLC system with, AS-2000A autosampler, L-6200A intelligent pump system controller (DAD System Manager software) and a R1 - 71 refraction index detector, using a purosphere® RP-18 (5 μm) column 125 × 4 mm (Merck) at 25 °C.

Saponins SC-2, SC-3 and SC-4 were analyzed with a mobile phase consisting of one solvent mixture of acetonitrile/water (55 : 45, v/v) with a flow rate of 1.2 mL/min. Saponins SC-5 and SC-6 were analyzed with an isocratic mobile phase of acetonitrile/water (33 : 67, v/v) with a flow rate of 1.5 mL/ min. The injection volume was 70 μL. The retention times of these compounds were as follows: SC-2, 4.90 min; SC-3, 4.01 min; SC-4, 5.4 min; SC-5, 4.78 min and SC-6, 5.7 min.

Calibration curves

Standard solutions were prepared with every compound: SC-2, SC-3, SC-4, SC-5 and SC-6 previously isolated from the wild plant [11]. Calibration curves were constructed with dilutions of 100, 200, 400 and 800 μg/mL in methanol. A volume of 70 μL was injected and calibration curves were based on peak areas of the HPLC chromatograms. The calibration curves showed an R² of 0.991 for SC-2 to SC-4 and R² of 0.996 for SC-5 to SC-6.

Subjects

The study was carried out on outpatients from the primary health care service of the ”Hospital General Regional No. 1” of the Mexican Institute of Social Security (IMSS) in Cuernavaca, Morelos. With institutional ethic committee approval, a total of 120 patients clinically diagnosed with Pityriasis capitis were included. All patients were informed about the project and have signed consent forms for participation in this clinical investigation. Afterwards, they were randomized to one of the two treatments.

Inclusion criteria

Subjects were of both sexes, between 15 and 45 years of age, and affiliated with IMSS. They had to be resident in Cuernavaca City or in the outskirts, with a clinical diagnosis of Pityriasis capitis, without treatment for this illness during the last month, and with a positive mycological direct test confirming the presence of yeast from the Malassezia genus on the scalp.

Non-inclusion criteria

Pregnant women, women who were breast-feeding, patients who had Pityriasis capitis complicated with another bacterial or mycological infection of the scalp, and subjects with known intolerance to some of the azole compounds or to the species under study.

Experimental procedure

The study was conducted over 4 weeks and consisted of applying the assigned treatment in the form of shampoo directly on the dampened scalp, then rubbing until obtaining abundant lather, letting the shampoo act for 5 minutes, and then rinsing with clean water. This procedure was repeated every third day for 4 continuous weeks. At the beginning of the study, every patient received a 60 mL plastic container with the assigned treatment and written instructions of how to use it. Subsequently, all patients were evaluated two times more, in order to ascertain the outcome variables and the treatment adherence. The first evaluation was carried out two weeks after the treatment began, and the patients received a fresh treatment by changing the empty container for a new one. The last evaluation took place 4 weeks after the first day of treatment. During the period of study, at the beginning and after two and four weeks of treatment, mycological tests were done, and consisted of a direct examination with potassium hydroxide and the culture of scaly and hair obtained from the affected area of the head.

The clinical evaluation consisted of a record that included a scale of 5 severity degrees (0 = absent, 1 = slight, 2 = moderate, 3 = intense, 4 = severe) of signs and symptoms detected (scaling, dandruff flakes, scabs, active border, erythema, pustules, itching and local pain). All patients had to give back the utilized containers in order to evaluate treatment adherence.

Mycological studies

Direct examination. Scales and hair, including the hair bulb, were obtained in duplicate from the most affected area of the head, and fixed with a clear adhesive film on a glass slip. The samples were stained with the Albert colorant in order to identify the yeast form elements and their microscopic morphology thus establishing the species of Malassezia involved (M. furfur: oval, cylindrical or bottle forms; M globosa: spherical forms) [12]. The evaluation was qualitative and depended on the amount of detected elements. Results were declared: 0 = absent, (+) = scarce, (++) = moderate, (+++) = abundant, (++++) = excessive. In those cases, after two and four weeks treatment, in which no scales were found, only the hair and hair bulbs were analyzed. The two species of Malassezia detected in our study were M. furfur and M globosa.

Cultures. Scales and the proximal portion of hair were spread on mycobiotic agar plus olive oil and incubated for 15 days at 25 °C. It was declared a negative culture when, at the end of the incubation period, no colonies were detected. It was declared a positive culture, when white or yellow colonies of creamy consistency were detected, showing the presence of yeast or yeast form elements with the Gram stain. The Malassezia species were identified by biochemical tests [13].

Outcome variables

The evaluated outcome variables were: a) Clinical effectiveness, which was declared when the signs and symptoms attributed to the pathology under study and that were detected at basal conditions, were totally absent; b) Mycological effectiveness, which was achieved upon detection of a negative direct examination and culture; c) Tolerability, which was determined by the absence of local and systemic side effects attributed to the assigned treatment; d) Therapeutic successes, when there was clinical and mycological effectiveness, as well as tolerability. A therapeutic failure was declared when, at the end of the treatment, there were signs and symptoms of the pathology under study, or a positive mycological test, as well as when the patient showed severe or intense side effects, in which case it was necessary to withdraw the treatment.

Statistical analysis

The obtained results were captured in a data base and analyzed with the STATA statistical software. In order to identify significant differences between categorical variables, the χ² hypothesis test was employed; for continuous variables, with normal distribution, the ANOVA test was used; whilst the Mann-Whitney test was used for identifying differences between medians. Values of p ≤ 0.05 were considered for establishing significant differences.

Results

A total of 120 patients with a clinical diagnosis of Pityriasis capitis were included, 14 of whom were eliminated because the initial mycological direct examination detected no yeast presence; therefore, the basal conditions evaluated 106 subjects. During the first two weeks, two patients withdrew from the study due to non-medical reasons and one more was eliminated because a clinical pattern of Tinea capitis was detected. The final analysis included 103 patients, 51 in the experimental group and 52 in the control. Table [1] shows the basal conditions of the population under study. It is notable that, in a statistical analysis of the evaluated parameters, no significant differences between groups of treatment were found (p > 0.14). After analyzing the entire studied population, it was found that the average age was 34.8 years, the mean time evolution of the disease was 17.9 months; 26 subjects (24.27 %) had previously received empirical treatments (cosmetic products for local application as shampoo) for treating dandruff. In this study women predominated (71, 68.93 %), half of the patients had a relative with dandruff; a moderate degree of severity was present in 56 subjects (54.37 %), while in 44 subjects (42.72 %), an excessive amount of yeast forms were detected. Malassezia furfur and M. globosa, in a similar proportion, were the two types of yeast identified, and 10 cases (9.71 %) showed a mixed infestation. Only 8 subjects had a positive culture (7.77 %), four in the S. chrysotrichum group (2 of M. globosa, 1 of M. furfur and the other with a mixed infestation) and four in ketoconazole group (all with M. furfur).

Clinical improvement, after two and four weeks treatment, did not present differences between both evaluated groups (Table [2]). At the end of the second week of treatment, no severe cases persisted, and the majority of the subjects had only slight cases. At the end of four weeks of treatment, by clinical observation, 47 patients (92.16 %) from the S. chrysotrichum group and 45 from ketoconazole (86.54 %) showed improvement. In total, at the end of the treatment, clinically 92 patients (89.32 %) had been restored to health.

During the study period, which included three mycological evaluations, no significant differences between treatments were detected on direct examination. On basal conditions, the majority of cases presented abundant and excessive amounts of yeast. It is interesting to mention that at the end of two weeks of treatment, the majority of the cases achieved a negative direct mycological examination (Table [3]).

As shown in Table [4], after two and four weeks treatment, the rates of clinical effectiveness (total absence of signs and symptoms) did not show significant differences between the groups under study (p > 0.30).

In Table [5], it is important to observe that after two weeks of treatment, the percentage of mycological effectiveness (negative direct examination) was higher (20 percentage points) in the group treated with ketoconazole, reaching significant differences (p < 0.05). Nevertheless, at the end of the treatment this difference was reduced to 10 %, without reaching statistical difference between groups (p > 0.23).

At the end of the two and four weeks of treatment, the rates of therapeutic effectiveness (clinical effectiveness plus mycological effectiveness), did not show statistical differences between the two groups (p > 0.14) (Table [6]).

On the other hand, both treatments were satisfactorily tolerated, without presenting any side effects; therefore, the tolerability percentages (absence of side effects in which it was necessary to withdraw the treatment) were 100 % for both treatments. Finally, given the 100 % tolerability ratings in both, the therapeutic success value (therapeutic effectiveness plus tolerability), was identical to that of the therapeutic effectiveness.

Discussion

The presence of yeast from the Malassezia genus, specially M. furfur (also known as M. ovalis and Pityrosporum ovale), is involved in the etiology of Pityriasis capitis [14]. Local treatment has been established based on the topical application of different antimycotic agents such as zinc pyrithione, selenium sulfide, ciclopirox olamine plus salicylic acid and ketoconazole at different concentrations for four weeks [15]. Ketoconazole is the product that has demonstrated the best in vitro activity against Pityrosporum orbiculare, with concentrations around 0.02 μg/mL [16], as well as the highest rates of clinical and mycological effectiveness, and the lowest rates of relapses in the treatment of Pityiriasis capitis [17]. Previous studies have also clearly established the use of ketoconazole as a prophylactic and for the treatment of patients suffering from Pityriasis capitis, reporting a complete improvement in from 73 % to 88 % of cases [15], [18]. The anti-inflammatory activity of this drug has also been reported, which provides an extra therapeutic effect [19]. On the other hand, some compounds obtained from plants have been used for the treatment of Pityriasis capitis, reaching rates of effectiveness lower than 50 % [20].

Since the aim of our study was to evaluate the clinical and mycological effectiveness of S. chrysotrichum in the treatment of Pityriasis capitis, we decided not to include subjects with negative mycological test results (direct examination and culture). Lower rates of positive cultures were evident in our study, as the isolation of the pathogenic agent was only possible in 8 cases (7.76 %). Probably, that was due to the normal difficulties of cultivating yeasts from the Malassezia genus, as has already been reported by other authors [21]. For that reason, in order to achieve the identification of the Malassezia species involved, we decided to evaluate the microscopic morphology of yeasts in a direct examination; consequently, this test was used for evaluating mycological effectiveness.

It must be noted that all the parameters evaluated on basal conditions showed no differences between the two groups of treatment (p > 0.14). It was interesting to find that half of the subjects under study had relatives suffering from the same pathology, which confirms the high contagiousness of this disease and the possibility of relapse. The predominating clinical pattern was catalogued as moderate. In this study women predominated in a ratio of 2 : 1, and the average age was 34.8 years, the evolution time of dandruff was 17.9 months, while a quarter of the subjects have already received, without success, empirical cosmetic treatments for the management of dandruff. All these data agree with others reported in the scientific literature.

Previous studies have shown the antifungal activity of S. chrysotrichum. In vitro studies have demonstrated its activity against yeasts and dermatophytes, while, on two clinical trials this plant species has shown to have effectiveness and safety in the treatment of Tinea pedis [9], [10]. The present study shows that the S. chrysotrichum extract is effective and safe for treating Pityriasis capitis associated with yeast from the Malassezia genus. That implies that our extract possesses a wide spectrum of antimycotic activity, because it was able to eradicate the yeasts as well as the dermatophytes. This contrasts with other antimycotic compounds with a reduced spectrum, such as terbinafine and nystatine which are specific against dermatophytes, and yeast, respectively.

The S. chrysotrichum extract used in the present clinical trial was different to that used in the previous clinical study on patients with Tinea pedis. In this case, the extract was decolored by activated charcoal, thus avoiding the pigmentation of the treated area. On the other hand, this extract was a rich fraction of antimycotic saponins; the total concentration of saponins was 52.49 mg/g of extract (656 mg/100 g of shampoo; the final concentration was 0.65 %).

The control group was treated with ketoconazole, which is the most effective imidazole against M. furfur (one of the pathogenic agents identified in this study) [22]. In spite of that, the standardized extract from S. chrysotrichum showed a rate of antimycotic effectiveness that did not differ significantly from that obtained with 2 % ketoconazole. Finally, based on the results of this study, it is possible to conclude that the extract from the Solanum chrysotrichum leaves (formulated as shampoo), standardized in the antimycotic spirostan saponins, is effective in the local treatment of Pityriasis capitis associated with yeast from the Malassezia genus.

Acknowledgements

The authors are grateful to Dr. Corinne Hayden for critically reviewing the manuscript.

References

• 1 Saint-Leger D. The history of dandruff and dandruff in history. A homage to Raymond Sabouraud.  Ann Dermatol Venereol. 1990;  117 23-7
  PubMedSearch in Google Scholar
• 2 Fitz-Patrich E. Dermatología en Medicina Familiar 3a. Ed. Editorial Panamericana México; 1995: 380-2
  Search in Google Scholar
• 3 Inanir I, Sahin M T, Gunduz K, Dinc G, Turel A, Ozturkcan S. Prevalence of skin conditions in primary school children in Turkey: differences based on socioeconomic factors.  Pediatr Dermatol. 2002;  19 307-11
  CrossrefPubMedSearch in Google Scholar
• 4 Harding C R, Moore A E, Rogers J S, Meldrum H, Scott A E, McGlone F P. Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.  Arch Dermatol Res. 2002;  294 221-30
  PubMedSearch in Google Scholar
• 5 Schmidt A. Malassezia furfur: a fungus belonging to the physiological skin flora and its relevance in skin disorders.  Cutis. 1997;  59 21-4
  PubMedSearch in Google Scholar
• 6 Rodero L, Boutureira M, Demkura H, Burkett A, Fernandez C, Losso M, Jauregui-Rueda H, Monticelli A, Vitale R, Canteros C, Hochenfellner F, Vivot W, Davel G. Yeast infections: causative agents and their antifungal resistance in hospitalized pediatric patients and HIV-positive adults.  Rev Argent Microbiol. 1997;  29 7-15
  PubMedSearch in Google Scholar
• 7 Lozoya X, Aguilar A. Encuesta sobre el uso actual de plantas en la medicina tradicional Mexicana.  Rev Med IMSS. 1987;  25 283-91
  PubMedSearch in Google Scholar
• 8 Lozoya X, Navarro V, García M, Zurita M. Solanum chrysotrichum (Schldl.) a plant used in Mexico for the treatment of skin mycoses.  J Ethnopharmacol. 1991;  36 127-32
  PubMedSearch in Google Scholar
• 9 Herrera-Arellano A, Rodríguez-Soberanes A, Martínez-Rivera MA; Martínez-Cruz E, Zamilpa A, Alvarez L, Tortoriello J. Effectiveness and tolerability of a standardized phytodrug derived from Solanum chrysotrichum on tinea pedis. A controlled and randomized clinical trial.  Planta Med. 2003;  69 390-5
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Alvarez L, Pérez M C, González J L, Navarro V, Villareal M L, Olson J O. SC-1 an antimycotic spirostan saponin from S. chrysotrichum .  Planta Med. 2001;  67 372-4
  Thieme ConnectPubMedSearch in Google Scholar
• 11 Zamilpa A, Tortoriello J, Navarro V, Delgado G, Alvarez L. Five new steroidal saponins from S. chrysotrichum leaves and their antimycotic activity.  J Nat Prod. 2002;  65 1815-19
  CrossrefPubMedSearch in Google Scholar
• 12 Conti Diaz I A, Civila E, Veiga R. The importance of microscopic examination in the management of desquamative diseases of the scalp.  Mycopathologia.. 2002;  153 71-5
  CrossrefPubMedSearch in Google Scholar
• 13 Nakabayashi A, Sei Y, Guillot J. Identification of Malassezia species isolated from patients with seborrhoeic dermatitis, atopic dermatitis, pityriasis versicolor and normal subjects.  Med Mycol. 2000;  38 337-41
  PubMedSearch in Google Scholar
• 14 Arrese J E, Piérard-Franchimont C, De Doncker P, Heremans A, Cauwenbergh G, Piérard G E. Effect of ketoconazole-medicated shampoos on squamometry and Malassezia ovalis load in Pityriasis capitis .  Cutis. 1996;  58 235-7
  PubMedSearch in Google Scholar
• 15 Squire R A, Goode K. A randomized, single-blind, single-centre clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5 %) and salicylic acid (3 %), or ketoconazole (2 %, Nizoral) for the treatment of dandruff/seborrhoeic dermatitis.  J Dermatolog Treat. 2002;  13 51-60
  CrossrefPubMedSearch in Google Scholar
• 16 Van Cutsem J, Van Gerven F, Fransen J, Schrooten P, Janssen P AJ. The in vitro antifungal activity of ketoconazole, zinc pyrithione, and selenium sulphide against pityrosporosis and their efficacy as a shampoo in the treatment of experimental Pityrosporum in guinea pigs.  J Am Acad Dermatol. 1990;  2 933-8
  PubMedSearch in Google Scholar
• 17 Pierard-Franchimont C, Goffin V, Decroix J, Pierard G E. A multicenter randomized trial of ketoconazole 2 % and zinc pyrithione 1 % shampoos in severe dandruff and seborrheic dermatitis.  Skin Pharmacol Appl Skin Physiol. 2002;  15 434-41
  CrossrefPubMedSearch in Google Scholar
• 18 Maddin W S, Margesson L J, Rosenthal D. A randomized, double-blind trial of ketoconazole 2 % shampoo versus selenium sulfide 2.5 % shampoo in the treatment of moderate to severe dandruff.  J Am Acad Dermatol. 1993;  29 1008-12
  PubMedSearch in Google Scholar
• 19 Yoshimura T, Kudoh K, Aiba S, Tagami H. Anti-inflammatory effects of ketoconazole for the inflammation induced on the skin of hairless guinea-pigs by repeated applications of heat-killed spores of M. furfur: A comparative study with hydrocortisone 17-butyrate.  J Dermatol Treat. 1995;  6 113-6
  PubMedSearch in Google Scholar
• 20 Satchell A C, Saurajen A, Bell C, Barnetson R S. Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of dandruff with 5 % tea tree oil shampoo.  J Am Acad Dermatol. 2002;  47 852-5
  CrossrefPubMedSearch in Google Scholar
• 21 Kwon-Chung K J, Bennett J E. Medical mycology. Lea and Febiger Philadelphia; 1992: pp 81-102
  Search in Google Scholar
• 22 Van Gerven F, Odds F C. The anti-Malassezia furfur activity in vitro and in experimental dermatitis of six imidazole antifungal agents: bifonazole, clotrimazole, flutrimazole, ketoconazole, miconazole and sertaconazole Mycoses. 1995 38: 389-93
  Search in Google Scholar

Dr. A. Herrera-Arellano

Centro de Investigación Biomédica del Sur

IMSS

Argentina 1 Xochitepec

Mor

México 62790

Phone: +52-777-3612-155

Fax: +52-777-3612-194

Email: armandoha_mx@yahoo.com.mx

References

• 1 Saint-Leger D. The history of dandruff and dandruff in history. A homage to Raymond Sabouraud.  Ann Dermatol Venereol. 1990;  117 23-7
  PubMedSearch in Google Scholar
• 2 Fitz-Patrich E. Dermatología en Medicina Familiar 3a. Ed. Editorial Panamericana México; 1995: 380-2
  Search in Google Scholar
• 3 Inanir I, Sahin M T, Gunduz K, Dinc G, Turel A, Ozturkcan S. Prevalence of skin conditions in primary school children in Turkey: differences based on socioeconomic factors.  Pediatr Dermatol. 2002;  19 307-11
  CrossrefPubMedSearch in Google Scholar
• 4 Harding C R, Moore A E, Rogers J S, Meldrum H, Scott A E, McGlone F P. Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.  Arch Dermatol Res. 2002;  294 221-30
  PubMedSearch in Google Scholar
• 5 Schmidt A. Malassezia furfur: a fungus belonging to the physiological skin flora and its relevance in skin disorders.  Cutis. 1997;  59 21-4
  PubMedSearch in Google Scholar
• 6 Rodero L, Boutureira M, Demkura H, Burkett A, Fernandez C, Losso M, Jauregui-Rueda H, Monticelli A, Vitale R, Canteros C, Hochenfellner F, Vivot W, Davel G. Yeast infections: causative agents and their antifungal resistance in hospitalized pediatric patients and HIV-positive adults.  Rev Argent Microbiol. 1997;  29 7-15
  PubMedSearch in Google Scholar
• 7 Lozoya X, Aguilar A. Encuesta sobre el uso actual de plantas en la medicina tradicional Mexicana.  Rev Med IMSS. 1987;  25 283-91
  PubMedSearch in Google Scholar
• 8 Lozoya X, Navarro V, García M, Zurita M. Solanum chrysotrichum (Schldl.) a plant used in Mexico for the treatment of skin mycoses.  J Ethnopharmacol. 1991;  36 127-32
  PubMedSearch in Google Scholar
• 9 Herrera-Arellano A, Rodríguez-Soberanes A, Martínez-Rivera MA; Martínez-Cruz E, Zamilpa A, Alvarez L, Tortoriello J. Effectiveness and tolerability of a standardized phytodrug derived from Solanum chrysotrichum on tinea pedis. A controlled and randomized clinical trial.  Planta Med. 2003;  69 390-5
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Alvarez L, Pérez M C, González J L, Navarro V, Villareal M L, Olson J O. SC-1 an antimycotic spirostan saponin from S. chrysotrichum .  Planta Med. 2001;  67 372-4
  Thieme ConnectPubMedSearch in Google Scholar
• 11 Zamilpa A, Tortoriello J, Navarro V, Delgado G, Alvarez L. Five new steroidal saponins from S. chrysotrichum leaves and their antimycotic activity.  J Nat Prod. 2002;  65 1815-19
  CrossrefPubMedSearch in Google Scholar
• 12 Conti Diaz I A, Civila E, Veiga R. The importance of microscopic examination in the management of desquamative diseases of the scalp.  Mycopathologia.. 2002;  153 71-5
  CrossrefPubMedSearch in Google Scholar
• 13 Nakabayashi A, Sei Y, Guillot J. Identification of Malassezia species isolated from patients with seborrhoeic dermatitis, atopic dermatitis, pityriasis versicolor and normal subjects.  Med Mycol. 2000;  38 337-41
  PubMedSearch in Google Scholar
• 14 Arrese J E, Piérard-Franchimont C, De Doncker P, Heremans A, Cauwenbergh G, Piérard G E. Effect of ketoconazole-medicated shampoos on squamometry and Malassezia ovalis load in Pityriasis capitis .  Cutis. 1996;  58 235-7
  PubMedSearch in Google Scholar
• 15 Squire R A, Goode K. A randomized, single-blind, single-centre clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5 %) and salicylic acid (3 %), or ketoconazole (2 %, Nizoral) for the treatment of dandruff/seborrhoeic dermatitis.  J Dermatolog Treat. 2002;  13 51-60
  CrossrefPubMedSearch in Google Scholar
• 16 Van Cutsem J, Van Gerven F, Fransen J, Schrooten P, Janssen P AJ. The in vitro antifungal activity of ketoconazole, zinc pyrithione, and selenium sulphide against pityrosporosis and their efficacy as a shampoo in the treatment of experimental Pityrosporum in guinea pigs.  J Am Acad Dermatol. 1990;  2 933-8
  PubMedSearch in Google Scholar
• 17 Pierard-Franchimont C, Goffin V, Decroix J, Pierard G E. A multicenter randomized trial of ketoconazole 2 % and zinc pyrithione 1 % shampoos in severe dandruff and seborrheic dermatitis.  Skin Pharmacol Appl Skin Physiol. 2002;  15 434-41
  CrossrefPubMedSearch in Google Scholar
• 18 Maddin W S, Margesson L J, Rosenthal D. A randomized, double-blind trial of ketoconazole 2 % shampoo versus selenium sulfide 2.5 % shampoo in the treatment of moderate to severe dandruff.  J Am Acad Dermatol. 1993;  29 1008-12
  PubMedSearch in Google Scholar
• 19 Yoshimura T, Kudoh K, Aiba S, Tagami H. Anti-inflammatory effects of ketoconazole for the inflammation induced on the skin of hairless guinea-pigs by repeated applications of heat-killed spores of M. furfur: A comparative study with hydrocortisone 17-butyrate.  J Dermatol Treat. 1995;  6 113-6
  PubMedSearch in Google Scholar
• 20 Satchell A C, Saurajen A, Bell C, Barnetson R S. Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of dandruff with 5 % tea tree oil shampoo.  J Am Acad Dermatol. 2002;  47 852-5
  CrossrefPubMedSearch in Google Scholar
• 21 Kwon-Chung K J, Bennett J E. Medical mycology. Lea and Febiger Philadelphia; 1992: pp 81-102
  Search in Google Scholar
• 22 Van Gerven F, Odds F C. The anti-Malassezia furfur activity in vitro and in experimental dermatitis of six imidazole antifungal agents: bifonazole, clotrimazole, flutrimazole, ketoconazole, miconazole and sertaconazole Mycoses. 1995 38: 389-93
  Search in Google Scholar

Dr. A. Herrera-Arellano

Centro de Investigación Biomédica del Sur

IMSS

Argentina 1 Xochitepec

Mor

México 62790

Phone: +52-777-3612-155

Fax: +52-777-3612-194

Email: armandoha_mx@yahoo.com.mx