Neonatal lipopolysaccharide exposure does not diminish the innate immune response to a subsequent lipopolysaccharide challenge in Holstein bull calves.

The innate immune response following experimental mastitis is quite variable between individual dairy cattle. An inflammatory response that minimizes collateral damage to the mammary gland while still effectively resolving the infection following pathogen exposure is beneficial to dairy producers. The ability of a lipopolysaccharide (LPS) exposure in early life to generate a low-responding phenotype and thus reduce the inflammatory response to a later-life LPS challenge was investigated in neonatal bull calves. Ten Holstein bull calves were randomly assigned to either an early life LPS (ELL) group (n=5) or an early life saline (ELS) group (n=5). At 7d of age, calves received either LPS or saline, and at 32d of age, all calves were challenged with an intravenous dose of LPS to determine the effect of the early life treatment (LPS or saline) on the immune response generated toward a subsequent LPS challenge. Dermal fibroblast and monocyte-derived macrophage cultures from each calf were established at age 20 and 27d, respectively, to model sustained effects from the early life LPS exposure on gene expression and protein production of components within the LPS response pathway. The ELL calves had greater levels of plasma IL-6 and tumor necrosis factor-α than the ELS calves following the early life LPS or saline treatments. However, levels of these 2 immune markers were similar between ELL and ELS calves when both groups were subsequently challenged with LPS. A comparison of the in vitro LPS responses of the ELL and ELS calves revealed similar patterns of protein production and gene expression following an LPS challenge of both dermal fibroblast and monocyte-derived macrophage cultures established from the treatment groups. Whereas an early life exposure to LPS did not result in a dampened inflammatory response toward a later LPS challenge in these neonatal bull calves, the potential that exposure to inflammation or stress in early life or in utero can create an offspring with a low-responding phenotype as an adult is intriguing and has been documented in rodents. Further work is needed to determine if an inflammatory exposure in utero in a dairy animal would result in a low-responding innate immune phenotype.

Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist and its relation to mastitis caused by intramammary challenge with Staphylococcus aureus.

Staphylococcus aureus is a common cause of chronic mammary gland infections in dairy cattle. However, the inflammatory response and duration of infection following pathogen exposure is variable between individual animals. To investigate interanimal differences in immune response, dermal fibroblast cultures were established from skin biopsies collected from 50 early lactation Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to assign a response phenotype to the animals. Five high-responding and 5 low-responding animals were then selected for an intramammary challenge with S. aureus to evaluate differences in the inflammatory response, chronicity of infection, and development of antibodies to the pathogen. All animals exhibited clinical symptoms of mastitis at 24h postchallenge. Animals previously classified as high responders experienced a greater inflammatory response characterized by elevated levels of milk somatic cell count, IL-8, and BSA following the challenge compared with low responders. In addition, antibodies toward the challenge strain of S. aureus reached higher levels in whey from the challenged gland of high responders compared with low responders. Despite the antibody response, all 5 high responders were chronically infected for the 6-wk duration of the study, whereas 2 of the low responders cleared the infection, although 1 of these did become reinfected. The observed differences between animals classified as low and high responders based on their fibroblast responsiveness suggests that this cell type can be used to further examine the causes of interanimal variation in response to mammary infection.

Between-cow variation in dermal fibroblast response to lipopolysaccharide reflected in resolution of inflammation during Escherichia coli mastitis.

Effective response to mammary gland infection depends on efficient early innate immune response. The desired response would be one that is sufficient to clear the infection with a rapid return to the production of high-quality milk and limited tissue damage. In this study, 43 early lactation cows were ranked based on the ability of their fibroblasts to produce IL-8 in response to Escherichia coli lipopolysaccharide. Subsequently, the effect of a low or high response phenotype on the response to E. coli mastitis was determined. Untreated fibroblasts produced no detectable IL-8, whereas the range of IL-8 production in response to LPS (100 ng/mL) was approximately 7-fold between the lowest and highest responding cultures. Similar patterns of between-cow variation were observed in fibroblast production of IL-8 and IL-6 in response to IL-1ß and Pam2CSK4 (a synthetic diacylated lipopeptide ligand). Four low and 4 high responder cows were challenged in late lactation with intramammary infusion of E. coli. All cows developed clinical mastitis in the challenged quarters and all cows cleared the infection within 8 d. However, somatic cell count began to decline earlier in the low responder group, and milk BSA concentration (an indicator of tissue damage) was also lower in low responders compared with high responders. Milk production from the challenged quarter was markedly depressed in both groups, but returned toward prechallenge values earlier in low responder cows. Dermal fibroblast cells appear predictive of a cow's response to mastitis. In this study, the low responder phenotype was sufficient to contain an E. coli infection with a more rapid return to the production of high quality milk.

Scrub typhus (Orientia tsutsugamushi), spotted fever (Rickettsia australis) and dengue fever as possible causes of mysterious deaths in the Strickland Gorge area of Southern Highlands and West Sepik Provinces of Papua New Guinea.

A medical investigation was carried out in April 2001 into an outbreak of a mysterious haemorrhagic disease and deaths in the remote picturesque Strickland River area of Papua New Guinea (PNG). The area is in part of the Southern Highlands and West Sepik Provinces and situated downstream from the Porgera Joint Venture gold mine. 9 villages were visited and 140 persons, consisting of immediate blood relatives of the deceased (cases) and others in the village picked at random (controls), were physically examined. Specimens of blood, urine and faeces were collected from each person for laboratory tests in PNG and Australia. Positive sera for dengue (15%) and Japanese encephalitis (JE) (6%) were identified. Surprisingly, a number of the sera were positive for scrub typhus (Orientia tsutsugamushi) (28%) and spotted fever (Rickettsia australis) (11%). The last reported cases of scrub typhus in PNG were during World War Two among the allied troops. This is the first time spotted fever (R. australis) has been reported in PNG. These conditions may have been the cause of the deaths described by the villagers. However, there were significantly more dengue-positive results among relatives of the deceased than non-relatives though no such difference was found with rickettsial infections: haemorrhagic dengue fever is thus the most likely cause of this recurring outbreak. Mining did not appear to be a direct causal factor for the deaths in the area.

Temporal lobe lesion-induced obesity in rats: an anatomical investigation of the posterior amygdala and hippocampal formation.

Bilateral lesions centered in the posterodorsal amygdala of female rats resulted in hyperphagia and excessive weight gain (mean = 65.3 g in 20 days compared to 6.8 g for control animals). The brain damage always extended posteriorly into the ventral hippocampal formation. However, lesions that were confined to the ventral hippocampus or amygdalohippocampal area had no effect on daily food intake or body weight, nor did lesions at any other hippocampal site. In a previous study, lesions of the basolateral, corticomedial, and anterior groups of amygdaloid nuclei failed to affect food intake or body weight. It is concluded that the posterodorsal aspect of the amygdala is the critical site for this experimentally induced obesity syndrome. New coordinates for the effective site are presented.

Community screening for diabetes in the National Capital District, Papua New Guinea: is betelnut chewing a risk factor for diabetes?

This cross-sectional study was conducted intermittently in the National Capital District of Papua New Guinea from 1995 to 1999. Fasting capillary blood glucose (FCBG) was used as the screening test for diabetes. Blood glucose level was measured using the standard pocket-size reflectometer. A total of 769 individuals were screened. There were 385 males and 384 females ranging in age from 12 to 76 years. High FCBG (hFCBG) (> or = 7.0 mmol/l) was found in 13% of those examined and was associated with older age (p = 0.001), high body mass index (p = 0.027), coastal region of origin (p = 0.012) and betelnut chewing (p < 0.001). The prevalence of hFCBG in those of highland origin was 9% compared to 16% among the coastal people. Among the Seventh Day Adventists, the prevalence of hFCBG was 10%. The overall prevalence of hFCBG was the same in males and females but in those aged 35 years or more the prevalence was higher in females. Multivariate analysis (logistic regression) showed that hFCBG was significantly associated with betelnut chewing (p = 0.005) and age (p = 0.028); the body mass index (p = 0.061) and region of origin (p = 0.056) associations approached statistical significance. Sex and smoking were not statistically significant factors. In conclusion, diabetes is common in the 'healthy' population of Port Moresby and rates in highlanders living there were surprisingly high. In this study, betelnut chewing was independently associated with diabetes, and may therefore be a risk factor for diabetes mellitus.

Diabetes: the by-product of westernization in Papua New Guinea.

Before the 1960s diabetes was rare in Papua New Guinea. But by late 1970s there was evidence that diabetes type 2 was increasing among some urban dwellers. The problem is getting worse and in some urban communities the prevalence of diabetes has doubled within 14 years. Unfortunately no one knows the exact magnitude of the problem. Secondly there are simply not enough resources to handle the current known cases. This is compounded by the fact that many Papua New Guineans welcome western lifestyle with open arms. A change of eating habits and lifestyle is vital if any change is to be made to this by-product of westernization.

User charges and utilisation of obstetric services in the National Capital District, Papua New Guinea.

This cross-sectional study examined user charges on the utilization of obstetric services in the 4 urban clinics and antenatal and postnatal wards of the Port Moresby General Hospital (PMGH) in the National Capital District, Papua New Guinea. Analysis of previous records showed attendance to antenatal clinics on first visits declined by 30% soon after the introduction of use charges. However, the frequency of attendances increased and stabilized 12 months after the introduction of the user fees. The mean age for the 482 mothers interviewed was 25 years (range = 15-46 years, SD = 5.3). Over 50% of mothers were between 15-24 years of age and 47% over 24 years. 98.6% were married and a small proportion were single and divorcees (1.4%). Over 85% of mothers had some formal education while 15% without. The frequency of hospital deliveries did not change despite increased in user charges in the PMGH delivery and postnatal care services. Twenty four percent of mothers interviewed indicated they were unable to pay user fees. Mothers unable to pay the user charges were those without income or whose spouses were without regular income. In 23.2% of mothers with some income, majority indicated ability to pay the user fees. There was a minority group of mothers without income but relied heavily on their spouses income to meet the user fees. Mothers living in households with some income were twice more likely (OR = 2.18, 95% CI 1.24-3.83, p = 0.002) to have the ability to pay user fees than those without. Two other significant indicators associated with mother's ability to pay user fees were employment and knowledge of existence of the user charges. Over 79% of mothers indicated willingness to pay user charge fees. Mothers with income were nearly three times more likely (OR = 2.77, 95% CI 1.36-5.78, p = 0.002) willing to pay user charge fees than those without income. Other indicators that showed significant association with willingness to pay user charge fees were employment, income and knowledge of user charges. Although small proportion of mothers were unable to meet the user charges, results in this study showed majority of mothers were able and willing to pay user charges if they had prior information to the charges and supported by some form of income. The results of the study suggests the typical support practised by the society where the spouse and relatives assist with health care especially with maternal health is encouraging. However, the scope of this study cannot be used to generalise the trend in PNG because the scenerio in the rural areas will vary from urban.