Oral manifestations of sexually transmitted infections.

It's difficult to establish the real risks associated with all forms of oral sex and the contribution they may make to the overall number of newly diagnosed cases of sexually transmitted infections (STIs). This article reviews the literature on the role of oral sex in the transmission of STIs and the corresponding clinical presentations. Oral sex is becoming a common sexual practice between both heterosexual and homosexual couples because it is seen as a safer alternative to penetrative sex and a safer challenge to an individual's hidden identity. Because of the frequency with which oral sex occurs, and the rarity with which it is protected, oral sex may raise justified alarming attention to underestimated orally acquired STIs.

Sexually transmitted diseases syndromic approach: proctitis.

Proctitis is a common problem and is most frequently associated with inflammatory bowel diseases (IBD). However, in the last ten years the incidence of infectious proctitis appears to be rising, especially in men who have sex with men. This may be due to the rise of people participating in receptive anal sex as well as the increase in sexually transmitted infections, such as those from Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus and Treponema pallidum. Recent outbreaks of lymphogranuloma venereum among homosexual men throughout Europe highlight the need to consider sexually transmitted infections in the differential diagnosis of proctitis. Symptoms of infectious proctitis can include rectal blood and mucous discharge, anorectal pain, aphtous ulcers and, sometimes, generalized lymphadenopathy and fever. A careful history and physical examination are crucial in establishing a diagnosis, eventually supported by endoscopy, histology, serology, culture and PCR. Treatment with antibiotics or antivirals is usually initiated, either empirically or after establishing a diagnosis. Coinfections, HIV testing, and treatment of sexual partners should always be considered.

Off label treatments of genital warts: the role of photodynamic therapy.

Conventional therapies for genital warts, the clinical expression of low-risk human papillomavirus (HPV) anogenital infection, are not targeted antiviral therapies, but either attempt physical removal of the lesion or induce inflammation and a bystander immune response. Moreover, very few of the current treatments have been tested by rigorous blinded, randomized controlled trials. Therefore, official recommendations are often associated with unsatisfactory response rates and high recurrence rates. It is the purpose of this review to provide a brief overview of the genital wart treatment literature to expand awareness of the options available to practitioners faced with patients presenting with this disease. Particular attention will be paid to unconventional and complementary therapies (the so called "off-label" treatments) among which photodynamic therapy has been recently introduced as a promising strategy to both guarantee clearance of the lesion and eradication of the virus itself. Mechanisms of action of PDT are discussed together with a summary of clinical and experimental available evidences.

Arylsulfonyl-N,N-dialkyl-dithiocarbamates as tumor cell growth inhibitors: novel agents targeting beta-tubulin?

Reaction of sodium N,N-dimethyldithiocarbamate or N,N-diethyldithiocarbamate with arylsulfonyl halides afforded a series of arylsulfonyl-N,N-dialkyl-dithiocarbamates. The reactivity of these new derivatives with cysteine and glutathione has been investigated in order to identify derivatives that might label a cysteine residue of the heterodimeric protein tubulin which plays a critical physiological function in cell division and also possesses enzymatic activity as a GTP-ase. Since many antitumor drugs exert their action by binding to tubulin, inhibiting in this way microtubule association and provoking cell death, some of the most reactive compounds against the thiol reagents found in this work have been assayed for their antitumor activity. Indeed strong tumor cell growth inhibitory properties against several leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer has been found in vitro for some of the 4-halogeno-, 4-methyl- or 4-carboxyphenyl-substituted arylsulfonyl-N,N-dialkyl-dithiocarbamates. Furthermore, some of these derivative were shown to act as in vitro tubulin polymerization inhibitors using a turbidimetric assay.

Antimycobacterial activity of 9-sulfonylated/sulfenylated-6-mercaptopurine derivatives.

A series of 9-sulfonylated/sulfenylated-6-mercaptopurines has been prepared by reaction of 6-mercaptopurine with sulfonyl/sulfenyl halides. These compounds constitute a new class of potent antimycobacterial agents, possessing MIC values against Mycobacterium tuberculosis H37Rv in the range of 0.39-3.39 microg/mL, as well as appreciable activity against Mycobacterium avium. Furthermore, a compound of this small series exhibited good activity (MIC under 1 microg/mL) against several drug resistant strains of M. tuberculosis.

Antimycobacterial activity of 3,4-dichlorophenyl-ureas, N,N-diphenyl-ureas and related derivatives.

Substituted urea derivatives were prepared by reacting 3,4-dichlorophenyl isocyanate with amino acids, dipeptides, histamine or dicyandiamide among others, or from N,N-diphenyl-carbamoyl chloride and amino acids, dipeptides, or histamine. Other derivatives were obtained by reaction of PABA or PAS with arylsulfonyl halides. Some of the new compounds showed appreciable activity as antimycobacterial agents against Mycobacterium tuberculosis H37Rv, producing an inhibition of growth in the range of 80-89%, at a concentration of 6.25 microM. Some derivatives of this series might constitute interesting lead molecules for designing novel types of drugs effective against M. tuberculosis, a re-emerging pathogen both in the developed and under-developed countries.

4-toluenesulfonylureido derivatives of amines, amino acids and dipeptides: a novel class of potential antitumor agents.

The screening of a series of arylsulfonylureido derivatives of amines (such as histamine, or dopamine), aliphatic/aromatic amino acids (such as Gly, beta-Ala, Val, Lys, Arg, Phe, Tyr, DOPA, etc.) and dipeptides (such as GlyGly, beta-AlaHis) led to the identification of three derivatives that possess tumor growth inhibitory properties against several leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, and breast cancer cell lines in vitro. The new derivatives were prepared by reaction of 4-toluenesulfonyl isocyanate with (protected) amines, amino acids or dipeptides. The mechanism of antitumor action with these new derivatives is not known at the moment but it may imply uncoupling of mitochondria, as for the structurally related diarylsulfonylurea sulofenur, an investigational anticancer agent.

Arylsulfonyl-N,N-diethyl-dithiocarbamates: a novel class of antitumor agents.

A series of alkyl/arylsulfonyl-N,N-diethyl-dithiocarbamates has been prepared by reaction of sodium N,N-diethyldithiocarbamate with alkyl/arylsulfonyl halides. The reactivity of these new derivatives against cysteine and glutathione has been investigated in order to identify derivatives that might label a critical cysteine residue of tubulin (Cys 239 of human beta2 tubulin chain). Some of the most reactive compounds showed moderate to powerful tumor growth inhibitory properties against several leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer cell lines in vitro.

Antifungal activity of silver and zinc complexes of sulfadrug derivatives incorporating arylsulfonylureido moieties.

Two well known antimicrobial sulfonamides, sulfadiazine and sulfamerazine were reacted with arylsulfonyl isocyanates, affording several new arylsulfonylureido derivatives. These compounds were subsequently used as ligands (in the form of conjugate bases, as sulfonamide anions) for the preparation of metal complexes containing silver and zinc. The newly synthesized complexes, unlike the free ligands, proved to act as effective antifungal agents against several Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.5-5 microg/ml. The mechanism of antifungal action of these complexes seems to be different from that of the azole antifungals acting as lanosterol-14-alpha-demethylase inhibitors. Levels of sterols assayed in the fungi cultures treated with these new antifungals were equal in the absence or in the presence of the tested compounds. This is in strong contrast with similar experiments in which ketoconazole has been used as antifungal, when drastically reduced ergosterol amounts could be detected. Thus, it is probable that the inhibition of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls, imparts antifungal activity to the new metal complexes reported here.

Antifungal activity of Ag(I) and Zn(II) complexes of aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) derivatives.

Aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), being at the same time structurally similar to the antimicrobial sulfonamides. Here we report that the reaction of aminobenzolamide with arylsulfonyl isocyanates affords a series of new arylsulfonylureido derivatives which were subsequently used as ligands (in the form of conjugate bases, as sulfonamide anions) for the preparation of metal complexes containing Ag(I) and Zn(II). All the new compounds proved to be very potent inhibitors of CA (isozymes I, II and IV). The newly synthesized complexes, unlike the free ligands, also act as effective antifungal agents against several Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.8-5 microg/mL. The mechanism of antifungal action of these complexes seem to be unconnected with inhibition of lanosterol-14-alpha-demethylase, since the levels of sterols assessed in the fungi cultures were equal in the absence or in the presence of the tested compounds. Probably the new complexes act as inhibitors of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls.

The antifungal activity of sulfonylated/carboxylated derivatives of dibenzo-1,4-dioxine-2-acetyloxime may be due to inhibition of lanosterol-14alpha-demethylase.

Aryl/alkyl-sulfonyl-, aryl/alkylcarboxyl- and aryl(sulfonyl)carbamyl/thiocarbamyl-derivatives of dibenzo-1,4-dioxine-2-acetyloxime were prepared by reaction of the title compound with sulfonyl halides, sulfonic acid anhydrides, acyl chlorides/carboxylic acids, arylsulfonyl isocyanates, aryl/acyl isocyanates or isothiocyanates. Several of the newly synthesized compounds showed effective in vitro antifungal activity against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole (with minimum inhibitory concentrations in the range of 1.2-4 microg/mL) against the two Aspergillus strains, but possessing a lower activity as compared to ketoconazole against C. albicans. Of the three investigated strains, best activity was detected against A. flavus. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis by interaction with lanosterol-14-alpha-demethylase (CYP51A1), since reduced amounts of ergosterol were found by means of HPLC, in cultures of the sensitive strain A. flavus treated with some of these inhibitors. Thus, the compounds reported here might possess a similar mechanism of action at molecular level with that of the widely used azole antifungals.

Antifungal Activity of Ag(I) and Zn(II) Complexes of Sulfacetamide Derivatives.

Reaction of sulfacetamide with arylsulfonyl isocyanates afforded a series of derivatives which were used as ligands (as conjugate bases) for the preparation of metal complexes containing Ag(I) and Zn(II). The newly synthesized complexes, unlike the free ligands, act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3 - 0.5 mug/mL. The mechanism of antifungal action of these complexes seems to be not connected with the inhibition of lanosterol-14-alpha-demethylase, since the levels of sterols assessed in the fungi cultures were equal in the absence or in the presence of the tested compounds. Probably the new complexes act as inhibitors of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls.

Keratosis palmoplantaris varians of Wachters.

We report a case of hereditary palmoplantar keratosis (HPPK) causing a progressive reduction of the prehension capacity of the fingers due to the presence of hyperkeratotic lesions which had appeared approximately 25 years earlier. These lesions, also involving the soles, appeared yellowish in color, linear or round in shape, symmetrical and often confluent, developed prevalently at the pressure points displaying a non-transgrediens pattern. The histological examination, clinical picture and careful analysis of the literature enabled us to define this form as 'keratosis palmoplantaris varians of Wachters'. As a contribution to a conclusive HPPK classification we discuss the differential diagnosis of this disorder most commonly identified through nummular-linear keratoses also known as Siemens' syndrome.

[Sexually transmitted diseases in adolescents: clinico-epidemiologic findings]. / Le malattie a trasmissione sessuale negli adolescenti: rilievi clinico-epidemiologici.

Estimates of the global prevalence and incidence of sexually transmitted diseases in adolescents are limited. Recent prevalence estimates report over 333 million cases of the four major curable STDs in adults between the ages of 15 and 49: 12 million cases of syphilis, 62 of gonorrhoea, 89 of chlamydia, and 170 of trichomoniasis. The vast majority of these cases are in developing countries such as East Asia and Pacific, Sub-Saharan Africa, Latin American and Caribbean where syphilis and gonorrhoea still have a high prevalence. However, CT genital infection is the most commonly reported bacterial STD. In 1996 this infection had been the most common of the nationally notifiable infectious disease in the United States and was estimated that there were 2.5-3.3 million new cases per year. It resulted that African-American adolescents 14 to 19 years of age have the highest rates of STDs of any racial/ethnic group of adolescents. In addition, viral "non-curable" STDs have become a prominent public health issue over recent years due to a marked increase in prevalence of HSV and HPV infections. In the United Kingdom the annual number of genital herpes has almost tripled during the past 15 years. It is now evident that the high rate of HSV asymptomatic infection plays an important and complex role in estimating epidemiological data. To date, HPV genital infection probably represents the most frequent STD. The young age of sexual activity onset and lifetime number of sexual partners are considered the highest behavioral risk factors.

Desmoplastic trichoepithelioma.

A 20-year-old male presented with a 4 year history of a solitary nodule, 8 mm in diameter on the left temple. It was covered by normal skin, with a central depression and elevated borders. Histopathology showed numerous horn cysts amidst nests and strands of basaloid cells surrounded by a dense fibrous stroma. The clinical and histopathological features were characteristic of desmoplastic trichoepithelioma.

Multicentre clinical trial with herpes simplex virus vaccine in recurrent herpes infection.

The aim of this work was to confirm our preliminary clinical and immunological evaluation of the protective effects of a herpes simplex virus (HSV) vaccine derived from killed virus in the treatment of relapsing facial or genital herpes simplex infection. A total of 142 patients were treated with the HSV vaccine and a control group of 50 were treated with intermittent oral acyclovir (ACV). The vaccine reduced annual active disease days in vaccinees to 11.59 (+/- 15.3) after treatment (65.11 +/- 31.64 before treatment) compared to 30.4 +/- 17.49 days after treatment of the control group patients (71.86 +/- 32.5 before treatment).