A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Standardization of a rapid quadruplex PCR method for the simultaneous detection of bovine, buffalo, Salmonella spp, and Listeria monocytogenes DNA in milk / [Padronização de um método rápido de PCR quadriplex para a detecção simultânea de DNA de bovino, bubalino, Salmonella spp. e Listeria monocytogenes em leite]

The objective of the present study was to Standardize a Polymerase Chain Reaction (PCR) protocol for the authentication of bovine and buffalo milk, and to detect the presence of Salmonella spp. and Listeria monocytogenes. For this, the target DNA was extracted, mixed, and subjected to a PCR assay. Milk samples were defrauded and experimentally contaminated with microorganisms to assess the detection of target DNA at different times of cultivation, bacterial titers, and concentration of genetic material. In addition, the protocol was tested with DNA extracted directly from food, without a pre-enrichment step. The proposed quadruplex PCR showed good accuracy in identifying target DNA sequences. It was possible to simultaneously identify all DNA sequences at the time of inoculation (0h), when the samples were contaminated with 2 CFU/250mL and with 6h of culture when the initial inoculum was 1 CFU/250mL. It was also possible to directly detect DNA sequences from the food when it was inoculated with 3 CFU/mL bacteria. Thus, the proposed methodology showed satisfactory performance, optimization of the analysis time, and a potential for the detection of microorganisms at low titers, which can be used for the detection of fraud and contamination.

O objetivo do presente estudo foi padronizar um protocolo de reação em cadeia da polimerase (PCR) para a autenticação de leite bovino e bubalino e a detecção da presença de Salmonella spp. e Listeria monocytogenes. Para isso, o DNA-alvo foi extraído, misturado e submetido ao ensaio de PCR. Amostras de leite foram fraudadas e contaminadas experimentalmente com os micro-organismos, para se avaliar a detecção do DNA-alvo em diferentes tempos de cultivo, os títulos bacterianos e a concentração de material genético. Além disso, o protocolo foi testado com DNA extraído diretamente do alimento, sem a etapa de pré-enriquecimento. A PCR quadriplex proposta mostrou boa precisão na identificação de sequências de DNA-alvo. Foi possível identificar simultaneamente todas as sequências de DNA no momento da inoculação (0h), quando as amostras estavam contaminadas com 2 UFC/250mL, e com seis horas de cultura, quando o inóculo inicial foi de 1 UFC/250mL. Também foi possível detectar diretamente as sequências de DNA do alimento quando este foi inoculado com 3 UFC/mL de bactérias. Dessa forma, a metodologia proposta apresentou desempenho satisfatório, otimização do tempo de análise e potencial para detecção de micro-organismos em baixos títulos, podendo ser utilizada para detecção de fraude e contaminação.

Padronização de uma PCR para a autenticação do Salmo salar em pratos da culinária japonesa / Standardization of a PCR for the authentication of Salmo salar in dishes of Japanese cuisine

O objetivo deste trabalho foi padronizar uma PCR para a detecção do Salmo salar, a qual possa ser usada na autenticação do salmão utilizado em pratos da culinária japonesa e do pescado comercializado in natura. Para isso, dois lotes de sushi foram produzidos experimentalmente. Além disso, foram visitados 38 estabelecimentos que comercializam comida japonesa e 10 peixarias na região metropolitana de Belém, visando à coleta do sushi, do temaki e do pescado pertencente à espécie Salmo salar. Os dados demonstraram que a técnica foi eficiente para a autenticação de Salmo salar, visto que a espécie foi detectada tanto nas amostras de sushis preparados experimentalmente quanto nas alíquotas de pescados isolados, utilizados para a preparação do sushi. Em contrapartida, a espécie Salmo trutta não foi detectada nas amostras de sushis preparados com esta espécie nem nas alíquotas de pescado isolado. Além disso, foi possível a confirmação da utilização da espécie Salmo salar no preparo das amostras de sushi, temaki e de pescado. Portanto, concluiu-se que a técnica foi capaz de amplificar o DNA da referida espécie e não gerou identificação inespecífica quando a espécie Salmo trutta foi analisada, podendo ser uma ferramenta adequada para a autenticação do Salmo salar.(AU)

The objective of this work was to standardize a PCR for the detection of Salmo salar, which can be used in the authentication of salmon used in Japanese dishes and fish commercialized in natura. For this, two batches of sushi were produced experimentally. In addition, 38 establishments that sell Japanese food and 10 fishmongers in the metropolitan area of Belém were visited, aiming to collect sushi, temaki and fish belonging to the species Salmo salar. The data demonstrated that the technique was efficient for the authentication of Salmo salar, since the species was detected in both the experimentally prepared sushi samples and the isolated fish aliquots used for the preparation of sushi. In contrast, the species Salmo trutta was not detected in the sushi samples prepared with this species nor in the isolated fish aliquots. In addition, it was possible to confirm the use of the Salmo salar species in the preparation of sushi, temaki and fish samples. Therefore, it was concluded that the technique was able to amplify the DNA of this species and did not generate nonspecific identification when the species Salmo trutta was analyzed, being able to be a suitable tool for the authentication of Salmo salar.(AU)

Participants' perspectives of weekly telephonic mood monitoring in South Africa: a feasibility study.

BACKGROUND: Mood and anxiety disorders have a high lifetime prevalence, and their chronicity adds to the management burden of already scarce and strained mental health care resources, particularly in developing countries. Non-professional-assisted interventions and technology (such as weekly telephonic mood monitoring) could assist in the early identification of symptoms of relapse and hospitalization prevention. The present study aimed to determine participants' perspectives and the feasibility of weekly telephonic mood monitoring in order to inform the development of the full study. METHOD: Semi-structured telephonic interviews (n = 37; 89.2% female; mean age = 33.1 years) were conducted as part of the full-scale feasibility study (N = 61; named the Bipolar Disorder Mood Monitoring (BDMM) Study). The BDMM Study was conducted to determine the viability of weekly telephonic mood monitoring, spanning 26 weeks and starting 1 week post-discharge. Frequency and descriptive statistical analyses (using SPSS version 24) were undertaken, and qualitative data were analyzed using thematic content analysis. RESULTS: This article presents the findings from the semi-structured interview section of the BDMM Study. Participants generally expressed positive experiences and perceptions of weekly telephonic mood monitoring, stating that they would advise others to also take part in weekly telephonic mood monitoring. Nonetheless, some participants did make suggestions for improvement of mood monitoring while others expressed negative experiences of weekly telephonic mood monitoring. CONCLUSION: The results of the semi-structured interviews of the BDMM Study indicated that participants perceived weekly telephonic mood monitoring to be helpful in lightening the burden of mood and anxiety disorders (e.g., having someone to talk to, providing insight into their disorders). Not only did it help them, but they also perceived mood monitoring to be potentially helpful to future participants. However, weekly mood monitoring was also burdensome in itself (including being too time consuming and having to answer questions when feeling down). Importantly, the findings highlighted that participants' and researchers' perceptions and experiences may not be congruent (especially in terms of therapeutic misconception). The current findings may inform researchers' future approach to study design and participant relationships.

Saccharomyces boulardii modulates and improves the immune response to Bovine Herpesvirus type 5 Vaccine / Saccharomyces boulardii modula e melhora a resposta imune de vacina contra o Herpes bovino tipo 5

There have been significant efforts towards the development of more efficient vaccines for animal health. A strategy that may be used to improve vaccine efficacy is the use of probiotics to enhance the immune response of the host, leading to increased immunogenicity of antigen preparations. Bovine herpesvirus 5 (BoHV-5) is an example of an important animal pathogen for which vaccines have provided only limited protection. In this study, we examined the use of the probiotic Saccharomyces boulardii (Sb) as a potential adjuvant to improve vaccine efficiency. We found that the supplemented animals exhibited an enhanced systemic IgG antibody response toward a Th1 response in favor of IgG2a and increased mRNA expression levels of the cytokines IFN-y, IL-12, IL-17 and IL-10 in the spleen. These results suggest that Sb supplementation may provide a promising means for improving the efficiency of vaccines, particularly those that rely on a cell-mediated immune response.(AU)

Esforços significativos têm sido realizados para o desenvolvimento de vacinas mais eficientes em saúde animal. Uma estratégia que pode ser usado para melhorar a eficácia da vacina é o uso de probióticos para melhorar a resposta imune do hospedeiro, conduzindo ao aumento da imunogenicidade de preparações de antígenos. Herpesvírus bovino 5 (BoHV-5) é um exemplo de um importante patógeno animal para os quais vacinas têm fornecido apenas uma protecção limitada. Neste estudo, examinou-se o uso do probiótico Saccharomyces boulardii (Sb) como um adjuvante potencial para melhorar a eficiência da vacina. Verificou-se que os animais suplementados apresentaram uma produção de anticorpos IgG superior e com desvio para Th1 em favor de IgG2, além do aumento dos níveis de expressão de mRNA para as citocinas IFN-γ, IL-12, IL-17 e IL-10. Esses resultados sugerem que a suplementação de Sb pode fornecer um meio promissor para melhorar a eficiência de vacinas, particularmente aquelas que dependem de uma resposta imune mediada por células.(AU)

The use of quorum sensing to improve vaccine immune response.

Enterotoxigenic Escherichia coli (ETEC) infection is an important cause of diarrhea in both newborn and post-weaning pigs, it is also responsible for economic losses on farms worldwide. Vaccines that use ETEC virulence factors have been well documented, and several vaccines containing inactivated bacteria with protective antigens, or purified (isolated) antigens are available on the market. Vaccination of pregnant sows is widely seen as an effective strategy for the control of the disease. Yet these vaccines very often do not lead to efficient protection. In this study, we produced an ETEC bacterin with the use of quorum sensing (QS), and observed a significant expression of F4 adhesin, and heat-labile toxin (LT) in the cultures when compared to the controls. Mice, and pigs vaccinated with the QS bacterin demonstrated higher antibody titers against these antigens when compared with commercial and control bacterin. Our results suggest that the system might bring promising improvements in ETEC bacterin efficacy.

Workshop on laboratory protocol standards for the Molecular Methods Database.

Management of data to produce scientific knowledge is a key challenge for biological research in the 21st century. Emerging high-throughput technologies allow life science researchers to produce big data at speeds and in amounts that were unthinkable just a few years ago. This places high demands on all aspects of the workflow: from data capture (including the experimental constraints of the experiment), analysis and preservation, to peer-reviewed publication of results. Failure to recognise the issues at each level can lead to serious conflicts and mistakes; research may then be compromised as a result of the publication of non-coherent protocols, or the misinterpretation of published data. In this report, we present the results from a workshop that was organised to create an ontological data-modelling framework for Laboratory Protocol Standards for the Molecular Methods Database (MolMeth). The workshop provided a set of short- and long-term goals for the MolMeth database, the most important being the decision to use the established EXACT description of biomedical ontologies as a starting point.

[Multimodal therapy of children with attention deficit/hyperactivity disorder and their parents in in-patient rehabilitation]. / Multimodales Therapiekonzept für Kinder mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen und deren Begleitperson in der stationären Rehabilitation.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent psychic disorders of childhood, characterized by high persistence and an increased risk for the development of externalising disorders of behavior. Due to ADHD increased problems can be frequently observed at school as well as in the social and emotional context of the child. Concepts for in-patient rehabilitation have not been developed, although effective modifications of the behavior of ADHD patients appeared to be achievable under the conditions found in in-patient rehabilitation. OBJECTIVE: The present pilot study aimed to evaluate whether this newly developed concept has any benefit on psychological problems, coping and quality of life. METHOD: In total, n = 28 boys with ADHD 7 to 12 years old were included into a quasi-experimental pre-post design and completed self-report questionnaires on psychological problems, coping and quality of life. In addition, 26 mothers evaluated the behavior problems, psychological problems and quality of life of their sons at the beginning and the end of in-patient rehabilitation. During a 4-week in-patient rehabilitation all children and their mothers took part in a multimodal training containing components of behavior therapy and cognitive-behavioral therapy (self-instruction, self-management, and stress management), applied in child-, parent-child- and parent-centered interventions. RESULTS: Parents estimated the behavior problems of their children as significantly reduced after in-patient rehabilitation as compared to before. In addition, psychological problems and quality of life improved significantly in self- and parent-proxy reports during the in-patient rehabilitation. CONCLUSION: Our results support the hypothesis that this multimodal therapy concept is an effective tool for the treatment of ADHD patients. However, a replication of our results in a control-group study on a larger population is required.

Avaliação microbiológica de queijo colonial produzido na cidade de Três Passos, RS / Microbiological evaluation of produced cheese in the city of Três Passos, RS

Vinte e cinco amostras de queijo colonial, oriundas de cinco estabelecimentos da cidade de Três Passos, RS, foram submetidas às seguintes análises microbiológicas: contagens de bactérias mesófilas, bactérias psicrotróficas, coliformes totais, coliformes fecais e pesquisa de Salmonella. As médias das contagens de microorganismos mesófilos e psicrotróficos foram, na propriedade A, 4,3 x 10 UFC/g e 1,4 x 10 UFC/g; na B, 3,7 x 10 UFC/g e 4,4 x 10 UFC/g; na C, 2,5 x 10 UFC/g e 2,8 x 10 UFC/g; na D, 1,4 x 10 UFC/ g e 4,0 x 10 UFC/g e, na E, 1,5 x 10 UFC/g e 6,7 x 10 UFC/g, respectivamente. As contagens de coliformes totais nas propriedades A, B, C e D foram > 110 NMP/g e na propriedade E 88,9 NMP. Os resultados das contagens coliformes fecais foram 47,5 NMP/g na propriedade A, >110 NMP/g na B,2,1 NMP/g na C, <0,3 NMP/g na D e 10,0 NMP/g na E. A pesquisa de Salmonella apresentou ausência / 25g em todas as amostras. Os resultados revelaram altos índices de microorganismos nos produtos, sugerindo qualidade de matéria prima insatisfatória e/ou condições de produção e armazenamento inadequadas.

Case reports: tinea corporis in a 13-year-old German girl due to Trichophyton schoenleinii.

We report the first case of a tinea corporis with partly profound lesions in a 13-year-old girl on her arms, legs and trunk due to Trichophyton schoenleinii but without any lesion on scalp and hair. Moreover, this is the first case of an infection with Trichophyton schoenleinii in Germany since more than 40 years. The diagnosis was confirmed by microscopy of mycological specimens. Other causes of the skin symptoms could be excluded (atopic dermatitis, bacterial or other fungal infection). Clinical and epidemiological aspects of this anthropophile dermatophyte are briefly reviewed.

Histerectomía total laparoscópica: resultados en 3 años de desarrollo de la técnica utilizando el manipulador uterino de Clermont Ferrand / Laparoscopic hysterectomy during a period of 3 years using the intrauterine manipulator Clermont Ferrand

Damos a conocer una casuística de histerectomía total laparoscópica en un período de 3 años utilizando el manipulador uterino de Clermont Ferrand; se analizan los resultados, seguimiento y complicaciones.

An improved and rapid method to construct skin equivalents from human hair follicles and fibroblasts.

To produce sufficient amounts of high quality skin equivalents (SE), either allogenic for dermatopharmacological and dermatotoxicological studies or autologous for transplantation purposes, we established a rapid, easy and cost effective three-dimensional SE model on the basis of human dermal fibroblasts, collagen and freshly plucked hair follicles. Acidic liquid collagen was polymerized with sodium hydroxide in the presence of fibroblasts to form a dermal equivalent (DE) resembling normal human dermis. At 24 h later, freshly plucked hair follicles were implanted into the surface of these DEs after cutting their bulbs off. Another 48 h later, the surface of the SEs was lifted to the air-liquid interface. Fourteen days after implantation, outgrowing keratinocytes from the outer root sheath of the hair follicles completely covered the surface of the SE and built a fully developed, multi-layered and cornified epidermis. Histology and immunofluorescence studies with specific antibodies directed against components of keratinocytes, fibroblasts, cell-adhesion molecules, different extracellular matrix and basement membrane proteins revealed the similarity of our three-dimensional SEs to the in vivo situation in normal human skin. Using autologous cell sources and cell culture media enriched with serum from the respective cell donor, it will be possible to use these SEs for autologous transplantation, thereby reducing the risk of transplant rejection.

Indecisive M13 procoat protein mutants bind to SecA but do not activate the translocation ATPase.

The M13 procoat protein serves as the paradigm for the Sec-independent membrane insertion pathway. This protein is inserted into the inner membrane of Escherichia coli with two hydrophobic regions and a central periplasmic loop region of 20 amino acid residues. Extension of the periplasmic loop region renders M13 procoat membrane insertion Sec-dependent. Loop regions with 118 or more residues required SecA and SecYEG and were efficiently translocated in vivo. Two mutants having loop regions of 80 and 100 residues, respectively, interacted with SecA but failed to activate the membrane translocation ATPase of SecA in vitro. Similarly, a procoat mutant with two additional glutamyl residues in the loop region showed binding to SecA but did not stimulate the ATPase. The three mutants were also defective for precursor-stimulated binding of SecA to the membrane surface. Remarkably, the mutant proteins act as competitive inhibitors of the Sec translocase. This suggests that the region to be translocated is sensed by SecA but the activation of the SecA translocation ATPase is only successful for substrates with a minimum length of the translocated region.

Pharmacotherapy of ectoparasitic infections.

Epizoonoses such as scabies, lice and cimicosis are common, vexing disorders that occur worldwide. Historically, many treatment modalities have been employed in the management of these disorders, and most of the drugs described in this review are of historical interest and no longer recommended or in widespread use because of their wide spectrum of adverse effects. More recently, reports documenting resistance against various antiectoparasite drugs, complicated and severe courses of the diseases, and adverse effects of drug therapy have prompted the development of new treatment strategies and drugs for optimal disease management. Because the strategies currently recommended for the treatment of ectoparasites differ worldwide, this review proposes a rational approach to selecting the best therapeutic agent by comparing the pharmacokinetics, pharmacodynamics, drug efficacy and adverse effects. A literature search of the currently Internet accessible libraries PubMed, Medline and Ideal library, of citations of articles found there, and from communications with the Federal Institute for Drugs and Medical Devices, Germany, was conducted based on this approach. One major observation of this literature search is that permethrin is the treatment of choice for lice and scabies in the US and in Great Britain, whereas lindane is still recommended for scabies in most other European countries because of its longer-standing record of effectiveness. Although permethrin has not yet been proven to be more effective than lindane in treating infections with these ectoparasites, it currently appears to have the best efficacy versus safety profile of topical treatments for scabies and lice. Ivermectin is a newer oral drug for the treatment of ectoparasites, which has been used with great success in the treatment of onchocercosis and other endoparasites. Although ivermectin appears to be a promising drug, its role in the treatment of ectoparasitic infections will be clarified as more study data become available. Finally, it is important to emphasise the clinical aspects of ectoparasite therapy and that providing the patient with optimal instructions on the use of topical therapeutics is of great importance in avoiding adverse effects and assuring complete removal of the ectoparasite, thereby avoiding the development of drug-resistance.

Biodisponibilidad y absorción de progesterona micronizada por vía oral en mujeres fértiles con dosis única diaria / Bioavailability and absorption of oral micronized progesterone in fertile women using daily single dose

La administración de progesterona por vía oral ha estado limitada por su pobre absorción y la rápida metabolización en intestino e hígado. Con el fin de superar los problemas de absorción de la progesterona oral y los defectos metabólicos adversos de los progestágenos sintéticos se han desarrollado diferentes presentaciones de progesterona micronizada en combinación con vehículos lipofílicos. La reducción del tamaño de la particulas mediante la micronización aumenta su disolución y al combinar la progesterona con vehículos lipofílicos se incrementa su biodisponibilidad. Nuestro objetivo fue estudiar la absorción y biodisponibilidad de una nueva formulación de progesterona micronizada, recientemente incorporada al mercado en nuestro país (Progendo©). Participan 15 mujeres voluntarias, en edad fértil y en fase folicular del ciclo menstrual. Se formaran dos grupos: a 10 mujeres se les administró 200 mg de progesterona micronizada en una dosis única matinal y a 5 se les administró cápsulas conteniendo placebo. Se midieron los niveles séricos de progesterona (Cmáx) alcanzó a 22,6ñ10,5 ng/ml (rango 8,0 a 74 ng/ml) y el tiempo máximo (Tmáx) fue de 2,5 ñ 0,84 horas. El área bajo la curva (AUC 0-8) fue de 71,4 ng*hr/mL durante las 8 primeras horas. Los niveles de progesterona plasmática fueron significativamente superiores al grupo control desde la primera hora, y retomaron a valores basales después de 24 horas. Los niveles de 17 OH progesterona mostraron una tendencia similar con un tiempo máximo de 2,6 ñ 0,6 horas, una Cmáx. de 0,92 ñ 0,38 ng/ml (rangos de 0,5 a 1,3 ng/ml). El AUC 0-8 de 17 hidroxiprogesterona fue 3,93. La absorción y biodisponibilidad de esta nueva formulación de progesterona micronizada alcanza niveles plasmáticos homologables a los presentados en fase lútea en mujeres cíclicas normales

13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors.

Despite its potent biologic effect on human sebocytes, 13-cis retinoic acid exhibits low binding affinity for cellular retinoic acid binding proteins and nuclear retinoid receptors. Hence, 13-cis retinoic acid may represent a pro-drug possibly acting through all-trans isomerization. In this study, marked isomerization of 13-cis retinoic acid has been confirmed in cultured SZ95 sebocytes showing 2- to 15-fold higher levels of all-trans retinoic acid at 12-72 h, as measured by high performance liquid chromatography. In contrast, only low amounts of all-trans retinoic acid were converted intracellularly to its 13-cis isoform. 9-cis retinoic acid was not detected after either 13-cis retinoic acid or all-trans retinoic acid treatment. The rapid isomerization of 13-cis retinoic acid to high levels of all-trans retinoic acid was a sebocyte-specific event, as no significant isomerization of 13-cis retinoic acid to all-trans retinoic acid occurred in HaCaT keratinocytes. De novo mRNA expression of cytochrome P450 1A1, a major xenobiotic metabolizing enzyme, in SZ95 sebocytes was induced by all-trans retinoic acid, but not by 13-cis retinoic acid. In addition, mRNA levels of cellular retinoic acid-binding protein II, which is supposed to regulate the concentration of intracellular all-trans retinoic acid, rapidly increased under all-trans retinoic acid treatment (30 min-6 h), whereas the 13-cis retinoic acid effect was markedly weaker and delayed. Both 13-cis retinoic acid and all-trans retinoic acid suppressed mRNA expression of cytochrome P450 1A2. In parallel experiments, 13-cis retinoic acid significantly reduced SZ95 sebocyte proliferation at 10-7 M, show- ing 30-40% inhibition after 9 d. All-trans retinoic acid and 9-cis retinoic acid exhibited similar anti-proliferative effects. AGN 193109, a pan-antagonist of the retinoic acid receptors, antagonized the anti-proliferative activity of all retinoic acid isomers tested in a concentration-dependent manner with complete abolishment at ratios of 1:10 13-cis retinoic acid and 1:1 all-trans retinoic acid. Coincubation of SZ95 sebocytes with 13-cis retinoic acid and AGN 193109 did not alter the intracellular concentration of 13-cis retinoic acid and its isomerization profile. In contrast, the retinoid X receptor antagonist CD 3507 did not affect the inhibition of SZ95 sebocyte proliferation induced by retinoic acids. Our findings indicate: (i) a selective 13-cis retinoic acid isomerization to all-trans retinoic acid in the intracellular compartment of SZ95 sebocytes; (ii) a reduced all-trans retinoic acid inactivation process after 13-cis retinoic acid treatment as compared with treatment with all-trans retinoic acid; and (iii) a retinoic acid receptor-mediated inhibition of SZ95 sebocyte proliferation. These data explain the sebocyte-specific activity of 13-cis retinoic acid and support a pro-drug/drug relation between 13-cis retinoic acid and all-trans retinoic acid.