Smallpox and monkeypox in non-human primates

In considering global eradication of smallpox the absence of an animal reservoir is important. Present knowledge of experimental infection of non-human primates with variola virus and of a related virus infection in monkeys, termed monkeypox, is examined.     

GnRH antagonists suppress prolactin release in non-human primates.

GnRH antagonists, such as Antide, are being evaluated for potential contraceptive applications. Although their contraceptive efficacy clearly results from their rapid inhibitory effects on gonadotropin release, there remains the possibility of other incidental effects. Under certain physiological conditions, the release of prolactin (Prl) appears to be temporally related to the secretion of luteinizing hormone (LH) and hence by inference to the secretion of GnRH. Here, we examined the effects of the GnRH antagonist Antide on the release of LH and Prl. Under agonadal conditions, a remarkable concordance was seen between LH and Prl pulses with up to 100% of pulses being coincident. Administration of Antide resulted in a rapid parallel decline in both LH and Prl with LH levels falling by 50% within 2 h and Prl levels falling by 30-40%. At this dose of Antide (1.0 mg/kg, sc), pulsatile release of LH and Prl continued albeit at a much reduced amplitude. The administration of a bolus of exogenous GnRH in the face of GnRHant-induced suppression resulted in prompt release of LH and Prl in all 3 monkeys. Since Antide inhibits the release of LH and Prl in a parallel fashion, and GnRH re-stimulates the release of both hormones in a parallel fashion, we conclude that the synchronous pulsatile release of LH and Prl observed in the agonadal monkey is due to a direct action of GnRH. What this action is for Prl release, and how it relates to the control of dopamine or other neuroendocrine mechanisms normally controlling the release of Prl remains unclear. It also remains to be seen whether this GnRH antagonist-induced suppression of Prl will have physiologic significance.     

Comparative feeding and nutrition in captive, non-human primates.

1. Food intake studies were carried out on three groups of captive primates (anthropoid apes (Pongidae), lemurs (Lemuridae) and marmosets (Callitrichidae). 2. Determination and analysis of the nutrient intakes were carried out by calculations based on food tables. The results from all groups were compared. 3. Marmosets were found to have higher intakes of energy and many other nutrients than the apes and lemurs. 4. The results suggest that there is a tendency towards over use of dietary supplements and foods of higher nutrient density for captive primates.     

Flow cytometric sorting of frozen-thawed spermatozoa in sheep and non-human primates

Research was conducted in sheep to determine an effective preparation method for high-purity sorting of frozen-thawed spermatozoa. The efficacy of sorting frozen-thawed spermatozoa was then investigated in several non-human primate species. An aliquot of each ejaculate (three rams, three ejaculates per ram) was processed as a fresh control (FRESH). Frozen spermatozoa were thawed and prepared for sorting by no further processing (FT-NEAT), washing (FT-WASH) or gradient centrifugation (FT-GRADIENT) and evaluated for motility at 1 h post-staining and motility and acrosomal status at 0 and 4 h post-sorting. Samples were analysed using a high-speed cell sorter. High levels of purity for X- and Y-enriched samples were achieved for all treatments (85-92%). The percentage of motile spermatozoa before sorting was lower (P < 0.05) for frozen-thawed samples (FT-NEAT: 32.7 +/- 2.5%; FT-WASH: 32.2 +/- 3.3%; FT-GRADIENT: 73.9 +/- 3.7%) compared with FRESH (83.3 +/- 1.2%). Post-sorting, the percentage of motile spermatozoa before and after incubation for FT-NEAT (60.0 +/- 5.1% and 27.2 +/- 6.1% for 0 and 4 h, respectively) was lower than that for FRESH (87.8 +/- 0.9% and 83.3 +/- 1.2% for 0 and 4 h, respectively; P < 0.05), FT-WASH (80.0 +/- 2.4% and 71.7 +/- 3.6% for 0 and 4 h, respectively; P < 0.05) and FT-GRADIENT (84.4 +/- 1.3% and 77.2 +/- 1.7% for 0 and 4 h, respectively; P < 0.05). Vanguard sperm migration distance through artificial cervical mucus was lower (P < 0.05) for FT-NEAT (17.7 +/- 1.7 mm) compared with FT-WASH (29.1 +/- 3.8 mm) and FT-GRADIENT (28.4 +/- 2.0 mm) and similar (P < 0.05) to FRESH (23.7 +/- 1.8 mm). Sample preparation using a modified wash method enabled high-purity sorting (range 86-97% purity) of frozen-thawed epididymal spermatozoa in the baboon (Papio hamadryas), common marmoset (Callithrix jacchus) and common chimpanzee (Pan troglodytes). For all non-human primate species, sorted spermatozoa were progressively motile (marmoset: 20.5 +/- 5.5%; baboon: 37.5 +/- 2.5%; chimpanzee: 73.0 +/- 2.0%), acrosome intact (marmoset: 68.5 +/- 7.5%; baboon: 89.5 +/- 1.5%; chimpanzee: 84.0 +/- 1.0%) and able to penetrate an artificial cervical mucus. In summary, high-purity sorting of frozen-thawed ram and non-human primate spermatozoa with recovery of progressively motile, acrosome-intact spermatozoa was possible after processing to remove cryodiluent.     

Environmental enrichment techniques in non-human primates. The case of Callitrichids

In this paper, we discuss issues concerning the welfare of non-human primates used in laboratory research from an eco-ethological standpoint and suggest means of improving welfare. Following a brief review of the use of non-human primates in European countries and of the legislation that governs this use, we illustrate how a thorough eco-ethological knowledge of the species being studied can play a vital role in improving both its conditions and the quality of the experimental protocols, arguing that the animal's quality of life is closely linked to the quality of data. As a model for describing environmental enrichment techniques, we have used the common marmoset (Callithrix jacchus).     

Experimental infection of non-human primates with a human rotavirus isolate

Several rotavirus candidate vaccines have been developed and are at various stages of evaluation. In order to assess the safety and efficacy of these candidate vaccines, an appropriate non-human primate model is desirable. In earlier studies, we reported the presence of naturally occurring anti-rotavirus antibodies in monkeys and demonstrated that parenteral vaccination of baboons led to production of specific rotavirus antibodies in their milk. In the present study, we assessed the possibility of developing the baboon and the vervet monkey as an animal model for rotavirus studies by inoculating them with a pathogenic human rotavirus isolate prepared from the fresh faeces obtained from a child suffering from rotavirus diarrhoea. Preliminary studies have showed excretion of rotavirus in the faeces of 5 of 5 vervets monkeys and 1 of 2 baboons, by antigen ELISA and SDS-PAGE. These results were confirmed by RT-PCR and electron microscopy. The animals also showed elevation of IgG and high titres of virus neutralising antibodies. These data indicate that baboon and vervet monkeys may be useful models for human rotavirus infection and for pre-clinical evaluation of rotavirus candidate vaccines.     

A microneedle patch containing measles vaccine is immunogenic in non-human primates

Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage.     

Energy expenditure in human pregnancy

Pregnancy and lactation are the most active anabolic phases of adult life and require marked changes in energy metabolism even in humans, in whom the energetic stress of reproduction is slight compared to most other species. Studies of the energetics of pregnancy started in the early 1900's when interest focused on the metabolism of the fetus in utero. More recently attention has turned to the implications of pregnancy for the mother herself. Data from the latest published studies now suggest that a physiological mechanism exists which can monitor a mother's energy stores and the adequacy of her diet during pregnancy, and can modify her metabolism accordingly. In particular, potent energy-sparing adaptations have been demonstrated in under-nourished mothers. Such adaptations would be anticipated to have important survival value when dietary intake is marginal. They have also been demonstrated to occur in some affluent women and therefore have implications when setting recommended dietary allowances for all women.     

Energy expenditure in HIV infection

Energy intake recommendations for adults should be based preferably on direct measurements of total daily energy expenditure (TDEE) in corresponding populations who are maintaining healthy body weight and satisfactory physical activity levels. During adolescence, pregnancy, and lactation, energy requirements should be based on TDEE plus the additional energy required to advance these physiologic states. With illness, energy expenditure and energy intake change, but nutritional intervention is not necessarily beneficial. This article reviews data on energy expenditure in HIV infection with a focus on adults, adolescents aged ≥14 y, and pregnant and lactating women. Resting energy expenditure (REE) in adults with untreated asymptomatic HIV is ~ 10% higher than in healthy control subjects. In asymptomatic adults receiving antiretroviral therapy, REE may be similarly increased. HIV wasting and secondary infections are also associated with increased REE. In contrast, TDEE is typically normal in asymptomatic HIV and decreased in HIV wasting and secondary infection. No direct measurements of REE or TDEE are available in adolescents or in pregnant or lactating women with HIV. On the basis of current data, energy intake may need to increase by ~ 10% in adults with asymptomatic HIV to maintain body weight. In adolescents and in pregnant and lactating women with asymptomatic HIV, energy requirements should approximate recommendations for their uninfected counterparts until further data are available. In the resource-rich world, the energy expenditure changes associated with HIV are unlikely to contribute to significant weight loss. More data are needed on energy expenditure in HIV-infected populations from developing nations, where concurrent malnutrition and coinfections are common.     

Energy expenditure in early infancy

The measurement of energy expenditure has wide applications in clinical and scientific studies. Ethical and practical problems, however, have limited the acquisition of information on total energy expenditure in infancy. The doubly-labelled-water technique, recently validated for use in infants, has now been used to measure, non-invasively, total energy expenditure in a cohort of forty-one normal, full-term infants at or close to 1.5, 3 and 6 months of age. Mean total energy expenditure was 270, 280 and 330 kJ/kg per d at these ages. Centiles for total energy expenditure in early infancy are presented; it is suggested such data are most appropriately expressed as kJ/square root (kg body-weight per d). These findings will be of importance in the re-evaluation of energy requirements in infancy and in the study of lesions in energy metabolism in disease states at this age.     

Energy expenditure in Alzheimer's disease

Alzheimer's disease type dementia is a growing health problem and is one of the leading causes of death among elderly people. Unexplained weight loss and cachexia is a frequent clinical finding in patients with Alzheimer's disease. It has been postulated that Alzheimer's disease may by characterized by dysfunction in body weight regulation. This brief review examines energy intake, energy expenditure and body composition in Alzheimer's disease. We consider whether inappropriately high levels of energy expenditure may contribute to unexplained weight loss and decline in nutritional status. Specifically, we will consider studies that have examined body composition, daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to problems of "wasting" has increased our knowledge regarding energy expenditure and physical activity levels in Alzheimer's patients. Although the number of studies are limited, results do not support the notion that a "hypermetabolic" state contributes to unexplained weight loss in Alzheimer's disease, even in cachectic patients. Clinical strategies aimed at developing feeding strategies to maintain adequate caloric intake and the restoration of energy balance should be a future area of investigation in Alzheimer's research.     

颅脑损伤病人静息能量消耗的观测

目的 研究不同颅脑损伤病人伤后静息能量的变化。方法 用开放式间接测热法测定40例不同程度颅脑损伤病人伤后前5天的氧耗量(VO2)、二氧化碳生成量(VCO2)、呼吸商(RQ)、静息能量消耗(REE)和24小时尿氮排出量。结果 有脑损伤组患者伤后氧耗量、静息能量消耗、24小时尿氮排出量比无脑损伤组明显增加，且与脑损伤程度成正比。结论 颅脑损伤患者脑组织和全身处于高能量代谢状态，对氧和能量的需求急剧增加，应根据损伤程度合理、适时地补充营养，以利康复。     

Energy expenditure of nonexercise activity

BACKGROUND: We found recently that changes in nonexercise activity thermogenesis (NEAT) mediate resistance to weight gain with overfeeding in sedentary adults. A potentially important, yet seldom investigated, component of NEAT is the energy expenditure of fidgeting-like activities. OBJECTIVE: Our goal was to measure changes in energy expenditure with fidgeting-like activities. DESIGN: Energy expenditure was measured in 24 subjects (17 women and 7 men x+/- SD body weight: 76 +/- 21 kg) while recumbent at rest, sitting motionless, standing motionless, partaking of self-selected fidgeting-like movements while seated and while standing, and walking on a treadmill at 1.6, 3.2, and 4.8 km/h (1, 2, and 3 mph). Measurements were performed by using a high-precision, indirect calorimeter connected to the subject via a transparent, lightweight facemask that enabled almost unrestricted movement. RESULTS: Compared with metabolic rate in the supine position (5.4 +/- 1.5 kJ/min), energy expenditure increased while sitting motionless by 4 +/- 6%, while fidgeting while seated by 54 +/- 29% (P: < 0.0001), while standing motionless by 13 +/- 8% (P: < 0.0001), while fidgeting while standing by 94 +/- 38% (P: < 0.0001), while walking at 1.6 km/h by 154 +/- 38% (P: < 0.0001), while walking at 3.2 km/h by 202 +/- 45% (P: < 0.0001), and while walking at 4.8 km/h by 292 +/- 81% (P: < 0.0001). There was a significant, positive correlation between changes in energy expenditure and body weight for fidgeting-like activities while standing (r = 0.43, P: = 0.02) but not while seated. CONCLUSIONS: There is marked variance between subjects in the energy expenditure associated with self-selected fidgeting-like activities. The thermogenic potential of fidgeting-like and low-grade activities is sufficiently great to substantively contribute to energy balance.