Melanoma Awareness Among Medical Students.

Melanoma is the most aggressive skin cancer. Since diagnosis is visual, it is critical to evaluate if students acquire enough knowledge for early detection during medical school. To assess the melanoma knowledge of first-year (freshman) and sixth-year (senior) medical students, in a Brazilian Institution. It was a transversal and quantitative study. A questionnaire with sociodemographic data, knowledge about melanoma, and the habit of skin self-exam was filled out by medical students. A total of 128 first-year and 122 seniors students were included. All the sixth-year students knew melanoma as a skin cancer compared with 46.09% of the first-year students. Melanoma clinical characteristics were known by 30.51% of the freshman and 97.54% of seniors. However, they did not know the most usual site of melanoma occurrence (79.66% of first-year students and 24.59% of senior). About the skin self-exam, only 50% of first-year students and 53.28% of senior had the habit of doing it sometimes. Medical school was effective in providing knowledge about melanoma and its features. However, this was not reflected in an increase in the number of students that did the skin self-exam, which indicates the need for new approaches in teaching.

Atypical Exciton-Phonon Interactions in WS2 and WSe2 Monolayers Revealed by Resonance Raman Spectroscopy.

Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first-optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic).

Population genetic structure of Attalea vitrivir Zona (Arecaceae) in fragmented areas of southeast Brazil.

Attalea vitrivir Zona (synonym Orbignya oleifera) is one of the six species of Arecaceae known as "babassu". This species is used to make cosmetics, food, and detergents due to the high concentration of oil in the seeds. It is found only in fragmented areas of southern Bahia State and northern Minas Gerais State, southeast Brazil, and this fragmentation has affected both its ecological and genetic characteristics. We evaluated the genetic diversity and population genetic structure of A. vitrivir in six areas of two different regions at the extremes of its geographical range, in order to gain a better understanding of the factors that affect the distribution and partitioning of its diversity. Nine inter simple sequence repeat (ISSR) markers amplified 74 polymorphic bands, resulting in large diversity values (Shannon diversity index, 0.37-0.47; intrapopulation genetic diversity, 0.25-0.34). Analysis of molecular variance (AMOVA) revealed considerable differentiation between sampling sites (30.03%) and regions (12.08%), although most of the diversity was observed within sampling sites (69%). Further differentiation between sampling sites was noted more in the northern region than in the southern region, highlighting the genetic connectivity between the sampling sites within Rio Pandeiros Environmental Protection Area (southern region). The identification of two distinct genetic clusters (K = 2) corresponded to the northern and southern regions, and corroborated the AMOVA results. We suggest that the northern area, outside Rio Pandeiros Environmental Protection Area, must be included in future management plans for this species.

Preparing for the Implementation of Long-Acting Injectable Cabotegravir for HIV Pre-Exposure Prophylaxis Within the Brazilian Public Health System (ImPrEP CAB Brasil): Qualitative Study.

BACKGROUND: Although long-acting, injectable cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention in clinical trials, research is needed to guide effective implementation in real-world settings. Formative work with community members and health care providers (HCPs) is important to provide insight into the needs and contexts of specific populations and reveal potential barriers and facilitators for implementation projects. OBJECTIVE: We aimed to describe the results from formative work to develop an implementation package for CAB-LA PrEP within the ImPrEP CAB Brasil study. METHODS: ImPrEP CAB Brasil is an implementation study of same-day delivery of CAB-LA PrEP for young sexual and gender minority (SGM) groups (aged 18-30 years) in 6 existing oral PrEP public health clinics. We conducted formative research to prepare for the implementation of ImPrEP CAB Brasil through community mobilization, process mapping with HCPs with experience in CAB-LA, and focus group discussions (FGDs) with young SGM groups (n=92) and HCPs (n=20) to identify initial perceptions of facilitators and barriers for CAB-LA PrEP implementation, refine the mobile health (mHealth) educational tool, and evaluate the acceptability of using a text message appointment reminder intervention through WhatsApp. FGDs were recorded, transcribed, systematically coded, and analyzed with thematic categorization by trained researchers using a qualitative data analysis program ATLAS.ti (version 7). RESULTS: A community mobilization team comprising 34 SGM community leaders collaborated in creating a prototype for an mHealth educational tool and contributed to the planning of peer education activities. We created 3 process maps for each site to describe the initial visit, follow-up visits, and laboratory flow. The main challenge identified for same-day CAB-LA PrEP delivery was the extended duration of clinic visits due to the numerous laboratory tests and HIV counseling steps required. Proposed solutions included having point-of-care HIV rapid tests instead of laboratory tests and additional counseling staff. Barriers for CAB-LA PrEP implementation identified through FGDs were the training of HCPs, support for adherence to injection appointments, and stigma or discrimination against SGM groups and persons using PrEP. The mHealth educational tool and WhatsApp reminders were highly acceptable by SGM groups and HCPs, indicating their potential to support PrEP choice and adherence. Content analysis on the cultural appropriateness of the language and overall clarity of the material contributed to the refinement of the mHealth tool. CONCLUSIONS: Structured formative work with SGM persons and HCPs generated important refinements to context-specific materials and plans to launch ImPrEP CAB Brasil in public health clinics. Ongoing implementation monitoring will use the process maps to identify additional barriers and potential solutions to same-day delivery of CAB-LA PrEP. Summative evaluations are needed to measure the effectiveness of the mHealth educational tool to support PrEP choice and the use of WhatsApp appointment reminders.

Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study.

Background: HIV incidence estimation is critical for monitoring the HIV epidemic dynamics and the effectiveness of public health prevention interventions. We aimed to identify sexual and gender minorities (SGM) with recent HIV infections, factors associated with recent HIV infection, and to estimate annualised HIV incidence rates. Methods: Cross-sectional multicentre study in HIV testing services in Brazil and Peru (15 cities). Inclusion criteria: 18+ years, SGM assigned male at birth, not using pre-/post-exposure prophylaxis. We identified recent HIV infection using the Maxim HIV-1 LAg-Avidity EIA assay as part of a recent infection testing algorithm (RITA). Annualized HIV incidence was calculated using the UNAIDS/WHO incidence estimator tool. Multivariable logistic regression models were used to estimate factors associated with recent HIV infection. Trial registration: NCT05674682. Findings: From 31-Jan-2021 to 29-May-2022, 6899 individuals participated [Brazil: 4586 (66.5%); Peru: 2313 (33.5%)]; 5946 (86.2%) cisgender men, 751 (10.9%) transgender women and 202 (2.9%) non-binary/gender diverse. Median age was 27 (IQR: 23-34) years. HIV prevalence was 11.4% (N = 784/6899); 137 (2.0%) SGM were identified with recent HIV infection. The overall annualized HIV incidence rate was 3.88% (95% CI: 2.86-4.87); Brazil: 2.62% (95% CI: 1.78-3.43); Peru: 6.69% (95% CI: 4.62-8.69). Participants aged 18-24 years had higher odds of recent HIV infection compared to those aged 30+ years in both countries. Interpretation: Our results highlight the significant burden of HIV epidemic among SGM in large urban centres of Brazil and Peru. Public health policies and interventions to increase access to effective HIV prevention methods such as PrEP are urgently needed in Latin America. Funding: Unitaid, WHO (Switzerland), Ministry of Health from Brazil and Peru.

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Modeling the effects of low-LET cosmic rays on electronic components.

The effects of cosmic radiation in single cells, organic tissues and electronics are a major concern for space exploration and manned missions. Standard heavy ions radiation tests employ ion cocktails with energy of the order of 10 MeV per nucleon and with a linear energy transfer ranging from a few MeV cm(2) mg(-1) to hundreds of MeV cm(2) mg(-1). In space, cosmic rays show significant fluxes at energies up to the order of GeV per nucleon. The present work aims at investigating single event damage due to low-, high- and very-high-energy ions. The European Space Agency reference single event upset monitor data are used to support the discussion. Finally, the effect of ionization induced directly by primary particles and ionization induced by recoils produced in an electronic device is investigated for different types of devices.

Development and characterization of DNA microsatellite primers for buriti (Mauritia flexuosa L.f.).

Mauritia flexuosa L. (Arecaceae) is a palm tree species known as buriti that occurs in the Cerrado biome. It is characteristic of the vereda, a typical ecosystem of central Brazil. In this phytophysiognomy, M. flexuosa and other groups of arboreal-herbaceous species develop in open fields with very humid soils. M. flexuosa can be found in forest borders and is a palm tree with a wide distribution in South America (Brazil, Colombia, Venezuela, French Guyana Ecuador, Peru, and Bolivia). The main objectives of this study were to develop simple sequence repeat marker-enriched libraries and to characterize these loci in buriti palm to facilitate future population studies. A total of 40 sequences derived from the microsatellite-enriched libraries were selected for primer design. The optimization results showed that 9 primer pairs could successfully amplify polymorphic target fragments of the expected sizes. The data also show that the described primers can be used in population genetic studies in M. flexuosa to obtain information that will inform conservation and management strategies.

I know your face but can't remember your name: Age-related differences in the FNAME-12NL.

OBJECTIVE: The Face-Name Associative Memory test (FNAME) has recently received attention as a test for early diagnosis of Alzheimer's disease. So far, however, there has been no systematic investigation of the effects of aging. Here, we aimed to assess the extent to which the FNAME performance is modulated by normal ageing. METHOD: In a first step, we adapted the FNAME material to the Dutch population. In a second step, younger (n = 29) and older adults (n = 29) were compared on recall and recognition performance. RESULTS: Significant age effects on name recall were observed after the first exposure of new face-name pairs: younger adults remembered eight, whereas older adults remembered a mean of four out of twelve names. Although both age groups increased the number of recalled names with repeated face-name exposure, older adults did not catch up with the performance of the younger adults, and the age-effects remained stable. Despite of that, both age groups maintained their performance after a 30-min delay. Considering recognition, no age differences were demonstrated, and both age groups succeeded in the recognition of previously shown faces and names when presented along with distractors. CONCLUSIONS: This study presents for the first time the results of different age groups regarding cross-modal associative memory performance on the FNAME. The recall age effects support the hypothesis of age-related differences in associative memory. To use the FNAME as an early cognitive biomarker, further subscales are suggested to increase sensitivity and specificity in the clinical context.

Resonance Raman enhancement by the intralayer and interlayer electron-phonon processes in twisted bilayer graphene.

Twisted bilayer graphene is a fascinating system due to the possibility of tuning the electronic and optical properties by controlling the twisting angle [Formula: see text] between the layers. The coupling between the Dirac cones of the two graphene layers gives rise to van Hove singularities (vHs) in the density of electronic states, whose energies vary with [Formula: see text]. Raman spectroscopy is a fundamental tool to study twisted bilayer graphene (TBG) systems since the Raman response is hugely enhanced when the photons are in resonance with transition between vHs and new peaks appear in the Raman spectra due to phonons within the interior of the Brillouin zone of graphene that are activated by the Moiré superlattice. It was recently shown that these new peaks can be activated by the intralayer and the interlayer electron-phonon processes. In this work we study how each one of these processes enhances the intensities of the peaks coming from the acoustic and optical phonon branches of graphene. Resonance Raman measurements, performed in many different TBG samples with [Formula: see text] between [Formula: see text] and [Formula: see text] and using several different laser excitation energies in the near-infrared (NIR) and visible ranges (1.39-2.71 eV), reveal the distinct enhancement of the different phonons of graphene by the intralayer and interlayer processes. Experimental results are nicely explained by theoretical calculations of the double-resonance Raman intensity in graphene by imposing the momentum conservation rules for the intralayer and the interlayer electron-phonon resonant conditions in TBGs. Our results show that the resonant enhancement of the Raman response in all cases is affected by the quantum interference effect and the symmetry requirements of the double resonance Raman process in graphene.

Synthesis, electronic structure, and Raman scattering of phosphorus-doped single-wall carbon nanotubes.

Substitutional phosphorus doping in single-wall carbon nanotubes (SWNTs) is investigated by density functional theory and resonance Raman spectroscopy. Electronic structure calculations predict charge localization on the phosphorus atom, generating nondispersive valence and conduction bands close to the Fermi level. Besides confirming sustitutional doping, accurate analysis of electron and phonon renormalization effects in the double-resonance Raman process elucidates the different nature of the phosphorus donor doping (localized) when compared to nitrogen substitutional doping (nonlocalized) in SWNTs.

A new family of small (4kDa) neurotoxins from the venoms of spiders of the genus Phoneutria.

A family of 4kDa neurotoxic peptides was purified from venoms of Phoneutria spiders. All have six cysteine residues, and low similarity with other neurotoxins. Three toxins caused moderate inhibition of L-type Ca(2+) channels. The structure of toxin PRTx27C3 was modeled and compared with toxin ADO1. The importance of four residues is suggested.

Intralayer and interlayer electron-phonon interactions in twisted graphene heterostructures.

The understanding of interactions between electrons and phonons in atomically thin heterostructures is crucial for the engineering of novel two-dimensional devices. Electron-phonon (el-ph) interactions in layered materials can occur involving electrons in the same layer or in different layers. Here we report on the possibility of distinguishing intralayer and interlayer el-ph interactions in samples of twisted bilayer graphene and of probing the intralayer process in graphene/h-BN by using Raman spectroscopy. In the intralayer process, the el-ph scattering occurs in a single graphene layer and the other layer (graphene or h-BN) imposes a periodic potential that backscatters the excited electron, whereas for the interlayer process the el-ph scattering occurs between states in the Dirac cones of adjacent graphene layers. Our methodology of using Raman spectroscopy to probe different types of el-ph interactions can be extended to study any kind of graphene-based heterostructure.

Mediastinal tuberculous lymphadenitis presenting as an esophageal intramural tumor: a very rare but important cause for dysphagia.

Dysphagia associated with esophageal mechanical obstruction is usually related to malignant esophageal diseases. Benign lesions are rarely a cause for this type of dysphagia, and usually occur either as an intramural tumor or as an extrinsic compression. Mediastinal tuberculous lymphadenitis is rare in adults, and even more rarely causes dysphagia. We report two cases of dysphagia in adult patients caused by mediastinal tuberculous lymphadenitis, presenting radiologically and endoscopically as an esophageal submucosal tumor. Based on the clinical and imaging diagnosis, the patients underwent a right thoracotomy, and excision of the mass attached to and compressing the esophagus. Pathological examination of the specimens showed a chronic granulomatous inflammation with caseous necrosis, which was consistent with tuberculous lymphadenitis.

Decarboxylation of oxidized single-wall carbon nanotubes.

A classical protocol widely used in organic chemistry of aromatic and polyaromatic molecules has been successfully applied in this work for the decarboxylation of oxidized single-wall carbon nanotube (SWNT) to rend C-H SWNT derivatives. SWNT produced by arc discharge method have been oxidized during a purification process using strongly oxidant agents, such as hydrogen peroxide and nitric acid. The decarboxylation of oxidized SWNT has been conduced with copper(I) oxide in a 50:50 solution of N-methylpyrrolidone and quinoline. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and acid-base potentiometric titration analyses were carried out to characterize quali and quantitatively the changes in the chemical environment on the SWNT surface in each step of the purification and the decarboxylation process. Those techniques showed the appearance of mainly carboxylic and phenolic groups after the purification process and the disappearance of the carboxylic groups after the decarboxylation reaction. Fourier transform infrared spectroscopy analysis indicated also the formation of aliphatic and aromatic C-H groups. X-ray photoelectron spectroscopy and potentiometric titration results determined an efficiency higher than 90% for our decarboxylation procedure. The purity and structural quality of the SWNT sample used in the decarboxylation process were evaluated by thermogravimetry and Raman spectroscopy. Thermogravimetric analysis identified a purified sample with approximately 80 wt% of SWNT, in fractions distributed in highly structured SWNTs (25 wt%), with distribution in composition, length and structural quality (35 wt%) and with very defective and short tubes (25 wt%). The damages on the purified SWNT walls were characterized by the Raman scattering analysis.

Survival and preference of cotton boll weevil adults for alternative food sources.

Plants that have potential as alternative food source (floral nectar, pollen and plant tissues) to the boll weevil during the intercropping season were evaluated considering the prevalent conditions of Cerrado in the Central Brazil. Initially, we tested the nutritional adequacy for the survival of the insect of flower resource (pollen and nectar) provided by eight plant species (fennel, mexican sunflower, castor bean, okra, hibiscus, sorghum, pigeonpea and sunn hemp). Subsequently, we tested if the resources provided by the selected plants continued to be exploited by the boll weevil in the presence of cotton plant, its main food source average longevity of boll weevil adults was significantly longer when they were fed on hibiscus' flowers (166.6 ± 74.4) and okra flowers (34.7 ± 28.9) than when they fed on flowers of other six species. Subsequently, the preference of the boll weevil in the use of resources was compared between okra or hibiscus and cotton plants, in dual choice experiments. Boll weevils preferred plants of the three species in the reproductive stages than those in vegetative stages. Although the cotton plant in the reproductive stage was the most preferred plant of all, boll weevils preferred flowering okra and hibiscus than cotton at the vegetative stage.

Edge phonons in black phosphorus.

Black phosphorus has recently emerged as a new layered crystal that, due to its peculiar and anisotropic crystalline and electronic band structures, may have important applications in electronics, optoelectronics and photonics. Despite the fact that the edges of layered crystals host a range of singular properties whose characterization and exploitation are of utmost importance for device development, the edges of black phosphorus remain poorly characterized. In this work, the atomic structure and behaviour of phonons near different black phosphorus edges are experimentally and theoretically studied using Raman spectroscopy and density functional theory calculations. Polarized Raman results show the appearance of new modes at the edges of the sample, and their spectra depend on the atomic structure of the edges (zigzag or armchair). Theoretical simulations confirm that the new modes are due to edge phonon states that are forbidden in the bulk, and originated from the lattice termination rearrangements.

Leaf beetle (Chrysomelidae: Coleoptera) assemblages in a mosaic of natural and altered areas in the Brazilian cerrado.

In landscape mosaics, species may use different vegetation types or be restricted to a single vegetation type or land-use feature highlighting the importance of the interaction of species requirements and environmental heterogeneity. In these systems, the determination of the overall pattern of ß-diversity can indicate the importance of the environmental heterogeneity on diversity patterns. Here, we evaluate leaf beetles (Coleoptera: Chrysomelidae) as habitat quality bioindicators in a system with varying intensities of human impacts and different phyto-physiognomies (from open field to forests). We collected 1117 leaf beetles belonging to 245 species, of which 12 species and 5 genus were considered possible bioindicators based on IndVal measures. Higher species richness was observed in forests and regenerating fields, and habitats with lower species richness included pastures, mines, and veredas. Natural fields, regenerating fields, natural cerrado, and forest had higher values of ß-diversity. Bioindicator systems that include not only species richness and abundance but also assemblage composition are needed to allow for a better understanding of Chrysomelidae response to environmental disturbance.

Relaxin affects cell organization and early and late stages of spermatogenesis in a coculture of rat testicular cells.

Relaxin and its receptor RXFP1 are co-expressed in Sertoli cells, and relaxin can stimulate proliferation of Sertoli cells. In this study, we investigated a role of relaxin in spermatogenesis, using a short-term culture of testicular cells of the rat that allowed differentiation of spermatogonia to spermatids. Sertoli, germ, and peritubular myoid cells were the predominant cell types in the culture. Sertoli and germ cells expressed RXFP1. Cultures were incubated without (control) or with 0.5% fetal bovine serum (FBS) or 100 ng/mL H2 relaxin (RLN) for 2 days. Cell organization, number, and differentiation were analyzed after 2 (D2), 5 (D5) or 8 (D8) days of culturing. Although the proportion of germ cells decayed from D2 to D5, the relative contribution of HC, 1C, 2C, and 4C germ cell populations remained constant in the control group during the whole culture. RLN did not affect the proportion of germ cell populations compared with control, but increased gene and/or protein expression of the undifferentiated and differentiated spermatogonia markers PLZF and c-KIT, and of the post-meiotic marker Odf2 in D5. RLN favored organization of cells in tubule-like structures, the arrangement of myoid cells around the tubules, arrangement of c-KIT-positive spermatogonia at the basal region of the tubules, and expression of the cell junction protein ß-catenin close to the plasma membrane region. Knockdown of relaxin with small interfering RNA (siRNA) reduced expression of ß-catenin at the cell junctions, and shifted its expression to the nucleus. We propose that relaxin may affect spermatogenesis by modulating spermatogonial self renewal and favoring cell contact.

Developmental changes in the constitutive and inducible expression of cytochrome P450 3A2.

Using a CYP3A2-specific oligonucleotide and an antipeptide antibody raised against the C terminus of CYP3A2 (VINGA) it is demonstrated that metyrapone administration to adult (12 weeks old) but not immature (3 weeks old) male Sprague Dawley rats induces the hepatic expression of CYP3A2 mRNA and protein. The constitutively expressed level of CYP3A2 protein in adult male rats is markedly lower than the levels expressed in immature rats as determined using the anti-VINGA antibody, in contrast to previous reports using antibodies that do not discriminate between CYP3A forms. Hepatic microsomal CYP3A2 protein expression, examined between 3 and 15 weeks of age, is extinguished between 9 and 12 weeks of age in contrast to immunoreactive CYP3A protein (determined using a nonselective antibody) and CYP3A-dependent androstenedione 6beta-hydroxylase activity. These data suggest that the regulation of the induction of CYP3A2 is developmentally controlled and that the major expressed adult form(s) of constitutively expressed CYP3A is not CYP3A2.