A porcine model of acute, haematogenous, localized osteomyelitis due to Staphylococcus aureus: a pathomorphological study.

A porcine model of acute, haematogenous, localized osteomyelitis was established. Serial dilutions of Staphylococcus aureus [5-50-500-5000-50 000 CFU/kg body weight (BW) suspended in saline or saline alone] were inoculated into the right brachial artery of pigs (BW 15 kg) separated into six groups of two animals. During the infection, blood was collected for cultivation, and after the animals were killed from day 5 to 15, they were necropsied and tissues were sampled for histopathology. Animals receiving ≤500 CFU/kg BW were free of lesions. Pigs inoculated with 5000 and 50 000 CFU/kg BW only developed microabscesses in bones of the infected legs. In the centre of microabscesses, S. aureus was regularly demonstrated together with necrotic neutrophils. Often, bone lesions resulted in trabecular osteonecrosis. The present localized model of acute haematogenous osteomyelitis revealed a pattern of development and presence of lesions similar to the situation in children. Therefore, this model should be reliably applied in studies of this disease with respect to e.g. pathophysiology and pathomorphology. Moreover, because of the regional containment of the infection to a defined number of bones, the model should be applicable also for screening of new therapy strategies.

A non-traumatic Staphylococcus aureus osteomyelitis model in pigs.

BACKGROUND: The propensity for bacterial localization within bones of juvenile pigs is similar to the situation in humans, where haematogenously based osteomyelitis most commonly occurs in infants and children. In both pigs and humans, Staphylococcus aureus is a dominant cause of pyaemic lesions including osteomyelitis. The aim of the present study was to evaluate the pig as a model for the development of osteomyelitis following haematogenous spread of S. aureus. MATERIALS AND METHODS: Twelve animals were challenged intravenously once or twice with 1x10(8) bacteria/kg body weight and euthanased consecutively from 6 h to 48 h after challenge. Following euthanasia, tissues were sampled from the lungs and bones for histology and immunohistochemical staining of vessels, different inflammatiory cells, apoptosis cells, and S. aureus. RESULTS: Disseminated microabscesses developed within the lungs by 6 h but had disappeared at 48 h. Within the metaphyseal area of bones, microabscesses developed after 12 h and progressed until 48 h after challenge. Within bones, lesions were localized in separate foci from where the infection progressed towards the growth plate, which was in some cases bypassed due to bacterial spread through transphyseal vascular channels. Often, bone lesions resulted in trabecular osteosis, in which apoptotic cells were sometimes present. CONCLUSION: The model revealed a pattern of development and presence of lesions similar to the frequently occurring osteomyelitic lesions, especially in pre-pubertal children following haematogenous spread of S. aureus. Therefore, this model can be reliably applied in studies of this disease with respect to pathophysiology, pathomorphology, impact of strain virulence, and therapy.

Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs.

BACKGROUND: The neonatal brain is particularly vulnerable to imbalances in redox homeostasis because of rapid growth and immature antioxidant systems. Vitamin C has been shown to have a key function in the brain, and during states of deficiency it is able to retain higher concentrations of vitamin C than other organs. However, because neurons maintain one of the highest intracellular concentrations of vitamin C in the organism, the brain may still be more sensitive to deficiency despite these preventive measures. OBJECTIVE: The objective was to study the potential link between chronic vitamin C deficiency and neuronal damage in newborn guinea pigs. DESIGN: Thirty 6- to 7-d-old guinea pigs were randomly assigned to 2 groups to receive either a vitamin C-sufficient diet or the same diet containing a low concentration of vitamin C (but adequate to prevent scurvy) for 2 mo. Spatial memory was assessed by the Morris Water Maze, and hippocampal neuron numbers were quantified by stereologic techniques. RESULTS: The results showed a reduction in spatial memory (P < 0.05) and an increased time to first platform hit (P < 0.05) in deficient animals compared with controls. The deficient animals had a lower total number of neurons in hippocampal subdivisions (dentate gyrus, cornu ammonis 1, and cornu ammonis 2-3) than did the normal controls (P < 0.05). CONCLUSIONS: Our data show that vitamin C deficiency in early postnatal life results in impaired neuronal development and a functional decrease in spatial memory in guinea pigs. We speculate that this unrecognized effect of vitamin C deficiency may have clinical implications for high-risk individuals, such as in children born from vitamin C-deficient mothers.