The use of non-human primates as animal models for the study of hepatitis viruses

Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus) can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus) is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

The role of nitric oxide in reproduction

Nitric oxide (NO) plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH). The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP). NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS) in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG).

Environmental color affects Nile tilapia reproduction

We investigated the effects of environmental color on the reproductive behavior of Nile tilapia, Oreochromis niloticus. Two environmental colors were tested by covering the aquarium (60 x 60 x 40 cm) with white (12 groups) or blue (13 groups) cellophane and observing reproductive behavior in groups of 2 males (10.27 ± 0.45 cm) and 3 females (10.78 ± 0.45 cm) each. After assignment to the respective environmental color (similar luminosity = 100 to 120 Lux), the animals were observed until reproduction (identified by eggs in the female's mouth) or up to 10 days after the first nest building. Photoperiod was from 6:00 h to 18:00 h every day. Food was offered in excess once a day and water quality was similar among aquaria. Daily observations were made at 8:00, 11:00, 14:00 and 17:00 h regarding: a) latency to the first nest, b) number of nests, c) gravel weight removed (the male excavates the nest in the bottom of the aquarium), d) nest area, and e) mouthbrooding incubation (indication of reproduction). The proportion of reproducing fish was significantly higher (6 of 13) in the group exposed to the blue color compared the group exposed to the white color (1 of 12; Goodman's test of proportions). Moreover, males under blue light removed significantly larger masses of gravel (blue = 310.70 ± 343.50 g > white = 130.38 ± 102.70 g; P = 0.01) and constructed wider nests (blue = 207.93 ± 207.80 cm² > white = 97.68 ± 70.64 cm²; P = 0.03) than the control (white). The other parameters did not differ significantly between light conditions. We concluded that reproduction in the presence of blue light was more frequent and intense than in the presence of white light.

Recombinant viruses as vaccines against viral diseases

Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appearance of dengue hemorrhagic fever. In order to study the evolutionary relationships and possible detection of the introduction of new dengue virus genotypes in Brazil in the last years, we analyzed partial nucleotide sequences of 52 Brazilian samples of both dengue type 1 and dengue type 2 isolated from 1988 to 2001 from highly endemic regions. A 240-nucleotide-long sequence from the envelope/nonstructural protein 1 gene junction was used for phylogenetic analysis. After comparing the nucleotide sequences originally obtained in this study to those previously studied by others, and analyzing the phylogenetic trees, we conclude that, after the initial introduction of the currently circulating dengue-1 and dengue-2 genotypes in Brazil, there has been no evidence of introduction of new genotypes since 1988. The increasing number of dengue hemorrhagic fever cases seen in Brazil in the last years is probably associated with secondary infections or with the introduction of new serotypes but not with the introduction of new genotypes.

Estrogens and male reproduction: a new concept

The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19) in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ß) in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.

Effect of obesity on rat reproduction and on the development of their adult offspring

The aim of the present study was to assess the reproductive parameters of obese Wistar rats and to determine the frequency of their obese adult offspring. Neonatal rats were divided into two groups: F1 generation, induced to obesity by monosodium glutamate (MSG; F1MSG, N = 30), and rats given saline (F1CON, N = 13). At 90 days of age all animals were mated, producing the F2 offspring (F2CON, N = 28; F2MSG, N = 15). Reproductive parameters (fertility, pregnancy, and delivery indexes) were evaluated in F1 rats. F2 newborns were weighed, and the obesity parameter for F1 and F2 generations was determined from months 5 to 7 of life. At month 7, periovarian fat was weighed and no differences were found. Mean newborn weight also did not differ. The F1 and F2MSG groups presented approximately 90% of obese rats since month 5 of life, whereas F1 and F2CON groups presented only 33%. There was no difference in periovarian weight among groups. Although obesity did not affect reproductive parameters, obese dams (F1MSG) were responsible for the appearance of obesity in the subsequent generation. Thus, obesity induced by neonatal MSG administration did not interfere with reproduction, but did provide a viable model for obesity in second-generation adult Wistar rats. This model might contribute to a better understanding of the pathophysiological mechanisms involved in transgenerational obesity.

Visual communication stimulates reproduction in Nile tilapia, Oreochromis niloticus (L.)

Reproductive fish behavior is affected by male-female interactions that stimulate physiological responses such as hormonal release and gonad development. During male-female interactions, visual and chemical communication can modulate fish reproduction. The aim of the present study was to test the effect of visual and chemical male-female interaction on the gonad development and reproductive behavior of the cichlid fish Nile tilapia, Oreochromis niloticus (L.). Fifty-six pairs were studied after being maintained for 5 days under one of the four conditions (N = 14 for each condition): 1) visual contact (V); 2) chemical contact (Ch); 3) chemical and visual contact (Ch+V); 4) no sensory contact (Iso) - males and females isolated. We compared the reproductive behavior (nesting, courtship and spawning) and gonadosomatic index (GSI) of pairs of fish under all four conditions. Visual communication enhanced the frequency of courtship in males (mean ± SEM; V: 24.79 ± 3.30, Ch+V: 20.74 ± 3.09, Ch: 0.1 ± 0.07, Iso: 4.68 ± 1.26 events/30 min; P < 0.05, two-way ANOVA with LSD post hoc test), induced spawning in females (3 spawning in V and also 3 in Ch+V condition), and increased GSI in males (mean ± SEM; V: 1.39 ± 0.08, Ch+V: 1.21 ± 0.08, Ch: 1.04 ± 0.07, Iso: 0.82 ± 0.07%; P < 0.05, two-way ANOVA with LSD post hoc test). Chemical communication did not affect the reproductive behavior of pairs nor did it enhance the effects of visual contact. Therefore, male-female visual communication is an effective cue, which stimulates reproduction among pairs of Nile tilapia.