Observational study on the breeding performance of emus (Dromaius novaehollandiae) in Brazil / [Estudo observacional sobre o desempenho reprodutivo de emus (Dromaius novaehollandiae) no Brasil]

The objective of this study was to describe emus' breeding performance in Brazil at different ages, grouped in couples or colonies. The duration of the breeding season and the production of eggs per female housed were recorded, and the productivity and breeding variables were associated with the variation of the photoperiod. The total production of the flock was 180 eggs, and the breeding season lasted 167 days (April-September), a period with an average of 11 h and 11min of daylight. The breeding season lasted 113, 133 and 82 days, the numbers of eggs produced per female were 7.29, 25.67 and 17.3, and productivity values were 31.6, 38.6, and 45.4% in the groups of birds with ages of two, four and seven years, respectively. The breeding season in 2016 occurred between April and August in Brazil. Older birds tended to start breeding later. The production rate observations indicated that earlier peak production was associated with lower egg production potential. Finally, there was a tendency for better breeding performance of birds housed in couples than in groups with more birds.(AU)

O objetivo deste estudo foi descrever o desempenho reprodutivo de emus de diferentes idades, agrupados em casais ou em colônias, no Brasil. A duração da estação reprodutiva e a produção de ovos por fêmea alojada foram registradas, a produtividade e as variáveis reprodutivas foram associadas às variações no fotoperíodo. A produção total do lote de aves foi de 180 ovos, e a estação reprodutiva durou 167 dias (abril-setembro), período que apresentou fotoperíodo médio de 11 horas e 11 minutos. Nos grupos de aves de dois, quatro e sete anos de idade, a estação reprodutiva durou 113,, 133 e 82 dias, o número de ovos por fêmea foi de 7,29, 25,67 e 17,3 e a produtividade foi de 31,6, 38,6 e 45,4%, respectivamente. A estação reprodutiva em 2016 ocorreu entre abril e agosto no Brasil. Aves mais velhas tenderam a iniciar o período reprodutivo mais tarde. As observações na taxa de produção podem indicar que quanto mais precoce o pico produtivo, menor o potencial de produção de ovos em emus. Houve a tendência ao melhor desempenho reprodutivo das aves alojadas em casais em comparação com as alojadas em colônias.(AU)

Influência do sistema de criação em piso sobre cama e gaiola sobre as características ósseas e a qualidade físico-química e microbiológica de ovos de galinhas / Influence of the floor and cage creation system on the bony characteristics and the physical-chemical and microbiological quality of hen eggs

O experimento foi realizado no setor de avicultura/UFRRJ, utilizando 348 galinhas semipesadas (linhagem Dekalb Brown), com 52 semanas de idade, criadas sob dois sistemas de produção: cage-free e em gaiolas. Os dados obtidos pela análise físico-química e microbiológica dos ovos e a resistência óssea à quebra foram submetidos à análise de variância. No caso de ocorrerem efeitos dos diferentes sistemas de produção, foi aplicado o teste de Tukey a 5% de probabilidade para comparação das médias. A qualidade físico-química foi igualmente favorecida pelos dois sistemas de produção, indicando que as circunstâncias experimentais propiciaram condições adequadas para a formação de ovos de boa qualidade. O sistema de gaiola não desfavoreceu as características ósseas das galinhas, apontando que, em densidades adequadas, a gaiola pode não exercer um fator prejudicial para a qualidade óssea. O sistema de produção cage-free piorou a contaminação da casca, comprovando que ovos postos em ninhos são mais contaminados em comparação aos produzidos em gaiolas.(AU)

The experiment was carried out in the poultry sector / UFRRJ, using 348 semi-heavy hens (Dekalb Brown line), 52 weeks old, raised under two cage-free production systems and cages. The data obtained by the physical-chemical and microbiological analysis of the eggs and the bone resistance to the break were submitted to analysis of variance, in case of effects of the different production systems, the Tukey's test was applied at 5% of probability for comparison of the means. The physical-chemical quality was also favored by the two production systems, indicating that the experimental circumstances provided adequate conditions for the formation of good quality eggs. The cage system did not disfavor the bony characteristics of the hens, indicating that at suitable densities, the cage may not exert a detrimental factor to bone quality. The cage-free production system worsened shell contamination by proving that nesting eggs are more contaminated compared to those produced in cages.(AU)

Knowledge and practice of family planning and HIV-prevention behaviour among just delivered adolescents in Ecuador: the problem of adolescent pregnancies.

BACKGROUND: Adolescents constitute a high risk population for the spreading of sexually transmitted diseases, among them HIV/AIDS. Knowledge regarding reproductive issues among them is a key point in order to establish appropriate prevention programs. OBJECTIVE: Obtain information regarding the knowledge and practice related to family planning and HIV-prevention behaviour among adolescents of low income. METHODS: Adolescents aged 19 or less delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador were surveyed in the immediate postpartum period with a structured questionnaire designed for the purpose. RESULTS: During the study period, 357 pregnant adolescents were surveyed. Mean age was 17.2 +/- 1.4 years, 30.8% were aged 16 or less. Demographical and obstetrical history differences were found when comparing adolescents in relation to age and educational level. A high rate of mothers had unplanned pregnancies (63.3%) or did not know what family planning was (49.6%). Despite high knowledge of what a condom or an oral contraceptive was, few had used them in the past. The most frequently known family planning methods in this series, which was age dependent, were: oral contraceptives (90.2%), condoms (84.9%), parenteral (66.7%) and intrauterine devices (63.3%). The majority knew what HIV/AIDS infection was, the most important sources of knowledge being: television, high school source, and family or relatives. A high rate of adolescents had never had an HIV test performed in the past with one prior tested adolescent resulting in a positive result. There was a high rate of knowledge regarding the most frequent HIV transmission routes: sexual intercourse, contact with infected blood and vertical transmission. In this series, although condom use was the most known way for HIV protection, only 22.2% answered having intercourse protected with this method. CONCLUSION: In this adolescent series, older age was related to higher knowledge in family planning methods; in global despite finding a relatively high knowledge in family planning and HIV related issues, contraception use and HIV protection behaviour was low.

An anaerobic bioreactor allows the efficient degradation of HCH isomers in soil slurry.

The insecticide gamma-hexachlorocyclohexane (gamma-HCH or lindane), which has been extensively used for agricultural and medical purposes, presents high persistence and toxicity to the environment and low solubility. This study intends to assess the efficiency of an anaerobic reactor to degrade HCH isomers contained in soil slurry cultures. This study was developed in two phases: experiments in flasks to optimize the process parameters, and assessment of the slurry process in the anaerobic slurry reactor operated for an approximate period of a year. The influence of different environmental conditions was evaluated: the HCH concentration (25-100 mg HCH kg-1), the type of substrate (volatile fatty acids or starch), the sludge concentration (2-8 g VSS l-1) and the replacement of spiked soil to simulate a fed-batch operation (10-50%). The best results were obtained when the reactor was operated with a sludge concentration of 8 g VSS l-1, starch concentration of 2 g COD l-1 and soil replacements of 10-20%. Under these conditions, alpha- and gamma-HCH were completely degraded after 10d while nearly 90% beta- and delta-HCH were removed only after 50 d. According to the obtained results related to the total degradation of the HCH isomers and the degradation rates, especially high for alpha- and gamma-HCH, the anaerobic slurry reactor appears to be a good alternative for the degradation of the HCH isomers present in polluted soil.

Craniofacial imaging in orthodontics: historical perspective, current status, and future developments.

Rapid and substantial advances in imaging methods and technology have not always been expediently or adequately communicated to the practicing orthodontist. In this review we highlight contemporary imaging techniques and innovations in imaging that, in the future, are likely to greatly improve the depiction of craniofacial structures for use in diagnosis and treatment planning. In order to provide an appropriate background for this topic, we first discuss the evolution of craniofacial imaging in orthodontics and review the limitations of current methods, including the two-dimensional representation of three-dimensional anatomy, depiction as a patchwork of site-specific images, associated geometric errors, and images that have a limited point of view and are static in space and time. Three-dimensional computed tomography can be considered a partial solution to these limitations, but imaging costs, radiation exposure, and lack of soft tissue representation may make it unacceptable for routine orthodontics. A more complete solution might be achieved through digital processing of contemporary imaging technologies that would extend their capabilities, overcome many of their limitations, and result in an increase in the amount of relevant information obtained. Digital processes are currently being developed that create accurate multidimensional models that integrate form and function. These models will be interactive, linked to knowledge databases, and will provide the clinician with answers to pertinent questions. These advances in imaging are likely to enhance the accuracy and reliability of orthodontic diagnosis and treatment planning, and will be of importance in both clinical practice and research.

[Bourneville's tuberous sclerosis associated with double uterus and vagina (didelphic uterus)]. / Esclerosis tuberosa de Bourneville asociada a duplicidad uterovaginal (útero didelfo).

INTRODUCTION: We describe a case that fulfill the diagnostic criteria for the tuberous sclerosis (Bourneville disease), and presents a double uterus and double vagina (didelphic uterus). We have not found any reference ti this association in the literature (MEDLINE search from July 1986 to December 1996). CLINICAL CASE: A 38-year-old woman with mental retardation and seizures who has been with carbamazepine since age 14. In 1979 a double vagina was diagnosed and a resection of a vaginal thin wall was performed. Laparoscopy showed a double uterus and multiple granulations of mesothelial proliferation in the Douglas sac. She has a remarkable behavior disorder with conjugal and familiar problems as well as a chronic renal insufficiency. The examination show a patient with a mental retardation, cutaneous hypopigmentation, facial adenomas sebaceums of Pringle, and ataxia, the rest of exploration was normal. The cranial CT show multiples calcified subependymal nodules. An abdominopelvic CT revealed several lesions in the liver parenchymal, and the pancreas head, compatible with hamartomas or lipomas, big kidneys with bilateral cysts and angiomyolipomas, and didelphic uterus. The cytogenetic study showed a normal karyotype (46,XX) and the molecular cytogenetic study (Fluorescence in situ hybridization, FISH) of chromosomes 2, 3, 4, 9, 11, 12 and 16 showed no chromosomal reangement. CONCLUSIONS: Eventhough both Bourneville disease and didelphic uterus have individually been associated with chromosomal abnormalities, our cytogenetic studies show no chromosomal reangement or abnormality despite the coexistence of both disease in our patient. In the bibliographic search that we have performed we have not found any report of a case like the one we describe here.

Acetabular pneumatocyst containing air-fluid level.

The presence of intraosseous gas most commonly occurs in osteomyelitis, vacuum phenomenon, and postsurgery or posttraumatic states. Several cases of subchondral gas-filled lesions, called pneumatocysts, have also been described in the sacroiliac joint and clavicle, none of them with intralesional air-fluid level. These pneumatocysts are innocuous lesions of uncertain origin. We describe one case of acetabular pneumatocyst containing air-fluid level in a 62-year-old man with long-standing ankylosing spondylitis involving hip joint. To our knowledge, this is the first reported case of a pneumatocyst in an acetabular location containing air-fluid level.

[Cleidocranial dysostosis. Presentation of a case]. / Disostosis cleidocraneal. Presentación de un caso.

INTRODUCTION: Cleidocranial dysostosis is a syndrome defined by three characteristic findings: clavicular aplasia, retarded cranial ossification, and autosomic dominant hereditary transmission, with completed penetrance and full expression. However, the diagnosis cannot only be made based on those finding, because the polymorphism and extension of the lesions of this disease is important. Therefore, in this disease we can see upset in the second teething, short stature or dwarf, persistence of the biconvex appearance of vertebral body, bone hypoplastic iliac, retarded pubis branch ossification, wedge shape distal phalanges or with brachymesophalangia of the forefinger and fifth finger. CLINICAL CASE: We describe a 20 years old man, with cleidocranial dysostosis, without familiar antecedent (probable mutation), that come to our center for treatment of denture pathology with disabled eating, because anomalous distribution and eruption. He had clavicle agenesis, cranial ossification upset with wormian bones, vertebral bodies biconvex, superior maxillary hypoplastic, and dental packed in the superior maxillary and jawbone. CONCLUSIONS: Cleidocranial dysostosis is a hereditary disease, which can be of spontaneous apparition (mutation), has a grand polymorphism, affect the osseous development, predominate in the middle line membranous bone and is an entity of radiologic diagnosis.

Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor.

Indinavir (IDV) (also called CRIXIVAN, MK-639, or L-735,524) is a potent and selective inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease. During early clinical trials, in which patients initiated therapy with suboptimal dosages of IDV, we monitored the emergence of viral resistance to the inhibitor by genotypic and phenotypic characterization of primary HIV-1 isolates. Development of resistance coincided with variable patterns of multiple substitutions among at least 11 protease amino acid residues. No single substitution was present in all resistant isolates, indicating that resistance evolves through multiple genetic pathways. Despite this complexity, all of 29 resistant isolates tested exhibited alteration of residues M-46 (to I or L) and/or V-82 (to A, F, or T), suggesting that screening of these residues may be useful in predicting the emergence of resistance. We also extended our previous finding that IDV-resistant viral variants exhibit various patterns of cross-resistance to a diverse panel of HIV-1 protease inhibitors. Finally, we noted an association between the number of protease amino acid substitutions and the observed level of IDV resistance. No single substitution or pair of substitutions tested gave rise to measurable viral resistance to IDV. The evolution of this resistance was found to be cumulative, indicating the need for ongoing viral replication in this process. These observations strongly suggest that therapy should be initiated with the most efficacious regimen available, both to suppress viral spread and to inhibit the replication that is required for the evolution of resistance.

Synthesis of proinflammatory cytokines by human gingival fibroblasts in response to lipopolysaccharides and interleukin-1 beta.

We have examined the ability of gingival fibroblasts (GF) to participate in inflammatory response and function as accessory immune cells. The accessory immune function of GF cells was evaluated by their ability to elaborate proinflammatory cytokines following stimulation with lipopolysaccharides and interleukin-1 beta (IL-1 beta). Using three separate clonally derived and characterized human gingival fibroblast (GF) cell lines, we demonstrate that LPS from Actinobacillus actinomycetemcomitans (Aa) and Escherichia coli (Ec) induce mRNA and synthesis of proinflammatory cytokines, IL-1 beta, IL-6 and IL-8. IL-1 beta activation of GF cells showed that IL-1 beta non only induces the expression of IL-6, IL-8 and TNF-alpha, but also acts in an autocrine manner of GF cells and induces IL-1 beta expression. Furthermore, the continuous presence of IL-1 beta in GF cell cultures did not down regulate the response of GF cells to IL-1 beta. Pretreatment of GF cells with IL-1 beta resulted in the enhanced synthesis of TNF-alpha in response to additional IL-1 beta. These findings indicate that GF cells, in addition to providing structural support, may also function as accessory immune cells and play an important role in the initial inflammatory reaction as well as in the amplification of immune response.

LPS responsiveness in periodontal ligament cells is regulated by tumor necrosis factor-alpha.

Gingival fibroblasts function as accessory immune cells and are capable of synthesizing cytokines in response to lipopolysaccharides (LPS) from Gram-negative microbes. Recently, we have isolated, cloned, and characterized two cell lines which exhibit characteristics of periodontal ligament (PDL) cells. In this report, we demonstrate that PDL cells showing osteoblast-like phenotype are not LPS-responsive cells. However, treatment of PDL cells with tumor necrosis factor-alpha (TNF-alpha) inhibits the expression of their osteoblast-like characteristics. As a consequence of this TNF-alpha-induced phenotypic change, PDL cells become LPS-responsive, i.e., synthesize several pro-inflammatory cytokines in response to LPS. These phenotypic changes occur at concentrations of TNF-alpha that are frequently observed in tissue exudates during periodontal inflammation, suggesting a physiological significance for these in vitro observations. It is of interest that TNF-alpha-induced phenotypic changes in PDL cells are transient, since removal of rhTNF-alpha from the supernatants of PDL cell cultures results in re-acquisition of the osteoblast-like characteristics and lack of LPS responsiveness of PDL cells. These results suggest that TNF-alpha, by regulating the PDL cell functions, may allow these cells to participate in the disease process as accessory immune cells at the expense of their structural properties.

In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors.

Inhibitors of the human immunodeficiency virus type 1 (HIV-1) protease have entered clinical study as potential therapeutic agents for HIV-1 infection. The clinical efficacy of HIV-1 reverse transcriptase inhibitors has been limited by the emergence of resistant viral variants. Similarly, variants expressing resistance to protease inhibitors have been derived in cell culture. We now report the characterization of resistant variants isolated from patients undergoing therapy with the protease inhibitor MK-639 (formerly designated L-735,524). Five of these variants, isolated from four patients, exhibited cross-resistance to all members of a panel of six structurally diverse protease inhibitors. This suggests that combination therapy with multiple protease inhibitors may not prevent loss of antiviral activity resulting from resistance selection. In addition, previous therapy with one compound may abrogate the benefit of subsequent treatment with a second inhibitor.

L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor.

A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with Ki values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1IIIb-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.

L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.

To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily as a consequence of poor oral bioavailability in animal models. L-735,524 represents a class of human immunodeficiency virus type 1 protease inhibitors, termed hydroxyaminopentane amides, that incorporate a basic amine into the hydroxyethylene inhibitor backbone. L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles. The compound is effective against viruses resistant to reverse transcriptase inhibitors and is synergistically active when used in combination with reverse transcriptase inhibitors. Most importantly, L-735,524 exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals by using clinically acceptable formulations. Accordingly, the compound was selected for evaluation of safety and pharmacokinetic studies in humans.

HIV-1 protease inhibitors: synthesis and biological evaluation of glycopeptidemimetics.

A series of glycopeptidemimetics based on the hydroxyethylene Phe-Phe isostere have been synthesized and evaluated for their ability to inhibit the enzyme HIV-1 protease. Incorporation of carbohydrate moieties at the P'2-position and elimination of P'3 amino acid in our lead compound 1, provided inhibitors with only nanomolar potencies (400-800 nM). However, incorporation of a carbohydrate moiety at the P'3-position with branched chain amino acid at the P'2-position, resulted in inhibitors with subnanomolar potencies. Within this series, compound 21 was the most potent inhibitor (IC50 value 0.17 nM). This compound has also shown to block the spread of HIV-1 in T-lymphoid cells at an inhibitor concentration of 200 nM.

Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents: X-ray crystal structure assisted design.

By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.

L-696,229 specifically inhibits human immunodeficiency virus type 1 reverse transcriptase and possesses antiviral activity in vitro.

L-696,229 (3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-pyridin-2 (1H)-one) is a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity that possesses antiviral activity in cell culture (W.S. Saari, J.M. Hoffman, J.S. Wai, T.E. Fisher, C.S. Rooney, A.M. Smith, C.M. Thomas, M. E. Goldman, J. A. O'Brien, J. H. Nunberg, J. C. Quintero, W. A. Schleif, E. A. Emini, and P. S. Anderson, J. Med. Chem. 34:2922-2925, 1991). In the present study, the RT-inhibitory activity and antiviral properties were characterized in detail. The inhibition of RT activity was template-primer dependent with 50% inhibitory concentrations of 0.018 to 0.50 microM and was noncompetitive with respect to deoxynucleoside triphosphates. L-696,229 inhibited RT activity in a mutually exclusive manner with respect to either phosphonoformate or azidothymidine triphosphate and was a weak partial inhibitor of the RNase H activity associated with HIV-1 RT. The compound did not significantly inhibit other retroviral or cellular polymerases at 300 microM.L-696,229 inhibited the spread of HIV-1 infection in cell cultures with all cell types and viral isolates tested, including human peripheral blood mononuclear cells and a virus isolate resistant to azidothymidine.

Viral resistance to human immunodeficiency virus type 1-specific pyridinone reverse transcriptase inhibitors.

Human immunodeficiency virus type 1 (HIV-1)-specific pyridinone reverse transcriptase (RT) inhibitors prevent HIV-1 replication in cell culture (M. E. Goldman, J. H. Nunberg, J. A. O'Brien, J.C. Quintero, W. A. Schleif, K. F. Freund, S. L. Gaul, W. S. Saari, J. S. Wai, J. M. Hoffman, P. S. Anderson, D. J. Hupe, E. A. Emini, and A. M. Stern, Proc. Natl. Acad. Sci. USA 88:6863-6867, 1991). In contrast to nucleoside analog inhibitors, such as AZT, which need to be converted to triphosphates by host cells, these compounds act directly to inhibit RT via a mechanism which is noncompetitive with respect to deoxynucleoside triphosphates. As one approach to define the mechanism of action of pyridinone inhibitors, we isolated resistant mutants of HIV-1 in cell culture. Serial passage in the presence of inhibitor yielded virus which was 1,000-fold resistant to compounds of this class. Bacterially expressed RTs molecularly cloned from resistant viruses were also resistant. The resistant RT genes encoded two amino acid changes, K-103 to N and Y-181 to C, each of which contributed partial resistance. The mutation at amino acid 181 lies adjacent to the conserved YG/MDD motif found in most DNA and RNA polymerases. The mutation at amino acid 103 lies within a region of RT which may be involved in PPi binding. The resistant viruses, although sensitive to nucleoside analogs, were cross-resistant to the structurally unrelated RT inhibitors TIBO R82150 (R. Pauwels, K. Andries, J. Desmyter, D. Schols, M. J. Kukla, H. J. Breslin, A. Raeymaeckers, J. Van Gelder, R. Woestenborghs, J. Heykanti, K. Schellekens, M. A. C. Janssen, E. De Clercq, and P. A. J. Janssen, Nature [London] 343:470-474, 1990) and BI-RG-587 (V. J. Merluzzi, K. D. Hargrave, M. Labadia, K. Grozinger, M. Skoog, J. C. Wu, C.-K. Shih, K. Eckner, S. Hattox, J. Adams, A. S. Rosenthal, R. Faanes, R. J. Eckner, R. A. Koup, and J. L. Sullivan, Science 250:1411-1413, 1990). Thus, these nonnucleoside analog inhibitors may share a common binding site on RT and may all make up a single pharmacologic class of RT inhibitor. This observation may have important implications for the clinical development of these compounds.

Pyridinone derivatives: specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity.

Derivatives of pyridinones were found to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and prevent the spread of HIV-1 infection in cell culture without an appreciable effect on other retroviral or cellular polymerases. 3-[( (4,7-Dimethyl-1,3-benzoxazol-2-yl) methyl]amino ]-5-ethyl-6-methylpyridin-2(1H)-one (L-697,639) and 3-[[ (4,7-dichloro-1,3-benzoxazol-2-yl) methyl]amino]-5-ethyl-6-methylpyridin-2(1H)-one (L-697,661), two compounds within this series, had HIV-1 RT IC50 values in the range of 20-800 nM, depending upon the template-primer used. The most potent inhibition was obtained with rC.dG and dA.dT as template--primers. With rC.dG, reversible slow-binding non-competitive inhibition was observed. [3H]L-697,639 bound preferentially to enzyme-template-primer complexes. This binding was magnesium-dependent and saturable with a stoichiometry of 1 mol of [3H]L-697,639 per mol of RT heterodimer. Displacement of [3H]L-697,639 was seen with phosphonoformate. In human T-lymphoid-cell culture, L-697,639 and L-697,661 inhibited the spread of HIV-1 infection by at least 95% at concentrations of 12-200 nM. Synergism between 3'-azido-3'-deoxythymidine or dideoxyinosine and either of these compounds was also demonstrated in cell culture. Based upon their specificity for HIV-1 RT activity, template-primer dependence on potency and ability to displace [3H]L-697,639; a tetrahydroimidazo [4,5,1-jk] [1,4]-benzodiazepin-2(1H)-thione derivative R82150 and the dipyridodiazepinone BI-RG-587 appear to inhibit RT activity by the same mechanism as the pyridinones.

Yeast-expressed p55 precursor core protein of human immunodeficiency virus type 1 does not elicit protective immunity in chimpanzees.

Yeast-expressed p55 precursor core protein of human immunodeficiency virus type 1 (HIV-1) was used to immunize chimpanzees. The animals developed high titers of antibodies to p55 as well as to the p24 and p17 mature cleavage products of the core precursor. Virus-neutralizing antibodies were not elicited. The induced immune responses did not prevent establishment of HIV-1 infection following challenge of one immunized chimpanzee with live virus.