Dermatophyte agents in the city of São Paulo, from 1992 to 2002

Dermatophytosis are superficial mycoses caused by fungi that can invade stratum corneum and keratinized tissues. In order to study the frequency of dermatophytes species and the clinical manifestations caused by these fungi, in S?o Paulo, SP, Brazil, the authors analyzed cultures isolated at the Mycology Laboratory from a selected population (15,300 out-patients of the Hospital das Clínicas, Department of Dermatology, Faculty of Medicine of University of S?o Paulo) from January 1992 to June 2002. The most prevalent dermatophyte was Trichophyton rubrum (48.7%), followed by Microsporum canis (20.9%), Trichophyton tonsurans (13.8%), Trichophyton mentagrophytes (9.7%), Epidermophyton floccosum (4.1%), and Microsporum gypseum (2.5%). These agents determined more than one clinical manifestation, i.e., tinea corporis (31.5%), tinea capitis (27.5%), tinea unguium (14.8%), tinea cruris (13.9%), tinea pedis (9.9%), and tinea manuum (1.9%). Clinical variants of dermatophytosis and their relationship to the etiologic agents were studied and the results were compared to those obtained in previous studies in other regions of Brazil and in other countries.     

Antifungal Agents,II: Synthesis and Antifungal Activities of Aryl-1H-pyrrol-2-yl-1H-imidazol-1-yl-methane Derivatives with Unsaturated Chains

The synthesis and antifungal activities of aryl-1H-pyrrol-2-yl-1H-imidazol-1-yl-methanes having allyl, crotyl, and acrylate chains linked to the N-pyrrole atom and substituted at phenyl ring by Cl, F, CH₃, and NO₂ groups are reported. In vitro tests against Candida albicans and Candida spp. showed 2,4-dichlorophenyl-1-allyl-1H-pyrrol-2-yl-1H-imidazol-1-yl-methane to be the most potent derivative with activities comparable to those of ketoconazole and slightly inferior to those of bifonazole and miconazole. Some structure-activity relationships are discussed.     

Osteocyte-Bone Lining Cell System at the Origin of Steady Ionic Current in Damaged Amphibian Bone

A wound-generated steady electric current was measured by a two-dimensional vibrating probe system in the metatarsal bones of 22 adult frogs (Xenopus laevis) placed in amphibian Ringer. Inward currents were recorded entering a micrometric hole drilled through the cortex at middiaphyseal level. These steady state currents (mean ± SD 8.50 ± 2.77 μA/cm²) last approximately 2 hours, were dependent on the presence of sodium in the incubation medium, were no more detectable after fixation, and were reduced to background level when the cell membranes were solubilized. These results agree with previous recordings of metatarsal bones of weanling mice, under identical conditions. Both results suggest that the measured ionic currents have a cellular origin. Metatarsal bones of adult amphibian were purposely selected for this study because, unlike mammalian bones, their shafts are avascular and only contain an osteocyte-bone lining cell system, as documented by scanning and transmission electron observations. Thus, unlike the data from previous investigations on mammals, the results succeeded in giving the first convincing evidence that the osteocyte-bone lining cell system is the origin of damage-generated ionic currents. As damage exposes bone ionic compartment to plasma, damage-generated ionic currents are representative of ion fluxes at bone plasma interface, and cells at the origin of the current generate the driving force of such fluxes. By demonstrating that osteocytes and bone lining cells are at the origin of the current, this study suggests that the osteocyte-bone lining cell system, though operating as a cellular membrane partition, regulates ionic flow between bone and plasma. Since strain-related adaptive remodeling could also depend on ionic characteristics and flow of the bone fluid through the osteocyte lacuno-canalicular network, the results reported here support the view that osteocyte and bone lining cells may constitute a functional syncytium involved in mineral homeostasis as well as in bone adaptation to mechanical loading.     

HIV-1 Tat protein mimicry of chemokines

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL_24–51) encompassing the “chemokine-like” region of Tat induced a rapid and transient Ca²⁺ influx in monocytes and macrophages, analogous to β-chemokines. Both monocyte migration and Ca²⁺ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of β-chemokines from the β-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL_24–51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic β-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.     

AIDS related neoplasms in Genoa,Italy

The study defines the epidemiological characteristics of HIV-infection in the population of Genoa and estimates the entity of AIDS-cancer association. The cohort includes 317 subjects resident in the Municipality of Genoa, aged above 14 years and notified prior to 31 December 1991 and/or dead from AIDS in the period 1988–1991. From 1984 to 1991, 44 cases of tumour were recorded. The comparison between the rate ratios found in the AIDS patients' cohort and in the general population of Genoa strengthen the significant association highlighted in literature regarding overall cancer, 26.7 (p<0.05), and in particular, Kaposi's sarcoma, 3239.4 (p<0.05); non-Hodgkin's lymphomas, 84.8 (p<0.05); Hodgkin's lymphomas, 20.6 (p<0.05). Moreover, a significant increase in the risk of testicular seminoma, 61.5 (p<0.05) and lung cancer, 18.0 (p<0.05) is confirmed.     

Nle4,D-Phe7]alpha-MSH improves functional recovery in rats subjected to diencephalic hemisection

Rats subjected to diencephalic hemisection were s.c. treated with alpha-MSH (20 micrograms/rat daily) or with [Nle4,D-Phe7]alpha-MSH (10 micrograms/rat every other day) for two weeks starting on day 3 after lesion. Apomorphine-induced (1 mg/kg s.c.) rotational behavior was studied on days 7, 14 and 21 after lesion, and a sensorimotor test battery was carried out on days 3, 10, 17 and 24 after lesion. [Nle4,D-Phe7]alpha-MSH greatly reduced rotational behavior and significantly improved sensorimotor performance. Histological studies showed that treatment with alpha-MSH and, even more markedly, with [Nle4,D-Phe7]alpha-MSH reduced the size of the lesion and the pseudoinflammatory reaction, and caused a marked proliferation and hypertrophy of astroglia. Binding studies showed that no supersensitivity of striatal dopamine receptors developed on the lesioned side of alpha-MSH- and [Nle4,D-Phe7]alpha-MSH-treated rats. The present results seem to further support the trophic role of MSH peptides on nerve tissue.     

A <Emphasis Type="Italic">novel</Emphasis> heterozygous <Emphasis Type="Italic">missense</Emphasis>mutation in the UMOD gene responsible for Familial Juvenile Hyperuricemic Nephropathy

Background  

Familial Juvenile Hyperuricemic Nephropathy is an autosomal dominant nephropathy, characterized by decreased urate excretion and progressive interstitial nephritis. Mutations in the uromodulin coding UMOD gene have been found responsible for the disease in some families.     

A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833

Several recent reports have demonstrated a role for selective cannabinoid CB2 receptor agonists in pain modulation, showing both analgesic and antihyperalgesic activities. While the mechanism of action is poorly understood, it has been postulated that these effects may be indirect, involving release of endogenous opioids. We have previously reported that administration of the selective cannabinoid CB2 receptor agonist GW405833 (2,3-dichloro-phenyl)-[5-methoxy-2-methyl-3-(2-morpholin-4-yl-ethyl)-indol-1-yl]-methanone) to rats elicits potent and efficacious antihyperalgesic effects against neuropathic and inflammatory pain and, at high dose (100 mg/kg), is analgesic and ataxic [Valenzano, K.J., Tafesse, L., Lee, G., Harrison, J.E., Boulet, J., Gottshall, S.L., Mark, L., Pearson, M.S., Miller, W., Shan, S., Rabadi, L., Rotstheyn, Y., Chaffer, S.M., Turchin, P.I., Elsemore, D.A., Toth, M., Koetzner, L., Whiteside, G.T., 2005. Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology 48, 658-672]. In the current study, we confirm these properties using mouse models and investigate the role of cannabinoid CB2 receptors using knockout animals. Furthermore, we provide evidence that the antinociceptive properties of GW405833 are opioid independent. GW405833 elicited robust antihyperalgesic effects in mouse models of inflammatory (Freund's complete adjuvant) and neuropathic (Seltzer) pain. In contrast, GW405833 showed no antihyperalgesic activity against Freund's complete adjuvant-mediated inflammatory pain in cannabinoid CB2 receptor knockout mice. As in rats, high-dose GW405833 (100 mg/kg) showed both analgesic and sedative activities in wild-type mice, activities that were also apparent in cannabinoid CB2 receptor knockout mice. In rats, neither the antihyperalgesic effect in the Freund's complete adjuvant model nor the analgesic effects in tail flick and hot plate assays were inhibited by pre-treatment with the non-selective opioid receptor antagonist, naltrexone. These data demonstrate that the antihyperalgesic effects of GW405833 are mediated via the cannabinoid CB2 receptor, whereas the analgesic and sedative effects are not. Furthermore, these data suggest that the mechanism of action for GW405833 does not depend on the release of endogenous opioids.