Environmental factors may contribute to autism development and male bias: Effects of fragrances on developing neurons.

BACKGROUND: Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, impairments in verbal and nonverbal communication, and stereotyped patterns of behavior. Previous studies have implicated environmental factors in the development of ASD. Although no reliable neurophysiological network is associated with ASD, low levels of plasma oxytocin (OXY) and arginine vasopressin (AVP) have been reported. The "twin" nonapeptides OXY and AVP are mainly produced in the brain of mammals, and dysregulation of these neuropeptides has been associated with changes in behavior, especially social interactions. METHODS: Previously, we analyzed 91 commonly used fragrances and reported significant mutagenic, neurocytotoxic, and stimulatory effects on fetal neuroblastoma cell lines (NBC). In this study, we analyzed the neuromodifications of three selected fragrances on male and female human fetal brain neurons, utilizing immunohistochemistry. RESULTS: We show that exposure to femtomolar concentrations of fragrances results in morphological changes by light microscopy in the NBC. Importantly, these fragrances significantly reduced the OXY- and AVP-receptor positive (OXYR+ and AVPR+) neurons in male NBC but not in female NBC, possibly contributing to the development of male bias in ASD. CONCLUSION: This study is the first to show a potential link between fragrance exposure, depletion of OXYR+ and AVPR+ neurons, and a male bias in autism.

Bacteriophage therapy: a potential solution for the antibiotic resistance crisis.

The emergence of multiple drug-resistant bacteria has prompted interest in alternatives to conventional antimicrobials. One of the possible replacement options for antibiotics is the use of bacteriophages as antimicrobial agents. Phage therapy is an important alternative to antibiotics in the current era of drug-resistant pathogens. Bacteriophages have played an important role in the expansion of molecular biology and have been used as antibacterial agents since 1966. In this review, we describe a brief history of bacteriophages and clinical studies on their use in bacterial disease prophylaxis and therapy. We discuss the advantages and disadvantages of bacteriophages as therapeutic agents in this regard.

Role of perfumes in pathogenesis of autism.

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents, cosmetics, soap, and a wide variety of commonly used items, even in food flavoring to enhance product taste. Here we provide evidence that a majority of perfumes are highly mutagenic at femtomolar concentrations, and cause significant neuromodulations in human neuroblastoma cells at extremely low levels of concentration, levels that are expected to reach a developing fetal brain if the pregnant mothers are exposed to these chemicals.

Potential utility of GB virus type C as a preventive vaccine for HIV-1.

Recent flurries of literature on the beneficial effects of GB virus type C (GBV-C), a hepatitis C-related virus, in HIV-1 coinfected individuals have raised the possibility of its potential use as a preventive vaccine in people with a high risk for HIV-1. However, these findings are still controversial, and the mechanisms contributing to the apparent beneficial effects of GBV-C are still unresolved. Researchers debate whether the beneficial effects of coinfection of GBV-C in HIV-1-infected individuals are due to GBV-C viremia or rather the presence of GBV-C anti-E2 antibodies. We review the strengths and weaknesses of various aspects of the GBV-C debate and propose a new perspective involving intracellular molecular events that attempts to synthesize numerous contrasting perspectives and ideas, while suggesting new directions for future research in this area.

Of lives and livers: emerging responses to the hepatitis C virus.

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). HCV is an etiological agent of acute and chronic liver disease that exists throughout the world. The high genetic variability of the HCV genome is reflected by six genotypes (1 to 6). Each genotype has a characteristic geographical distribution, which is important epidemiologically. HCV is a blood-borne virus that generally circulates in low titers in the serum of infected individuals. Epidemiologic studies show that the most efficient transmission of HCV is through the transfusion of blood or blood products, the transplantation of organs from infected donors, and the sharing of contaminated needles among injection-drug users. However, fewer than half of patients with acute hepatitis C report a history of such exposure. A small number of epidemiologic studies demonstrate that perinatal, sexual, household, and occupational transmission occurs, but our understanding of the risks of transmission in these settings has been limited. The therapy for chronic hepatitis C has evolved steadily since alpha interferon was first approved for use. At present, the optimal regimen appears to be a 24- or 48-week course of a combined pegylated alpha interferon and ribavirin regimen. Currently, the combination of RNAi (LV-shIRES) with IFN-α has been proposed to prevent therapeutic resistance, and to promote enhanced antiviral activity against HCV. However, any RNAi based therapy may be years away due to off-target effects.

Role of HERV-W syncytin-1 in placentation and maintenance of human pregnancy.

Over half of human genome contains retroelements, including retrotransposons, retroviruses, and other elements. Human endogenous retroviruses (HERVs) comprise about 8% of human genome. The products of 2 of 16 identified genes of HERV-W seem to play a pivotal role in the placentation. These 2 genes are HERV-W env glycoprotein (syncytin-1) and HERV-FRD env glycoprotein (syncytin-2). It has been shown previously that syncytin-1 mediates cell-cell fusions of cytotrophoblasts into syncytiotrophoblasts. In addition, HERV-W env contains an immunosuppressive region that may prevent rejection of a semiallogenic fetus from the mother's immune system. We analyzed 40 full-term placental tissues to localize the expression of syncytin-1-ISR by immunohistochemical staining and by reverse trancscriptase (RT) in situ polymerase chain reaction (PCR). Both the immunostaining and in situ RT-PCR showed strong expression of syncytin-1 in the syncytiotrophoblast layer from the full-term placental tissues. To further analyze the mechanism of early embryo HERV-W env activation, we utilized a HTR-8/SVneo cell line developed from first trimester human trophoblasts and subjected them to various physiologic concentrations of maternal hormones. Quantitative RT-PCR analyses demonstrated that exposure to progesterone significantly upregulated the HERV-W env expression, whereas several other hormones apparently played lesser roles. In conclusion, our findings suggest that expression of syncytin-1 (HERV-W env) in utero is expressed exclusively in the syncytiotrophoblast layer and is upregulated by progesterone.