References Antifungal activity of 33% grapefruit

486 Letter
References
factors for hypertrophic scars.4 Ozluer et al. reported four renal
transplant patients who developed plantar hypertrophic scars
following carbon dioxide laser ablation of recalcitrant plantar
warts.5 Our patient was a pregnant woman suffering from
a plantar hypertrophic scar. The exact pathogenesis of the
plantar hypertrophic scars remains unknown. In our case, the
suturing tension caused by the excision of a large wart seems
to be the major factor for hypertrophic scar formation. In
addition, pregnancy might also speed up hypertrophic scar
formation in our patient. Jacobsson reported a case, whose
scar became hypertrophic during pregnancy.6 Geschichter and
Lewis reported that keloid tissue contained high amounts
of oestrogen.7 Estrogens show their effect by altering the polymerization of acid mucopolysaccharides and change the properties of ground substance with increased hygroscopic effects.8
Many treatment modalities were reported in the treatment of
plantar keloids and hypertrophic scars without succes. However, some authors state that excision, postoperative electron
beam therapy and secondary intension healing provide a useful
approach in the management of plantar keloids. Radiotherapy
may usually combine with other therapeutic options such as
intralesional corticosteroid injections and tangential surgical
excision of the lesion.9 We did not perform any aggressive treatment for the plantar hypertrophic scar in our patient as she was
pregnant and any invasive treatment could lead to an additional
hypertrophic scar formation.
In conclusion, plantar areas are unusual regions for hypertrophic
scar formation. Plantar hypertrophic scars are rare but important
alterations that may lower the quality of life of the patient.
According to the literature’s data and our experience, we think
that maternal oestrogens might be additional factors to provocate
plantar hypertrophic scar proliferation in our patient, whereas
further studies are needed for the elucidation of the exact pathogenesis of the plantar hypertrophic scar formation in pregnancy.
1 English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol
Surg 1999; 25: 631–638.
2 Berman B, Flores F. Recurrence rates of excised keloids treated
with postoperative triamcinolone acetonide injections or interferon
alfa-2b injections. J Am Acad Dermatol 1997; 37: 755–757.
3 Aslan G, Terzioglu A, Cigsar B. A massive plantar keloid. Ann Plast
Surg 2001; 47: 581.
4 Brissett AE, Sherris DA. Scar contractures, hypertrophic scars, and
keloids. Facial Plast Surg 2001; 17: 263–272.
5 Ozluer SM, Chuen BY, Barlow RJ, Markey AC. Hypertrophic scar
formation following carbon dioxide laser ablation of plantar warts
in cyclosporin-treated patients. Br J Dermatol 2001; 145: 1005 –1007.
6 Jacobsson F. The treatment of keloids at radium hemmet, 1921–
1941. Acta Radiol 1948; 29: 251.
7 Geschichter CF, Lewis D. Tumors of connective tissue. Am J Cancer
1935; 25: 630.
8 Moustafa MFH, Abdel-Fattah MA. Presumptive evidence of the
effect of pregnancy estrogens on keloid growth. Plast Recons Surg
1975; 56: 450–453.
9 Sandler B. Recurrent plantar keloid. Cutis 1999; 63: 325 –326.
?L
LETTERS
Letter
etter
162002
Antifungal activity of 33% grapefruit–water
glycerol solution
To the Editor
Grapefruit seed extract (GSE) was originally developed by the
German physicist and immunologist, Dr Jacob Harish, as an
antiparasitic agent. GSE contains polyphenolic compounds
including quercitin, helperidin, campherol glycoside, neohelperidin, naringenin, apigenen, rutinoside and poncirin.1,2 Tests
conducted by the United States Department of Agriculture
(USDA) in the early 1980s confirmed that Cricidal, as it was
then called, was effective in inhibiting viral strains in cattle and
dogs, and was approved for use by the USDA Evian Influenza
Eradication Programme in 1984. GSE has also been tested by
the USDA Pasteur Institute and found to be a very effective
broad spectrum antibiotic that kills salmonella, Escherichia coli,
Candida, herpes, influenza, fungi, and others.
P Oztas,* E Calikoglu
Fatih University Faculty of Medicine, Department of Dermatology,
Alparslan Turkes cad. No:57, 06510 Emek, Ankara, Turkey,
*Corresponding author, tel. +903 12 2126262; fax +903 12 2213276;
E-mail: [email protected]
Table 1 MICs of 33% grapefruit–water glycerol solution against Candida albicans reference strain 10231 ATCC and 200 isolates of C. albicans on Sabouraud’s
and yeast nitrogen base media
Number of strains
Candida albicans reference
Sabouraud’s medium
YNB medium
Candida albicans isolates
Sabouraud’s medium
YNB medium
0.05
0.25
0.5
strain 10 231 ATCC
0
0
0
0
0
0
0
6
0
0
0
30
1
1.5
3
6.25
12.5
25
50
100
200
Mean MIC (mg/L + range)
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
12.5 + 0
6.25* + 0
4
75
81
38
68
40
26
8
10
2
4
1
5
0
1
0
1
0
5.9 + 12.6
1.8* + 2.4
*P < 0.001 versus Sabouraud’s medium. YNB, yeast nitrogen base.
© 2003 European Academy of Dermatology and Venereology JEADV (2003) 17, 469– 490
Letters 487
In order to define the antifungal activity of 33% grapefruit–
water glycerol solution (GWS; Cinatamani, Poland) we tested
it against Candida albicans reference strain 10231 ATCC, 200
fresh clinical isolates of C. albicans, seven isolates of nonC. albicans, 12 dermatophytes and 20 strains of mold. GWS was
dissolved in 1% DMSO. MICs were determined by the agar
dilution procedure according to the National Committee for
Clinical Laboratory Standards reference document M27-A for
yeasts, dermatophytes and molds.3 Sabouraud’s medium (SB)
and a yeast nitrogen base (YNB) were used. The enzymatic
activity of the yeast-like fungi was performed using the API ZYM
test (BioMeriux). All procedures were carried out according
to the manufacturer’s instructions. We evaluated the enzymatic
activity of the yeast-like fungi strains in five score sacle, before
and after the addition of GWS.
GWS had a mean MIC of 12.5 mg/ L against C. albicans
reference strain 10231 ATCC on SB and 6.25 mg/ L on YNB,
respectively. The mean MIC for the C. albicans isolates was 5.9
mg/ L on SB, and 1.8 mg/ L on YNB (Table 1). The mean MIC
of GWS against the seven non-C. albicans isolates was 36.6 mg /
L on SB, and 18.2 mg/ L on YNB. GWS had a mean MIC of
90 mg / L for Trichophyton mentagrophytes versus granulosum
after 5 days incubation, and 175 mg/ L after 15 days incubation.
The mean MIC of GWS against Epidermophyton floccosum
isolates was 150 mg/ L and 200 mg/ L against Trichophyton
rubrum and Trichophyton tonsurans isolates. GWS had MIC
over the test range of 6.25 –200 mg/ L for molds. The C. albicans
reference strain had enzymatic activity of 14 enzymes and
exposure to GWS inhibited the enzymatic activity of five
enzymes. Prior to GWS exposure, C. albicans isolates had enzymatic activity of 16 enzymes, but after exposure three enzymes
were inhibited. The highest enzymatic activity had leucine
arylamidase, N-acetyl-α-glucosamindase, esterase, lipase and
α-glucosidase.
The presence of nobiletin, sinensetin, quercetogetin, heptamethoxyflavone and tangeretin in the essential oils of different citrus species (grapefruit, lemon, clementine, sour orange
and sweet orange) was examined by high performance liquid
chromatography-mass spectrometry.4,5 The results revealed
that the application of the polymethoxylated fraction of the
above essential oils at a concentration of 1% in the culture
medium demonstrated the antifungal properties of these
flavones. Ikegawa et al.6 investigated the effects of the ethyl
acetate extract of grapefruit juice, orange juice and their components on the uptake of [3H]vincristine into adriamycin-resistant
human myelogenous leukaemia cells. The uptake was increased
by the extracts of grapefruit and orange juice by up to sevenand three-fold, respectively. The grapefruit juice components
dihydroxybergamottin and bergamottin significantly increased
the uptake, but their potencies were considerably weaker than
those of the orange juice components. Some authors suggest
that these components may become candidates of multidrug
resistance reversing agents in cancer chemotherapy.4,5
We found that 33% grapefruit–water glycerol solution
exerted potent antifungal activity against the yeast-like fungi
strains and lower activity against dermatophytes and molds.
E Krajewska-Kulak,†* C Lukaszuk,† W Niczyporuk‡
†Department of General Nursing, Mycological
Laboratory, Medical Academy in Bialystok, 15-096
Bialystok, ul. M. C. Sklodowskiej 7a, Poland, ‡Department
of Dermatology and Venereology, Medical Academy in
Bialystok, 15 – 879 Bialystok, ul. Sw. Rocha 3, Poland.
*Corresponding author, tel. and fax +48 8574 855 28;
E-mail: [email protected]
References
1 Fuhr U, Klittich K, Staib AH. Inhibitory effect of grapefruit juice and
its bitter principal, naringenin, on CYP1A2 dependent
metabolism of caffeine in man. Br J Clin Pharmacol 1993; 35:
431–436.
2 Merkel U, Sigusch H, Hoffmann A. Grapefruit juice inhibits
7-hydroxylation of coumarin in healthy volunteers. Eur J Clin
Pharmacol 1994; 46: 175 –177.
3 National Committee for Clinical Laboratory Standards. Reference
method for broth dilution antifungal susceptibility testing of yeasts.
Approved standard. Document M27-A. Villanova, PA: National
Committee for Clinical Laboratory Standards, 1997.
4 Horowitz RM, Gentilli B. Flavonoid constituents of Citrus.
In: Ngy S, Saw PE, Vldhuis MK, ed. Citrus Science and Technology,
Volume 1. Westport, CT: Avi Publishing 1977: 397–426.
5 Tirillini B. Grapefruit: the last decade acquisitions. Fitoterapia 2000;
71 (Suppl. 1): S29 – S37.
6 Ikegawa T, Ushigome F, Koyabu N et al. Inhibition of
P-glycoprotein by orange juice components, polymethoxyflavones in
adriamycin-resistant human myelogenous leukemia (K562/ADM)
cells. Cancer Lett 2000; 160: 21–28.
?L?etters
LETTERS
Letters
Smallpox scars – the only evidence of an
eradicated disease
To the Editor
There is a striking absence of photographs of smallpox scars in all
major textbooks of dermatology. It is worth noting that smallpox
scars bear testimony to the existence of the disease until 1977,
when the last case was detected.1 The global eradication of smallpox
was certified, based on intense verification in countries, by a
commission of eminent scientists in December 1979 and subsequently endorsed by the World Health Assembly in 1980. Today,
over 25 years since the last case was recorded, the only evidence that
we have of smallpox is by the way of scars that are characteristic
of the disease. After the passing of the current generation that
comprises people who have suffered from the disease and have
scars, even this evidence of the eradicated disease will disappear.
© 2003 European Academy of Dermatology and Venereology JEADV (2003) 17, 469–490

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