Search

Research showed a positive association between back fat (BF) change the week before farrowing and colostrum yield (CY). This study tested the causality of this association, hence to optimize CY by altering the sows' peripartal feeding strategy. Sows were randomly divided into 2 treatment groups at d 108 of gestation. The first group (L, n = 28) received 1.5 kg feed.d(-1), the second group (H, n = 22) received 3 times 1.5 kg feed.d(-1) until farrowing. Daily feed intake and CY were measured. Colostrum was analyzed for nutrient composition, AA and fatty acids, IgG and IgA. Sow serum was obtained at d 108 of gestation and d 1 of lactation after overnight fasting and analyzed for NEFA, (iso) butyrylcarnitine (C4), creatinine, urea, 3-OH-butyrylcarnitine (3-OH-C4), IgG, and IgA. Based on BF at d 108, sows were divided into body condition (BC) groups: skinny (23 mm, n = 14). We performed ANOVA with treatment and BC as fixed factors and Scheffe post-hoc test. The week before farrowing, the L group had the lowest daily feed intake (DFI; 1.5 kg), and within the H group, fat sows (3.8 kg) had a lower DFI than skinny sows (4.3 kg; p = 0.006). The H group tended to have a greater total CY (P = 0.074) and had a greater CY/kg liveborn piglet (P = 0.018) than the L group. Compared with sows in moderate BC, fat sows had a lower total CY (P = 0.044) and a lower CY/kg liveborn piglet (P = 0.005). The H group had a greater concentration of lactose (p = 0.009) and n-3 PUFA (p < 0.001) but a lower concentration of protein (p = 0.040) in colostrum than the L group. The concentration of IgG and IgA did not differ between treatment and BC groups. Serum parameters at d 108 were similar between the treatment groups and BC groups. At d 1, the H group mobilized less body fat (NEFA: p = 0.002) and protein (creatinine: p < 0.001, C4: p = 0.016) reserves but had a greater ratio urea: NEFA (p < 0.001) and less ketone bodies (3-OH-C4: p < 0.001) compared with the L group. This indicates a more balanced entry of metabolites in the citric acid cycle and thus a better support of the maternal peripartal metabolism in the H group. Serum parameters did not differ between BC groups. Both CY and composition can be influenced by the peripartal feeding strategy and BC. The highest CY and most beneficial colostrum composition were obtained when sows entered the farrowing unit in a moderate BC and were provided a high peripartal feeding strategy.

OBJECTIVE- To evaluate metabolic effects of sex steroids in nonfasting and fasting conditions, independent from changes in body composition. RESEARCH DESIGN AND METHODS- A randomized clinical trial was performed to create contrasting sex steroid levels in healthy young men: by letrozole (aromatase inhibitor) to lower estradiol (E-2) and increase testosterone (group T, n = 10) versus letrozole plus E-2 patches to lower T and raise E-2 (group E, n = 10). Mixed meals and hyperinsulinemic-euglycemic clamps were performed before and after a 1-week treatment period. RESULTS- Following intervention, the postprandial triglyceride response displayed a diverging response with a decline in group T and an increase in group E; the postprandial glucose-dependent insulinotropic polypeptide (GIP) response increased in group T. Insulin sensitivity increased in group T but remained unaltered in group E. CONCLUSIONS- In healthy young men, short-term changes in sex steroids affect postprandial triglyceride and GIP response and insulin sensitivity.

Background: Mutations in 12 different PEX genes, resulting in generalized defects of peroxisomal biogenesis (PBD), are the cause of the Zellweger spectrum. It is characterised by severe global neurologic involvement and variable systemic features, including death in infancy or early childhood. We report an 11-year-old boy of normal intelligence with spinocerebellar ataxia caused by a PBD. Case report: the patient presented with balance problems, worsening from age 5. He had ataxia, absent ankle reflexes, and reduced vibration sense. Paraclinical examinations showed cerebral atrophy, axonal motor neuropathy and posterior column dysfunction. Very)long)fatty acid levels and plasmalogens wee within the normal range, but phytanic acid, pristanic acid levels, bile acid intermediates and pipecolic acid were clearly increased. Dietary restriction of phytanic acid lowered plasma levels of phytanic and pristanic acid and stabilized ataxia. Methods: Different peroxisomal enzymes were evaluated in cultured skin fibroblasts. Immunofluorescence studies for catalase were performed in cultured skin fibroblasts. Candidate PEX genes wee sequenced. Cultured fibroblasts were transfected with PEX10. Results: Analysis of peroxisomal enzymes revealed no clear abnormalities. Immunofluorescence studies showed peroxisomal mosaicism. Two mutations in PEX10 were found, c.764_765insA and R331Q. Transfection with PEX10 resulted in normal peroxisome formation, confirming that defective PEX10 caused the PBD. Discussion: The mild clinical and biochemical involvement in our patient is unusual for a PBD. Spinocerebellar ataxia without mental retardation caused by mutations in PEX10 has not been reported before. The evolution after dietary measures suggests this peroxisomal form of spinocerebellar ataxia may be partially treatable.

Mutations in cilium proteins polycystin 1 and 2 are linked to polycystic diseases in kidney and liver. In rats bile duct cells possess a single cilium; its mechanostimulation by bile flow increases intracellular Ca++ and lowers cAMP that drives HCO3 secretion (Masyuk, 2006). In contrast human liver has no ciliated bile ducts, except for a single report (Yoshino, 1979) not confirmed by others. We report the presence of multiple cilia on intralobular bile duct cells in the liver of a 1 m old girl born to non-consanguinous W-European parents. Her head circumference was below the 3rd P for her age and she showed minor facial dysmorphia, major hypotonia, increased liver enzymes and hypoglycemia. A Zellweger syndrome was suggested by strongly increased VLCFA and cortical renal cysts. Further work-up revealed abnormal ABR with a threshold of 80db. The baby died at 3.5 m in status epilepticus. Standard microscopy of the liver was unremarkable, but immuno-localisation of catalase and AGT showed staining in the parenchymal cytoplasm instead of in granules. By electron microscopy no peroxisome-like organelles were found; macrophage lysosomes contained typical but small trilamellar inclusions, and insoluble lipid. The lumen of 9/11 interlobular bile ducts in different blocks of a surgical biopsy sample demonstrated multiple cilia in addition to normal microvilli. Cilia were incomplete, for ex. single tubuli instead of doublets. In bile ducts of 5 out of 6 other Zellweger livers we did not observe cilia. We propose that ciliated cells reflect a partial transdifferentiation likely related to specific mutations.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease, due to deficient arylsulfatase A. There is no curative treatment except for early allogeneic hematopoietic stem cell transplantation. We present data on 4 patients with juvenile MLD. Three had a P426L mutation and one patient was homozygous for a C156T mutation. The clinical picture was similar including onset around 15-17 years with behavioural changes, desinhibition, followed by memory dysfunction and spastic paraparesis and polyneuropathy. The first patient was diagnosed at the age of 19 years and had already extensive cerebral white matter involvement. His younger sister (15 years) at the time of diagnosis was still asymptomatic. Both siblings had no HLA-identical or acceptable HLA-matched unrelated marrow or blood cell donor. They were both transplanted using each two unrelated umbilical cord blood units. The 19-year old patient had a follow-up of 6 months after transplant, has full donor chimerism, full haematological recovery and is neurologically stable. The third patient was diagnosed at the age of 18 years with cognitive decline and psychiatric symptoms. She had a HLA-identical unaffected sister and underwent peripheral blood cell stem transplantation (with reduced intensity conditioning) successfully. She stabilized neurologically. The fourth patient diagnosed at 20 years, had a HLA-identical unaffected brother and was treated likewise, at 22 years. She obtained stable mixed blood cell chemirism but the disease was progressive, despite donor lymphocyte infusions to improve the level of chimerism. The arylsulfatase levels of the first three patients is still short to draw definitive conclusions. It is suggested that allogeneic hematopoietic stem cell transplantation is feasible in juvenile MLD and that treatment at an early stage is more likely to be beneficial.