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Formalin-fixed lung tissue and paraffin blocks containing peripheral lung tissue obtained from subjects with an occupational asbestos exposure are both regarded to be suitable to determine asbestos load. Because sample preparation of paraffin blocks requires a more intense treatment than formalin-fixed tissue, we tested whether asbestos analysis of formalin-fixed lung tissue and paraffin blocks obtained from the same patients deliver comparable results.We determined numbers of asbestos bodies (AB) and amphibole asbestos fibers (AF) in formalin-fixed lung tissue and corresponding paraffin blocks from 36 patients. For AB counts, samples were digested in sodium hypochlorite. For AF analysis, tissue was freeze-dried and then ashed. Results were reported as numbers of AB and AF per gram dry lung tissue.Both AB counts as well as AF counts were lower in paraffin blocks than formalin-fixed lung tissue. Compared to formalin-fixed tissue, the limit of detection was higher for paraffin blocks, rendering more results from paraffin blocks not interpretable than from formalin-fixed tissue (8 samples versus 1 for AB and 15 samples versus 4 for AF).Asbestos analysis of paraffin blocks may lead to underestimation of asbestos exposure. This should be considered when assessing occupational asbestos exposure through lung dust analysis in medico-legal evaluation.

To compare the effects of a high-calcium vitamin D-fortified milk with added FOS-inulin versus regular milk on serum parathyroid hormone, and bone turnover markers in premenopausal (Pre-M) and postmenopausal (PM) women over 12 weeks. Premenopausal women (n = 136, mean age 41 (±5) years) and postmenopausal women [n = 121, mean age 59 (±4) years] were recruited, and each age group randomised into two groups to take two glasses per day of control = regular milk (500 mg calcium per day) or intervention (Int) = fortified milk (1000 mg calcium for pre-M women and 1200 mg calcium for PM women, 96 mg magnesium, 2.4 mg zinc, 15 µg vitamin D, 4 g FOS-inulin per day). At baseline, week 4 and week 12 serum minerals and bone biochemical markers were measured and bone density was measured at baseline. Mean 25-hydroxyvitamin D [25(OH) vitamin D3] levels among groups were between 49 and 65 nmol/L at baseline, and over the 12 weeks of supplementation, the fortified milk improved vitamin D status in both Int groups. CTx-1 and PINP reduced significantly in both Pre-M and PM groups over the 12 weeks, with the changes in CTx-1 being significantly different (P

In Malaysia, hip fracture incidence is higher in Chinese women than other ethnic groups. This study compared the effects of a high-calcium vitamin D fortified milk with added FOS-inulin versus regular milk over 1 year on aspects of bone health in Chinese postmenopausal women in Malaysia. One-hundred and twenty-one women (mean age 59 (± 4) years) were randomized into two groups: control (n = 60; regular milk, 428 mg calcium per day) or intervention (n = 61; fortified milk at 1200 mg calcium, 96 mg magnesium, 2.4 mg zinc, 15 μg vitamin D and 4 g FOS-inulin per day). At baseline, weeks 12, 24, 36 and 52, parathyroid hormone (PTH), C-Telopeptide of Type I Collagen (CTx-1), Procollagen I Intact N-Terminal propeptide (PINP) and vitamin D levels were assessed. Bone density (BMD) was measured at baseline and week 52 using a GE Lunar iDXA. Body mass index, lumbar spine and femoral neck BMD did not differ between groups at baseline. Over 52 weeks, mean plasma 25 (OH) D3 levels increased to 74.8 nmol/L (intervention group) or remained at 63.1 nmol/L (control group) (p

Risk for developing osteoporosis increases in Asia. The purpose of the study was to evaluate the impact of a high-calcium vitamin D fortified milk (HCM) intervention on parathyroid hormone (PTH) levels, vitamin D status and markers of bone turnover in postmenopausal Chinese women.Sixty three women (55 years) were assigned to receive two servings of either a calcium/vitamin D fortified milk or a control drink for 12 weeks. PTH, serum 25 (OH)D levels, C-telopeptide of type I collagen (CTX) levels and procollagen type I N-terminal propeptide (PINP) were measured at baseline, 2, 8 and 12 weeks of supplementation.Daily calcium intake at baseline ranged between 260 and 482 mg for the HCM, and 252 and 692 mg for the control group. HCM improved serum 25 (OH)D levels significantly (33.13-39.49 nmol/l), while remaining similar in the control group (29.27-28.21 nmol/l). The difference between the groups were significant at week 2, 8 and 12. The percentage change in PTH levels in the HCM group was significant from week 2 onwards compared to the control drink (P0.017, P0.05 and P0.001 at weeks 2, 8 and 12, respectively). Plasma CTX of the HCM group reduced by 25% between weeks 0 and 2, remaining significantly lower and at similar levels up to week 12. The difference between the HCM and control group for PINP reached significance at weeks 8 (P=0.011) and 12 (P=0.003).The HCM intervention significantly improved vitamin D status and reduced bone turnover over 12 weeks in postmenopausal Chinese women.

Objectives Previous laboratory studies have identified two dairy fractions, glycomacropeptide (GMP) and G600 milk fat extract (G600), with anti-inflammatory effects in models of acute gout. The aim of this proof-of-concept clinical trial was to test the hypothesis that daily intake of skim milk powder (SMP) enriched with GMP and G600 can prevent gout flares. Methods This was a 3-month randomised double-blind controlled trial of milk products for prevention of gout flares. One hundred and twenty patients with recurrent gout flares were randomised to one of three arms: lactose powder control, SMP control and SMP enriched with GMP and G600 (SMP/GMP/G600). The primary end point was change in the frequency of gout flares using a daily flare diary measured monthly for 3 months. Results The frequency of gout flares reduced in all three groups over the 3-month study period compared with baseline. Over the 3-month study period there was a significantly greater reduction in gout flares in the SMP/GMP/G600 group (analysis of covariance p group =0.031, Tukey post hoc test compared with lactose control, p=0.044). Following treatment with SMP/GMP/G600 over the 3-month period, greater improvements were also observed in pain and fractional excretion of uric acid, with trends to greater improvement in tender joint count. Similar adverse event rates and discontinuation rates were observed between the three groups. Conclusions This is the first reported controlled trial of dietary intervention in patients with gout, and suggests that SMP enriched with GMP and G600 may reduce the frequency of gout flares.

Milk fat is a natural product containing essential nutrients as well as fatty acids and other food factors with reported anti-cancer potential. Here bovine milk fat was tested for its ability to inhibit the growth of breast and colon cancers and their metastasis to the lung and liver; either alone or in combination with the chemotherapeutic agent paclitaxel. A diet containing 5% typical anhydrous milk fat (representing ~70% of the total dietary fat component) fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26 colon cancer tumours and inhibited their metastasis to the lung and liver, when compared to the control diet containing soybean oil as the only fat component. It augmented the inhibitory effects of paclitaxel on tumour growth and metastasis, and reduced the microvessel density of tumours. It displayed no apparent organ toxicity, but instead was beneficial for well-being of tumour-bearing mice by maintaining gastrocnemius muscle and epididymal adipose tissue that were otherwise depleted by cachexia. The milk fat diet ameliorated gut damage caused by paclitaxel in non-tumour-bearing mice, as evidenced by retention of jejunal morphology, villi length and intestinal γ-glutamyl transpeptidase activity, and inhibition of crypt apoptosis. It prevented loss of red and white blood cells due to both cancer-mediated immunosuppression and the cytotoxic effects of chemotherapy. The present study warrants the use of milk fat as an adjuvant to inhibit tumour metastasis during cancer chemotherapy, and to spare patients from the debilitating side-effects of cytotoxic drugs.

Acute doses of Ca rapidly increase serum Ca and reduce bone resorption concomitant with a reduction in serum parathyroid hormone (PTH) levels. The physiological response to a dose of Ca in milk and to a Ca salt may be different. The present study investigated Ca absorption patterns with increasing levels of fortification in milk, and the response to one dose of a Ca salt. A group of twenty-eight Asian women aged 20–45 years volunteered to attend the laboratory over several weeks. The fasted volunteers were randomised to one of three experimental drinks: 200 ml skimmed milk containing 250, 500 or 1000 mg Ca. A subgroup of seven volunteers also received a calcium gluconate/carbonate salt containing 1000 mg Ca in 200 ml water. Serial blood samples and urine were collected for 5 h from baseline. Different doses of Ca in milk resulted in a graded response in serum corrected Ca, PTH and C-telopeptide of type I collagen (CTx) but not ionised Ca. Serum Ca increased in response to all milk drinks and from 2 to 5 h the blood Ca levels were significantly different for the 250 and 1000 mg doses, as was the integrated response between the loads. The PTH response to the two higher doses was significantly more than following the 250 mg dose. The integrated response for CTx and urinary Ca between all three doses of Ca in milk was significantly different. A dose of Ca salt elicited a more immediate response reaching a plateau faster, and declining faster to baseline. Fortified milk is a safe matrix for delivering larger doses of Ca.

Objective To assess the effects of tocilizumab on methotrexate and 7-hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a marker of inflammation. Methods Methotrexate (10 - 25 mg) was administered orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg tocilizumab intravenously. Blood samples for pharmacokinetic analyses were collected on Days 1, 15, and 43 and for pharmacodynamics (CRP) throughout the study. Results 90% CIs for mean effect ratios (Day 15/Day 1 and Day 43/Day 1) of methotrexate and 7-hydroxymethotrexate (AUClast and Cmax) were close to or within the bioequivalence boundaries (80 - 125%). CRP normalized within 1 week after tocilizumab injection and remained within normal limits for 3 weeks. Conclusion Tocilizumab and methotrexate can be administered concurrently without dosage adjustments.

Calcium and vitamin D are essential for bone growth; milk is an appropriate vehicle to be fortified with calcium, vitamin D and other minerals. The purpose of the current study was to compare the effect of supplementing with a high calcium milk drink with added vitamin D, magnesium and zinc (HCM) versus a placebo drink on serum parathyroid hormone (PTH) and vitamin D status as well as markers of bone formation/resorption in postmenopausal women living in South East Asia (Jakarta, Indonesia and Manila, the Philippines) over a period of 4 months. Calcium intake at baseline was 237 mg (median; 176-316, interquartile range) for Indonesia and 353 mg (median; 222-480, interquartile range) for the Filipino women per day. Fortified milk supplementation reduced the percentage of women that were insufficient in 25 (OH) vitamin D(3) (50 nmol/L) from 70% to 22% in the Indonesian women and 20% to 0% in the Filipino women. Fortified milk supplementation significantly reduced parathyroid hormone levels (PTH) by week 2 (22% and 11%), C-telopeptide of type I collagen (CTX) by week 2 (34% and 27%), osteocalcin (OC) by week 8 (18% and 25%) and procollagen type I N-propeptide (PINP) by week 8 (15% and 21%), in women from Indonesia and the Philippines, respectively. Thus, the HCM intervention was able to significantly improve vitamin D status, lower PTH levels and reduce bone turnover in two groups of South East Asian women.

Heat-induced gelation (80 degrees C for 30 min or 85 degrees C for 60 min) of whey protein concentrate (WPC) solutions was studied using small deformation dynamic rheology, small and large deformation compression, and polyacrylamide gel electrophoresis (PAGE). The WPC solutions (15% w/w, pH 6.9) were prepared by dispersing WPC powder in water (control), 1% (w/w) sodium dodecyl sulfate (SDS) solution, and N-ethylmaleimide (NEM) solution at a protein/NEM molar ratio of 1:1 or in 10 mM dithiothreitol (DTT) solution. PAGE analyses showed that the heat treatment of control solutions contained both disulfide and non-covalent linkages between denatured protein molecules. Only disulfide linkages were formed in heated SDS-WPC solutions, whereas only non-covalent linkages were formed in DTT-WPC and NEM-WPC solutions during heating. In heated NEM-WPC solutions, the pre-existing disulfide linkages remained unaltered. Small deformation rheology measurements showed that the storage modulus (G') values, compared with those of the control WPC gels (approximately 14000 Pa), were 3 times less for the SDS-WPC gels (approximately 4000 Pa), double for the NEM-WPC gels (approximately 24000 Pa), and even higher for the DTT-WPC gels (approximately 30000 Pa). Compression tests suggested that the rubberiness (fracture strain) of the WPC gels increased as the degree of disulfide linkages within the gels increased, whereas the stiffness (modulus) of the gels increased as the degree of non-covalent associations among the denatured protein molecules increased.

Milk is potentially beneficial for bone health, particularly for Chinese populations where consumption of dairy products is low. There are few data about milk consumption by Chinese women aged 20-35 years. This study examines whether milk supplement over 2 years caused increased bone mineral density (BMD) in Chinese women aged 20-35 years.Four hundred forty-one community-living women living in Hong Kong SAR (221) and Beijing (220) China were randomized to receive milk supplement or nothing. The supplement consisted of two sachets of milk powder (1000 mg calcium, 80 microg vitamin K(1)), for 24 months. BMD at total hip, total spine, and whole body was measured at baseline and at 6, 12, 18, and 24 months; blood specimens were analyzed at baseline and at 3 and 24 months for biochemical indices of bone turnover and vitamin K. Urine samples also were collected. Analysis was by intention to treat as well as per protocol. Differences in change from baseline between the milk and control groups were analyzed using the mixed models approach to repeated measures, including the baseline value as a covariate.Both groups had an increase in BMD and a decrease in bone turnover markers over time, as an indicator of the process of attainment of peak bone mass during this period. Apart from a higher total spine BMD at 6 months in the milk group using per protocol analysis, there was little significant difference observed between the milk group and the control group.Age-related bone metabolism and lack of compliance most likely explain the lack of consistent changes in BMD or bone biochemical measures in response to milk supplementation for 2 years in Chinese women aged 20-35 years.

We compared the effect of supplementation with a fortified skimmed milk product (high calcium skim milk) with or without added phylloquinone (vitamin K(1)) on markers of bone formation and resorption in premenopausal women.Eighty-two women 20 to 35 y of age were randomly allocated to three groups. Two groups received two daily servings of high calcium skim milk (1000 mg/d of extra calcium) with or without added phylloquinone (80 microg/d) for 16 wk, and a third control group received no supplementation. Bone density was assessed at baseline and the bone markers, total osteocalcin, type I N-terminal procollagen peptide, and cross-linked C-telopeptide of type I collagen were measured at baseline and at weeks 2, 12, and 16. Serum phylloquinone and undercarboxylated osteocalcin were measured in the control and vitamin K-supplemented groups at weeks 0 and 16.Baseline values for age, body mass index, and bone density did not differ across groups. In vitamin K-supplemented women, mean serum phylloquinone concentrations increased from 0.27 to 0.76 microg/L (P0.05) and undercarboxylated osteocalcin concentrations decreased from 9.68 to 4.46 microg/L (P0.05) over 16 wk. Plasma cross-linked C-telopeptide of type I collagen, total osteocalcin, and type I N-terminal procollagen peptide levels decreased significantly in both supplemented groups compared with the control group over 16 wk (cross-linked C-telopeptide of type I collagen30%, total osteocalcin and type I N-terminal procollagen peptide15%).Fortified milk supplementation in premenopausal women reduced bone turnover significantly. Phylloquinone fortification substantially improved vitamin K status but had no demonstrable additive effect on bone turnover in this short-term study.