Emerging clinical experience with vaccines against group B meningococcal disease.

The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus (MenB). Both of these vaccines are based on sub-capsular proteins of the meningococcus, an approach that overcomes the challenges set by the poorly immunogenic MenB polysaccharide capsule but adds complexity to predicting and measuring the impact of their use. This review describes the development and use of MenB vaccines to date, from the use of outer membrane vesicle (OMV) vaccines in MenB outbreaks around the world, to emerging evidence on the effectiveness of the newly available vaccines. While recent data from the United Kingdom supports the potential for protein-based vaccines to provide direct protection against MenB disease in immunised children, further research is required to understand the breadth and duration of this protection. A more detailed understanding of the impact of immunisation with these vaccines on nasopharyngeal carriage of the meningococcus is also required, to inform both their potential to induce herd immunity and to preferentially select for carriage of strains not susceptible to vaccine-induced antibodies. Although a full understanding of the potential impact of these vaccines will only be possible with this additional information, the availability of new tools to prevent the devastating effect of invasive MenB disease is a significant breakthrough in the fight against childhood sepsis and meningitis.

Uptake of SigmaDDT, arsenic, cadmium, copper, and lead by lettuce and radish grown in contaminated horticultural soils.

Horticultural soils can contain elevated concentrations of selected trace elements and organochlorine pesticides as a result of long-term use of agrichemicals and soil amendments. A glasshouse study was undertaken to assess the uptake of weathered SigmaDDT {sum of the p, p'- and o, p-isomers of DDT [1,1,1-trichloro-2,2- bis( p-chlorophenyl)ethane], DDE [1,1-dichloro-2,2- bis( p-chlorophenyl)ethylene] and DDD[1,1-dichloro-2,2- bis( p-chlorophenyl)ethane]}, arsenic (As), cadmium (Cd), copper (Cu), and lead (Pb) residues by lettuce ( Lactuca sativa) and radish ( Raphanus sativus) from field-aged New Zealand horticultural soils. Concentrations of SigmaDDT, DDT, DDE, Cd, Cu, and Pb in lettuce increased with increasing soil concentrations. In radish, similar relationships were observed for SigmaDDT, DDE, and Cu. The bioaccumulation factors were less than 1 with the exception of Cd and decreased with increasing soil concentrations. Lettuce Cd concentrations for plants grown on four out of 10 assayed soils were equivalent to or exceeded the New Zealand food standard for leafy vegetables of 0.1 mg kg (-1) fresh weight. Concentrations of As, Pb, and SigmaDDT did not exceed available food standards. Overall, these results demonstrate that aged residues of SigmaDDT, As, Cd, Cu, and Pb in horticultural soils have remained phytoavailable. To be protective of human health, site-specific risk assessments and soil guideline derivations for residential settings with vegetable gardens need to consider the produce consumption pathway.

Presumptive tremorgenic mycotoxicosis in a dog in New Zealand, after eating mouldy walnuts.

CASE HISTORY: A 1-year-old, intact male Labrador-cross dog vomited after eating walnuts that had been on the ground for 5 months. The dog then developed tremors, ataxia, increased salivation, and hyperaesthesia. CLINICAL FINDINGS: The dog had marked generalised tremors, ataxia and a temperature of 39.9 degrees C. Both pupils were of normal size and normally responsive to light. Vomiting was induced, and walnut shell was visible in the vomitus. DIAGNOSIS: Due to the sudden onset of tremors, lack of exposure to other convulsive toxins, and the evidence of ingestion of walnuts, the provisional diagnosis was tremorgenic mycotoxicosis. The dog was treated symptomatically, and made a full recovery over 18 hours. Tremorgenic mycotoxins were detected within walnuts collected from the dog's environment. CLINICAL RELEVANCE: Fungi that produce tremorgenic mycotoxins are present in New Zealand. Intoxication should be suspected in dogs that suddenly develop muscle tremors, especially if there is a history of ingestion of mouldy food 2-3 hours prior to the development of tremors.

Studies of transformation and particle-binding of resin acids during oxidative treatment of effluent from two New Zealand pulp mills.

Reactor studies of aerobic degradation of effluent from the first and last ponds of the treatment system of two New Zealand pulp and paper mills indicated that filterable BOD(5), resin acids and transformed resin acids, free and bound, degraded at similar rates. During oxidative treatment the resin acids of untreated effluent became increasingly bound to particulate material and a sediment high in abiet-13-enoic acid was formed.

Sapogenin levels in Narthecium ossifragum plants and Ovis aries lamb faeces during two alveld outbreaks in Møre og Romsdal, Norway, 2001.

The proposal that saponins produced by the lily bog asphodel (Narthecium ossifragum) may be the direct cause of the hepatogenous photosensitization disease alveld seen in Norwegian lambs was investigated by comparing sapogenin levels in two control and two toxic pastures, and in faeces from lambs grazing the four pastures in the Halsa and Surnadal municipalities, Møre og Romsdal county, Norway. Generally similar levels of sapogenins, determined after hydrolysis of parent plant saponins, were found in Narthecium leaves collected in June/July 2001 from the two alveld outbreak areas and two nearby control areas. Differences in the median sapogenin levels determined for leaf samples in outbreak and control areas were not statistically significant. The total level of free and conjugated sapogenins in faeces recovered from the rectums of lambs grazing the outbreak and control pastures areas varied greatly. The results obtained do not support the hypothesis that a dose-response relationship exists between Narthecium saponin levels and the occurrence of alveld outbreaks.

Trace element and Sigma DDT concentrations in horticultural soils from the Tasman, Waikato and Auckland regions of New Zealand.

The long-term routine use of agrichemicals can result in elevated levels of trace elements and persistent organic pollutants in soils. Trace element concentrations and SigmaDDT levels were measured in soil (0-7.5 cm) samples collected from horticultural and grazing properties in 3 regions of New Zealand (Auckland, Tasman and Waikato). Elevated levels of arsenic (<2 to 58 mg kg(-1)), cadmium (<0.1 to 1.5 mg kg(-1)), copper (5 to 523 mg kg(-1)), lead (5 to 243 mg kg(-1)) and SigmaDDT (<0.03 to 34.5 mg kg(-1)) were detected in soils from all 3 regions. With the exception of cadmium and zinc, significantly higher levels of contaminants were generally detected in horticultural soils than in grazing soils. Our results have implications for the on-going use of agrichemicals as concentrations of cadmium, copper, tin and zinc in some samples exceeded ecotoxicity based soil criteria. The p,p'-DDE:DDT ratios indicate that the degradation of DDT in NZ horticultural soils may be inhibited by the co-contamination with trace elements.

Summer variation in the concentration of steroidal sapogenins in and the degree of fungal infection on Narthecium ossifragum plants from Møre og Romsdal County, Norway.

Thirty-nine leaf samples of Narthecium ossifragum collected from eight sites in Møre og Romsdal County, Norway, during June-September 1997 and 41 leaf samples collected at five sites in the same county during June-August 1998 were analysed for the concentrations of steroidal sapogenins using GC-MS. The 1998 samples were also examined for fungal elements (conidia and hyphae) after incubation in a moist chamber for 10-14 days. The highest 1997 and 1998 leaf sapogenin concentrations (4881 and 7115 mg/kg dry matter, respectively) were 13-14 times greater than the lowest sapogenin concentrations found (344 and 531 mg/kg dry matter, respectively). The results did not reveal systematic differences in sapogenin concentrations between the two seasons, or between samples harvested early or late in the same seasons, or between sapogenin concentrations in plants harvested at different sites. Cladosporium magnusianum was the predominant fungus found in the samples. The degree of fungal infection on the samples was in generally low, but the number of C. magnusianum colonies in the moist chamber preparations and fungal elements (conidia and hyphae) in leaf washings and on leaves tended to increase with time. Factor analysis and multiple regression analysis performed on the chemical and fungal results suggest that sporulation may have occurred in the fungi in response to increase in sapogenin concentrations.

Structural biology of the cell adhesion protein CD2: from molecular recognition to protein folding and design.

CD2 (cluster of differentiation 2) is a cell adhesion molecule expressed on T cells and is recognized as a target for CD48 (rats) and CD58 (humans). Tremendous progress has been achieved in understanding the function of CD2, the mechanism of molecular recognition and protein folding, thus, leading towards the use of this protein as a scaffold for protein design. CD2 has been shown to set quantitative thresholds in T cell activation both in vivo and in vitro. Further, intracellular CD2 signaling pathways and networks are being discovered by the identification of several cytosolic tail binding proteins. In addition, a new method for directly measuring heterophilic adhesion has been developed. The functional "hot spot" for the adhesion surface of CD2 and CD58 has been dissected. Detailed NMR studies reveal that rat CD2 weakly self-associates to form a homodimeric structure in solution. Dynamic interaction of CD2 with the GYF and SH3 domains has been investigated. CD2 has been shown to form fibrils in the presence of 2,2,2-trifluoroethanol (TFE) and at low pH. Furthermore, kinetic studies have been completed to monitor the effect of surface hydrophobic residues and intramolecular bridges on the folding pathways of CD2. Our lab has de novo designed single calcium-binding sites into domain 1 of rat CD2 (CD2-D1) with strong metal selectivity. In addition, the EF-hand motifs have been grafted into CD2 to understand the site-specific calcium-binding affinity of calmodulin and calcium-dependent cell adhesion.

Preliminary evidence that copper inhibits the degradation of DDT to DDE in pip and stonefruit orchard soils in the Auckland region, New Zealand.

Orchards (n=13) were sampled as part of a larger survey investigating agrichemical residues (pesticides and trace elements) in cropping soils in the Auckland region, New Zealand. SigmaDDT concentrations in orchard soils ranged from <0.03 to 24.41 mg kg(-1). DDT (o,p'- and p,p'-) comprised at least 40% of the SigmaDDT residues in 67% of orchards in which DDT residues were detected. There was a highly significant negative correlation (-0.924, P<0.001) between copper concentration (21-490 mg kg-1) and the ratio of DDE:DDT (0.4-5.2) in pip and stonefruit orchard soils. In further investigations involving five pip and stone fruit orchard sites and one grazing paddock it was found that soil respiration and the ratio of soil microbial carbon to soil carbon (%Cmic/Org-C) in orchard soils decreased with increasing copper concentration. These findings are consistent with the conclusion that elevated soil copper concentrations in pip and stone fruit orchard soils in the Auckland region may have reduced the ability of the indigenous soil microbial community to degrade DDT to DDE

Accumulation of sapogenin conjugates and histological changes in the liver and kidneys of lambs suffering from alveld, a hepatogenous photosensitization disease of sheep grazing Narthecium ossifragum.

Sixteen lambs exhibiting hepatogenous photosensitization (alveld) after grazing pasture containing Narthecium ossifragum and seven nonphotosensitized lambs grazing the same pastures were studied. All the alveld-affected lambs revealed liver damage dominated by single cell necrosis, portal fibroplasia and bile duct proliferation. Crystalloid clefts were demonstrated in the bile ducts of two and in the hepatocytes and Kupffer cells of nine photosensitized lambs. Plasma bilirubin concentration was severely increased in ten of the cases of alveld whereas the activity of aspartate aminotransferase was moderately to severely increased in seven cases. The activity of glutamate dehydrogenase was moderately elevated in one of the photosensitized lambs. The main histopathological findings in the kidneys from the alveld-affected lambs were dilated tubules, often with eosinophilic material in the tubular lumina. Regenerative changes were seen in a large proportion of the renal sections. Elevated plasma concentrations of urea and creatinine, and the renal histopathological changes, suggested that the photosensitized lambs had been through a phase of renal injury. Analysis of the free and conjugated sapogenin content in liver tissue and bile was performed by gas chromatography-mass spectrometry. There were significantly higher concentrations of conjugated episapogenins in both the liver and bile in the alveld-affected lambs than in the nonphotosensitized lambs.

Ruminal metabolism in sheep of saponins from Yucca schidigera.

Fifty-five mg per kg live weight of crystallized Yucca schidigera saponins, corresponding to 26 mg/kg live weight of sapogenins, was given daily intraruminally to two lambs for 11 consecutive days. Neither of the lambs showed any sign of toxicity throughout the experimental period. One lamb was killed 5 h after the last dose and GC-MS analysis of the free and conjugated sapogenin content samples of liver, and of the contents of the rumen, omasum, abomasum, duodenum, jejunum, ileum, colon and rectum, of faecal samples collected before dosing started, and of parts of the administered Yucca saponin were performed. The Yucca material contained mainly sarsasapogenin and smilagenin saponins. Ingested saponins were quickly hydrolysed in the rumen to free sapogenins and, in part, epimerized at C-3 to afford episapogenins. The absorption of free sapogenins appeared to occur in the jejunum. The metabolism of Yucca saponins was identical to that of Narthecium ossifragum saponins, and it is suggested that Yucca saponins could replace N. ossifragum saponins for toxicity studies on the latter plant.

Seasonal variation in cotyledoside concentration of Tylecodon wallichii (Harv.) Tölken subsp. wallichii sampled in a krimpsiekte-prevalent region.

Krimpsiekte, an economically important neuromuscular affliction of small stock, follows upon ingestion of certain members of the Crassulaceae (plakkies) containing cumulative neurotoxic bufadienolides. Tylecodon wallichii (Harv.) Tölken subsp. wallichii is probably the most important species of the group of plants causing krimpsiekte. The growing tip of the stem and various other plant parts of T. wallichii, when available, were collected monthly. The seasonal variation in cotyledoside content of the plant was measured. Cotyledoside concentration was determined by high performance liquid chromatographic-electrospray mass spectrometry analysis (HPLC-ESMS). The cotyledoside concentration in the plant stems fluctuated substantially during the year, but tended to be higher in the cold winter months and increased again in the spring and early summer. Elevated plant stem concentrations corresponded with natural field outbreaks of krimpsiekte, which usually occur during the winter to early summer. The highest cotyledoside concentrations were detected in the flowering stalk. Cotyledoside was not the only component of this type in the plant, as mass spectrometry revealed the presence of other, possibly related, compounds.

C-27 and C-3 glucosylation of diosgenin by cell suspension cultures of Costus speciosus.

3-O-[beta-D-glucopyranosyl-(1"--> 2')-beta-D-glucopyranosyl], 27-O-beta-D-glucopyranosyl-(25R)-spirost-5-ene-3beta,27-diol was isolated from cell suspension cultures of Costus speciosus, following incubation with diosgenin, and its structure was elucidated using a combination of one- and two-dimensional 1H and 13C NMR spectral data, and positive and negative ion ESMS spectral data.

Aerobic exercise interventions for people with HIV/AIDS.

BACKGROUND: The profile of HIV infection is constantly changing. Although once viewed as an illness progressing to death, HIV infection now presents as a chronic infection characterized by unpredictable cycles of wellness and illness. Thus, the needs of this population have increasingly included management of impairments, disabilities and handicaps. Exercise is a key management strategy employed by rehabilitation professionals to address these issues. Exercise has been shown to improve strength, cardiovascular function, and psychological status in seronegative populations (see Eds., Bouchard, C., Shephard, R.J., & Stephens, T. (1993). Physical Activity, Fitness, and Health. Champaign, IL: Human Kinetics Publishers.) But what are the effects of exercise for people living with HIV infection? If the risks and benefits of exercise for people living with HIV infection are better understood, appropriate exercise prescription may be practiced by health care providers. Improved exercise prescription may enhance the effectiveness of HIV management, thus improving overall outcomes for people living with HIV infection. OBJECTIVES: To examine the effect of aerobic exercise interventions on cardiopulmonary, immunologic and psychological parameters in adults living with HIV infection. SEARCH STRATEGY: Studies were identified using MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE CINAHL, HEALTHSTAR, PSYCHLIT, SOCIOFILE, SCI, SSCI, ERIC, DIA and abstracts from international AIDS meetings, ICAAC, and other major meetings. Reference lists from pertinent articles and books and personal contact with authors were also used, as were Collaborative Review Group databases and results of hand searching of targeted journals. All languages were included. Searches covered the period from 1980 to July 1999. SELECTION CRITERIA: For inclusion, studies had to be randomized control trials involving HIV+ adults 18 years of age or older and had to include at least one group randomized to receive aerobic exercise performed at least three times/week for at least four weeks. DATA COLLECTION AND ANALYSIS: Data on study design, participants, interventions, and outcomes were extracted from the reports onto specifically designed data collection forms by at least two reviewers. MAIN RESULTS: Six studies satisfied the eligibility criteria. The main results indicated that performing constant or interval aerobic exercise for at least 20 minutes, at least three times per week for four weeks may lead to increased CD4 count, improved cardiopulmonary fitness, and improved psychological status. These findings are limited to those who continued to exercise and for whom there was adequate follow-up data. REVIEWER'S CONCLUSIONS: Aerobic exercise appears to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small sample sizes and large drop-out rates of the included studies. Further research is required to determine the optimal parameters of aerobic exercise and stage of disease in which aerobic exercise may be most beneficial for adults living with HIV infection.

Ovine metabolism of saponins: evaluation of a method for estimating the ovine uptake of steroidal saponins from Narthecium ossifragum.

A sheep was dosed three times per day over six consecutive days with 70 g Narthecium ossifragum, and once on the seventh day with 70 g N. ossifragum. Additionally, it was dosed once on days 1-7 with 20 mg of [20,23,23-2H3]sarsasapogenin. After 7 days, the sheep was killed and GC-MS analysis of the free and conjugated sapogenin content in bile, urine, rumen, duodenum, jejunum, colon and rectum samples collected from the sheep, faecal samples collected on days 4-7, and dosed plant material was performed. The N. ossifragum contained mainly sarsasapogenin and smilagenin. Only neglible levels of deuterium-labelled sarsasapogenins were detected in the samples from the animal. Ingested saponins were quickly hydrolysed in the rumen to free sapogenins and, in part, epimerized at C-3 to afford episapogenins. The absorption of free sapogenins appeared to occur in the jejunum. The concentration of sapogenins in faeces reached a plateau 108 h after dosing started.

Diglucosylation of salicyl alcohol by cell suspension cultures of Solanum laciniatum.

A new biotransformation product, salicyl alcohol-7-O-beta-D-(beta-1,6-D-glucopyranosyl)-gluco-pyranoside was isolated from cell suspension cultures of Solanum laciniatum, following administration of salicyl alcohol, and its structure was elucidated using a combination of one- and two-dimensional 1H and 13C-NMR data, and positive and negative ion ESMS data.

Tolerance to the nephrotoxic component of Narthecium ossifragum in sheep: the effects of repeated oral doses of plant extracts.

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 micromol/L to between 260 and 510 micromol/L. The serum urea concentrations increased from about 5-8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5-30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 micromol/L to 300-760 micromol/L, and urea concentrations from 5-8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.

Improvements following short term home based physical therapy are maintained at one year in people with moderate to severe rheumatoid arthritis.

OBJECTIVE: We previously demonstrated the efficacy of a 6 week home based physical therapy (PT) intervention for people with moderate to severe rheumatoid arthritis (RA). This followup study determined if short term improvements were maintained to one year. METHODS: Participants in the short term study were randomly assigned to receive a PT intervention (education, exercise, and pain relief modalities) delivered by physiotherapists with advanced rheumatology training (Weeks 0 to 6) or to a wait list control group. The control group received the intervention between Weeks 6 to 12. Outcome measures included the Stanford Arthritis Self-Efficacy Scale (SES), the Arthritis Community Research and Evaluation Unit Rheumatoid Arthritis Knowledge Questionnaire (KQ), and a visual analog scale for pain. Disease activity measures (tender joints, grip strength, and morning stiffness) were also included. MANOVA was used to compare within-subject scores at baseline and at 12 and 52 weeks. Paired t tests were used to determine if 12 week changes were maintained at 52 weeks. RESULTS: Of the 127 protocol completers, 117 (92.1%) were available for the one year followup. For those measures that showed significant improvement in the randomized controlled trial (SES, KQ, morning stiffness), improvements at 12 weeks were maintained at 52 weeks (p > 0.010). CONCLUSION: Subjects who participated in a short term home based PT intervention delivered by specially trained therapists reported improved outcomes following treatment, and these improvements were maintained at one year followup. Future studies need to explore the relative contributions of education, exercise, home based care, therapist training, and reinforcement strategies in improving longterm outcomes in RA.