Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.     

Better health data with a portable microcomputer at the periphery: an anthropometric survey in Cape Verde

A portable microcomputer was programmed to record anthropometric nutritional data from children aged under 7 years in either a clinic or a population survey situation. An alarm sounds when the anthropometric measurements of a child are below a predetermined value; an immediate check thus avoids the need for subsequent data cleaning and discarding of doubtful information. Data cut-off points in the computer can be adjusted to suit the survey or service needs of the situation. A print-out at the end of the clinic session provides immediate feedback for the staff and a record of the nutritional status of the group.     

Risk factors for perinatal death in Cape Verde

Summary.   Risk factors for perinatal death in the Cape Verde islands were assessed among 104 bereaved mothers and 292 mothers of surviving infants in an area-based case–control study in 1992–93. Prospectively gathered information on risk factors was obtained from medical records supplemented with post-partum interviews and anthropometric measurements of mothers and infants. No autopsies were performed. Multiple logistic regression analysis was applied. Out of 23 alleged maternal and two alleged infant risk factors, the following seven proved significantly and independently correlated with perinatal death: first pregnancy (odds ratio [OR] = 2.9); previous hypertensive disease (OR = 4.2); previous perinatal death (OR = 4.6); pre-eclampsia (OR = 7.0); non-cephalic fetal presentation (OR = 17.1); male infant (OR = 2.1) and maternal post-partum fever (OR = 3.1). The perinatal mortality rate was calculated as 37–46/1000 total births. A reduction in the mortality rate warrants antenatal and obstetric care with emphasis on primiparous women; improved detection and treatment of hypertensive disorders and genital infections; and improved intrapartum fetal observation and resuscitation routines.     

Genital infections among antenatal care attendees in Cape Verde

In a cross-sectional study, 350 pregnant Capeverdian women were examined to assess the prevalence of Chlamydia trachomatis infection (CT), Neisseria gonorrhoeae infection (NG) and Bacterial vaginosis (BV). Among various analytic methods used, the polymerase chain reaction PCR (for NG, CT) yielded a higher detection rate than did direct microscopy or culture (NG), or direct immuno-fluorescence (CT). Since the PCR analytic of air-dried specimens is not hampered by harsh storage and transport conditions, it could serve to validate other detection methods where laboratory facilities are suboptimal. Among sociodemographic risk factors young age, and currently living alone, were significantly associated with infection.     

Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular,Cellular, and in Vivo Studies

Background

Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs.

Objective

We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs.

Methods

We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs.

Results

We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC₅₀) ≈ 55 nM; rate inhibition constant (k_inact) = 5 × 10⁴ M⁻¹ · sec⁻¹], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC₅₀ ≈ 1 μM; k_inact = 1 × 10⁴ M⁻¹ · sec⁻¹).

Conclusions

Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences.     

Effect of environmental substances on the activity of arylamine N-acetyltransferases

Arylamine N-acetyltransferases (NAT) are xenobiotic-metabolizing enzymes responsible for the acetylation of many aromatic arylamine and heterocyclic amines, thereby playing an important role in both detoxification and activation of numerous drugs and carcinogens. Two closely related isoforms (NAT1 and NAT2) have been described in humans. NAT2 is mainly expressed in liver and gut, whereas NAT1 is found in a wide range of tissues. Interindividual variations in NAT genes have been shown to be a potential source of pharmacological and/or pathological susceptibility. In addition, there is now evidence that non genetic factors, such as substrate-dependent inhibition, drug interactions or cellular redox conditions may also contribute to NAT activity. The recent findings reviewed here provide possible mechanisms by which these environmental determinants may affect NAT activity. Interestingly, these data could contribute to the development of selective NAT inhibitors for the treatment of cancer and microbial diseases.