A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis.

In a 2-armed, double-blind, randomized clinical study, the efficacy in the treatment of recurrent herpes labialis of 5% acyclovir in a novel liposomal carrier (ethosome) was evaluated in comparison with that of a commercial 5% acyclovir cream (Zovirax cream) and that of a drug-free vehicle. Data were based on 61 herpetic episodes in 40 subjects. In a crossover arm in which the 2 active preparations were compared, the time to crusting of lesions was significantly shorter (P < .025) with the ethosomal acyclovir (1.8 days) than with the cream (3.5 days). Time to loss of crust was also significantly shorter (4.2 vs 5.9 days; P < .05). In a parallel arm in which all 3 preparations were compared, the time to crusting with the ethosomal acyclovir (1.6 days) was significantly shorter than the time with the acyclovir cream (4.3 days; P < .02) and the time with the drug-free vehicle (4.8 days; P < .005); in this arm, the shorter time to loss of crust for the ethosome (3.5 days), in comparison with the times for the cream (6.4 days) and the drug-free vehicle (6.1 days), did not reach statistical significance. Approximately 30% of all episodes treated with the ethosome were clinically abortive; this compared with 10% of those treated with the cream or the drug-free vehicle. No adverse effects were reported, other than minor burning sensations at the application site that lasted a few seconds after application and were evenly distributed between the investigated preparations. This pilot study suggests the improved clinical efficacy of the new liposomal preparation in comparison with Zovirax cream in the treatment of recurrent herpes labialis.

Lack of influence of cyclosporin A on levels of gingival procollagen types I and III mRNAs in rats of different ages.

Previous studies showed that gingival overgrowth following cyclosporin A (CsA) administration is not associated with an increase in interstitial collagen. It also was shown that CsA causes a significant decrease in collagen content within the gingival stroma. In order to determine whether this decrease is caused by down-regulation of collagen mRNA, the procollagen mRNA level in gingiva of young and old rats was measured correlated with the ratio of interstitial collagen to DNA in these regions. Hybridization of 32P-labelled cDNA probes for procollagen types I and III with total RNA extracted from the molar gingiva showed that administration of Csa did not change the steady-state levels of mRNAs for both procollagens in the gingiva of either young or old rats. The ratio of gingival interstitial collagen to DNA was significantly reduced in the CsA-treated animals (4.2 +/- 0.85) relative to the controls (7.8 +/- 1.6). It is concluded that the reduction in interstitial collagen following CsA treatment is not age-related, and is most probably caused by increased degradation rather by decreased biosynthesis.

p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas.

Immunohistochemically detectable levels of p53 may be seen early in the malignant transformation of some neoplasms. To determine if p53 is immunocytochemically detectable, and therefore presumptively abnormal, in oral dysplasias and in situ carcinomas, and to explore the natural history of p53 protein expression in these lesions, sequential biopsies from patients with lesions occurring in the same anatomic site were examined. Formalin-fixed, paraffin-embedded sections from 19 patients were evaluated immunohistochemically for p53 protein using antibody clones Pab1801 and BP53-12. With two exceptions, comparable results were observed with these antibodies. p53 protein was detected immunocytochemically in 6 of 13 patients with dysplasias; 3 of these progressed to p53-positive invasive carcinoma, one advanced to a more severe grade of p53-positive dysplasia, one developed into a p53-negative verrucous carcinoma, and one represented a p53-positive dysplasia developing five years after treatment of a p53-positive carcinoma. The p53-positive dysplasias, which were found in all subtypes (mild, moderate, severe), preceded histologic malignant change by months to years. p53 detection was evident in 4 of 6 patients with in situ lesions. Sequential biopsies of three of these lesions showed no change in lesion histology or p53 staining, and one lesion advanced to a p53-positive carcinoma. It is concluded that p53 protein may be detected early in the development of a subset of p53-positive oral squamous cell carcinomas. This phenomenon may be seen in dysplasias and in situ lesions, and it may have prognostic implications.

Perioperative hemodynamic changes in ischemic heart disease patients undergoing dental treatment.

Twenty patients with stable ischemic heart disease in functional capacity Class II-IV underwent dental treatment. Scaling was performed in seven patients without local anesthesia. In the remaining 13 patients, pain control for restoration placement was obtained by local anesthesia: in seven patients, the anesthetics contained epinephrine, while in six this drug was omitted. Heart rate, blood pressure, and electrocardiograph were continuously monitored during the dental session. All patients had elevated systolic blood pressure and rate pressure product during treatment. In the patients who received plain local anesthetics only, the elevation in systolic blood and rate pressures was, however, significantly lower than the ischemic threshold. Arrhythmia or ST segment depression of > or = 1 millimeter were not recorded in any of the subjects. In severely compromised ischemic heart disease patients undergoing routine dental procedures of limited chair time, plain local anesthesia seems to be the preferred analgesic modality.

Isolation and characterization of herpes simplex virus resistant to nucleoside analogs.

Herpes simplex virus type 1 was isolated from nine patients with herpes labialis who were not previously exposed to any antiviral agent. A significant variation in the growth of these isolates in BSC1 cells in the presence of 5-iodo-2'-deoxyuridine and acyclovir was observed. One of the isolates was highly resistant to 5-iodo-2'-deoxyuridine and acyclovir and failed to induce significant activity of thymidine kinase in cultures. Herpesvirus reisolated from the same patient 3 1/2 years later did not show significant changes in its resistance to acyclovir, suggesting that the patient has a latent infection with a drug-resistant virus.

Periodontal alterations in patients with pemphigus vulgaris taking steroids. A biannual assessment.

Periodontal health parameters and salivary cortisol were studied in 19 adult pemphigus vulgaris patients on chronic steroid therapy. The patient population was divided into non-medicated and medicated subjects at intake into the study. A significant difference between the 2 examinations, performed at an interval of 8.73 months +/- 4.35, was found in bleeding index (p less than 0.000 and p less than 0.04, respectively) and gingival recession (p less than 0.000 and p less than 0.009) in both groups. No changes occurred in alveolar bone height. Steroid therapy altered the bleeding index (R = 0.60 and R = 0.80) and gingival recession (R = 0.87 and 0.91) in a dose-related manner, and induced low salivary cortisol. The findings of this study would suggest suppression of the host inflammatory reaction, resulting in an alleged healthy clinical appearance of the periodontium.

Prolonged systemic administration of cyclosporin A affects gingival epithelium.

Gingival biopsies were obtained from 12 patients suffering from Behcet's disease who were treated with Cyclosporin A (CsA) for up to 20 months. Preparations were made for examination with both light and scanning electron microscopy (SEM). Along with known changes in the gingival epithelial structure observed following CsA treatment, we also found unusual clusters of needle-like crystallites embedded in the epithelium, mostly at the base of the acanthotic projections. Toluidin blue staining revealed increased numbers of both intact and degranulated mast cells in the attached epithelium. It is concluded that CsA affects the gingival epithelium and that the clinically observed enlargement of gingival tissue following prolonged treatment with CsA is due primarily to CsA-epithelial interaction.

Oral soft tissue status in an elderly institutionalized population.

A total of 1,037 oral soft tissue lesions (3.98 lesions per patient) was found in 260 elderly people of American/European and of Asian/African extraction residing in a home for senior citizens in Jerusalem. There was a strong association between wearing of dentures or usage of bare mucosa for masticatory purposes and the presence of specific lesions at typical locations. A significant difference was found between the two ethnic groups with respect both to pattern of tooth loss and utilization of rehabilitative means. The distribution of the oral soft tissue lesions among the participants in the study seemed to be linked to their cultural background.

[A latex agglutination test for the rapid identification of periodontally pathogenic microorganisms in subgingival plaque. The preliminary results]. / Der Latex-Agglutinationstest zur schnellen Identifizierung von parodontopathogenen Mikroorganismen in der subgingivalen Plaque. Vorläufige Ergebnisse.

Latex agglutination tests (LA) have been evaluated for identifying periodontal pathogens. This preliminary study compared LA tests with indirect immunofluorescence (IF) for the rapid identification of A. actinomycetemcomitans, B. gingivalis, and B. intermedius in clinical subgingival plaque samples. A total of 58 sites from 12 patients suffering from advanced periodontitis, exhibiting recent attachment loss were examined before and after initial periodontal treatment. The results of the two examinations were pooled and a total of 116 sites were statistically evaluated. The overall agreement between LA and IF was 75.8% for black pigmented Bacteroides (BPB) and 74.1% for Aa. These results demonstrate the feasibility of LA as a rapid, inexpensive, and reliable tool for monitoring periodontal disease offered to the general practitioner.

Glycyrrhizin gel as vehicle for idoxuridine topical preparation: skin permeation behaviour.

The in vitro skin permeation behaviour of idoxuridine (IDU) from a new preparation containing glycyrrhizin gel as carrier was tested and compared with that from a commercial IDU ointment (Virusan) at two temperatures on intact and stripped skin. At 34 degrees C the normalized flux (Fn) values were six times higher for the IDU glycyrrhizin gel than for Virusan when tested on intact hairless mouse skin. At 25 degrees C, Fn values were 22 and 25 times greater for the gel formulation using intact and stripped skin, respectively. These in vitro results, showing that IDU penetrates the skin more effectively when incorporated in the glycyrrhizin gel than in the ointment, correlate well with the previously reported efficacy of the gel tested in vivo.

The effect of cyclosporin A (CsA) treatment on gingival tissue of patients with Behçet's disease.

Gingival biopsies were obtained at various intervals for a period of two years from 12 patients suffering from Behçet's disease who were under a clinical trial of cyclosporin A (CsA) treatment. The levels of nondialyzable hydroxyproline (Hypro) were determined in the medium of the cultured tissues. Histologic examinations were also performed every three months. Correlations between the CsA blood levels and the levels of nondialyzable Hypro indicated a reciprocal relationship, especially at blood levels of CsA higher than 600 ng/ml. Histologic examination of gingival sections from CsA-treated patients showed swelling of the epithelial cells, formation of perinuclear clear zones, widening of intercellular gaps and formation of several basal cell layers. In addition, foci of PAS-positive material were found in both the epithelium and stroma. It is assumed that the gingival enlargement observed in the CsA-treated patients was not due to an increase in tissue collagen but rather to an increase in epithelium combined with an accumulation of noncollagenous extracellular matrix material.

Lichen planus evoked by periodontal surgery.

A case of Lichen Planus (LP) following periodontal surgery in a patient previously free of the disease is described. Genetic predisposition and lymphokine secretion stimulated by local trauma are suggested as a possible mechanism of the phenomenon. It is recommended that LP patients, especially those suffering from the erosive type, should be treated as conservatively as possible, minimizing the possibility of trauma to the oral tissues where local immunity may have been altered by a pathological process.

HLA-B51 may serve as an immunogenetic marker for a subgroup of patients with Behçet's syndrome.

Epidemiologic data, family history, clinical data, HLA typing, neutrophilic chemotaxis, and immunofluorescence of clinically normal non-sun-exposed skin were studied in 46 Israeli non-Ashkenazi Jewish and Arab patients with Behçet's syndrome. HLA-B51 was present in 71 percent of the patient group as compared with 13 percent of the control group (relative risk = 17.1). In four of 30 families in the B51-positive group, there was a close relative of the proband with Behçet's syndrome who was carrying the HLA-B51 antigen. Neutrophilic chemotaxis in this group was enhanced in 80 percent of the patients, and in most patients no deposition of immunoglobulin in the dermo-epidermal junction was observed, whereas C3 was present in papillary vessels. In the B51-negative group, the family history was negative for Behçet's syndrome, neutrophilic chemotaxis was enhanced in only two of eight patients, and in four of six patients, IgM deposition was detected in the dermo-epidermal junction. It is concluded that in Israeli non-Ashkenazi Jews and Arabs, there is a significant association between HLA-B51 and the risk of developing Behçet's syndrome. The B51-positive patient group has a family history of the disease, enhanced neutrophilic chemotaxis, and a lack of immunoglobulin deposition in the dermo-epidermal junction.

Glycyrrhizin gel as a vehicle for idoxuridine--I. Clinical investigations.

The therapeutic efficacy of a new formulation that incorporates 0.2% IDU in glycyrrhizin gel has been tested on patients who suffer from herpes of the lips and nose. The preparation was significantly more effective than a commercial 0.5% IDU ointment. It reduced the healing time and produced an almost instantaneous relief from pain. The higher efficacy of the new preparation may be ascribed to the reported anti-inflammatory and antiviral activities of glycyrrhizin together with an enhanced permeation of the IDU through the skin.

Vaginal and oral cytology of the menopause. A comparative study.

A comparative cytologic study was made of the hormonal content of the vaginal and oral mucosa of menopausal women. Twenty-three women between one and ten years (early menopause) and 33 patients more than ten years (late menopause) after cessation of menstruation had oral and vaginal smears taken. Comparable smears from 21 young women, and oral smears from 18 males served as controls. The smears were evaluated by the maturation value method, and averages were established for each group. The vaginal smears had low maturation values of 40 and 22 in the early and late menopausal groups, respectively. In these women, the buccal smears' maturation values were high, above 70. Similar high maturation values were found in buccal smears of the young women and men. It was concluded that the high maturation values found in the oral smears of the menopausal women are not the result of hormonal effect but that of local mechanisms or irritative factors.

Anticariogenic activity of licorice and glycyrrhizine I: Inhibition of in vitro plaque formation by Streptococcus mutans.

The effect of licorice and its active sweet component glycyrrhizin was tested on the growth and adherence to glass of the cariogenic Streptococcus mutans. Neither licorice nor glycyrrhizin promoted growth or induced plaque formation. In the presence of sucrose, glycyrrhizin did not affect bacterial growth, but the adherence (plaque formation) was markedly inhibited. At 0.5-1% glycyrrhizin, inhibition was almost complete. These results support our previous suggestions that glycyrrhizin might serve as an efficient vehicle for topical oral medications.