Bile acids and bile alcohols in a child with hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency: effects of chenodeoxycholic acid treatment

Duodenal bile, urine, plasma, and feces from a child with hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency were analyzed by fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry to investigate the formation and excretion of abnormal bile acids and bile alcohols. The biliary bile salts consisted of glycocholic acid (25%) and of sulfated and glycine conjugated di- and trihydroxycholenoic acids (55%), two C27 bile acids, and eleven sulfated bile alcohols (mainly tetrols, 20%), all having 3 beta,7 alpha-dihydroxy-delta 5 or 3 beta,7 alpha,12 alpha-trihydroxy-delta 5 ring structures. In plasma, sulfated cholenoic acids constituted 65% and unconjugated 3 beta,7 alpha-dihydroxy-5-cholestenoic acid 25% of the total level, 71 micrograms/ml. The urinary excretion of the former was 30.4 mg/day and that of unsaturated bile alcohol sulfates, mainly pentols, 7 mg/day. The predominant bile acid in feces was an unconjugated epimer of 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid, and small amounts of cholic acid were present. The minimum total excretion was 11.3 mg/day. Treatment with chenodeoxycholic acid resulted in marked clinical improvement and normalized liver function tests. Further studies are needed to define the mechanism of action. Plasma bile acids decreased to 1.6 micrograms/ml and urinary excretion to 3.4 mg/day. Chenodeoxycholic and ursodeoxycholic acids became predominant in all samples. The fecal excretion of unsaturated cholenoic acid sulfates increased to 40 mg/day compared to 89 mg/day of saturated bile acids. The results provide further support for a defective hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency, and indicate that the 3 beta-hydroxy-delta 5 bile acids are formed via 7 alpha-hydroxycholesterol. The formation of glycocholic acid may be due to an incomplete enzyme defect or to transformation of the 3 beta-hydroxy-delta 5 structure by bacterial and hepatic enzymes during an enterohepatic circulation.     

A full body musculoskeletal model based on flexible multibody simulation approach utilised in bone strain analysis during human locomotion

Load-induced strains applied to bone can stimulate its development and adaptation. In order to quantify the incident strains within the skeleton, in vivo implementation of strain gauges on the surfaces of bone is typically used. However, in vivo strain measurements require invasive methodology that is challenging and limited to certain regions of superficial bones only such as the anterior surface of the tibia. Based on our previous study [Al Nazer et al. (2008) J Biomech. 41:1036–1043], an alternative numerical approach to analyse in vivo strains based on the flexible multibody simulation approach was proposed. The purpose of this study was to extend the idea of using the flexible multibody approach in the analysis of bone strains during physical activity through integrating the magnetic resonance imaging (MRI) technique within the framework. In order to investigate the reliability and validity of the proposed approach, a three-dimensional full body musculoskeletal model with a flexible tibia was used as a demonstration example. The model was used in a forward dynamics simulation in order to predict the tibial strains during walking on a level exercise. The flexible tibial model was developed using the actual geometry of human tibia, which was obtained from three-dimensional reconstruction of MRI. Motion capture data obtained from walking at constant velocity were used to drive the model during the inverse dynamics simulation in order to teach the muscles to reproduce the motion in the forward dynamics simulation. Based on the agreement between the literature-based in vivo strain measurements and the simulated strain results, it can be concluded that the flexible multibody approach enables reasonable predictions of bone strain in response to dynamic loading. The information obtained from the present approach can be useful in clinical applications including devising exercises to prevent bone fragility or to accelerate fracture healing.     

Direct in vivo strain measurements in human bone-a systematic literature review

Bone strain is the governing stimuli for the remodeling process necessary in the maintenance of bone's structure and mechanical strength. Strain gages are the gold standard and workhorses of human bone experimental strain analysis in vivo. The objective of this systematic literature review is to provide an overview for direct in vivo human bone strain measurement studies and place the strain results within context of current theories of bone remodeling (i.e. mechanostat theory). We employed a standardized search strategy without imposing any time restriction to find English language studies indexed in PubMed and Web of Science databases that measured human bone strain in vivo. Twenty-four studies met our final inclusion criteria. Seven human bones were subjected to strain measurements in vivo including medial tibia, second metatarsal, calcaneus, proximal femur, distal radius, lamina of vertebra and dental alveolar. Peak strain magnitude recorded was 9096 με on the medial tibia during basketball rebounding and the peak strain rate magnitude was -85,500 με/s recorded at the distal radius during forward fall from standing, landing on extended hands. The tibia was the most exposed site for in vivo strain measurements due to accessibility and being a common pathologic site of stress fracture in the lower extremity. This systematic review revealed that most of the strains measured in vivo in different bones were generally within the physiological loading zone defined by the mechanostat theory, which implies stimulation of functional adaptation necessary to maintain bone mechanical integrity.     

Potential predation of the exotic Amblyseius swirskii on Euseius concordis (Acari: Phytoseiidae), a predatory mite commonly found in Brazil

Intra/interspecific predation by A. swirskii.

Both Benin and Netherlands populations of Amblyseius swirskii engaged in cannibalism, and in predation on Euseius concordis larvae. Provision of pollen decreased cannibalism considerably, but had a smaller effect on predation on E. concordis. Potential effect of the eventual introduction of A. swirskii for control of Bemisia tabaci in Brazil is discussed.     

Biocontrol of broomrape using Fusarium oxysporum f. sp. orthoceras in tomato crops under field conditions

The effects of Fusarium oxysporum f. sp. orthoceras as a mycoherbicide on broomrape, a weedy parasite of tomato crops, were examined during two growing seasons under field conditions. In contrast to emerged broomrapes in treated plots, none of the tomato plants inoculated with fungal pathogen showed Fusarium-wilt symptoms. In 2008, both suspension concentrations, 1?×?10⁶ and 1?×?10⁷ spore/ml, used via either root-dip or soil-inoculation three weeks after transplanting, and high-concentration-soil-inoculation one week after transplanting, reduced the number of broomrape plant and shoots per plant compared to the control. In 2009, single-point-low-dose and twice-high-dose applications of sulfosulfuron had significantly fewer broomrape plants than high-concentration-soil-inoculation three weeks after transplanting. High-concentration-root-dip inoculation decreased broomrape biomass weight significantly by 58% compared to the control in 2008. In 2009, mean biomass for single-point-application of sulfosulfuron at 50 and 75?g levels was lower than control. The highest yield was detected in high-concentration-soil-inoculation at transplanting in 2008 and in low-dose-twice-application of sulfosulfuron in 2009. Tomato yield was associated with the number of broomrape shoots per plant. There is promise that these field-scale findings will improve attempts to use mycoherbicides for biocontrol of broomrapes in tomato cropping systems.     

No linkage to the 3β-HSD gene cluster in a kindred affected with 3β-hydroxy-Δ5-C27steroid dehydrogenase deficiency and early onset hepatic failure

We studied the segregation of the genes for 3-hydroxy-C_19/21-steroid dehydrogenase types I and II (3-HSD I and II) in a consanguineous family affected with 3-hydroxy-⁵-C₂₇steroid dehydrogenase (3-OH-C₂₇-SD) deficiency. The results show that the C₂₇ and C_19/21 steroid dehydrogenase activities are encoded by distinct genes that are not in genetic linkage. Further kindreds would assist in screening for linkage of 3-OH-C₂₇-SD to other members of the 3-hydroxysteroid dehydrogenase gene family.     

Segregation distortions of the ABO and Rh systems in malformed newborns

This study compares the segregation of the ABO and Rh systems between malformed newborns and a control group with two purposes: (1) to evaluate the participation of genetic factors associated with these blood groups in the production of congenital malformations, and (2) to prove, indirectly, the existence of reproductive losses associated with congenital malformations. The newborns and their mothers were typed for ABO and Rh groups. Gene frequencies were similar in malformed and control newborns. In the female malformed newborns, an excess of O-B pairs and a deficit of B-B pairs in the ABO system, and an excess of Rh(-)-Rh- pairs in the Rh system were found.     

Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly

Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. To analyze this prevalence in a South American population-based sample (57 HPE cases in 244,511 live and still births or 1 in 4300), we performed a mutational study of these genes in 30 unrelated children (26 newborns and 4 non-newborns) with HPE being ascertained by ECLAMC (Latin American Collaborative Study of Congenital Malformations). We identified three novel mutations: two were missense mutations of the SHH gene (Cys183-->Phe; His140-->Pro); the third mutation was a 2-bp deletion in the zinc-finger region of the ZIC2 gene. These molecular results explained 8% (2/26 newborn samples) of the HPE cases in this South American population-based sample, a proportion similar to our previously published data from a collection of cases.     

Morphological variation and reproductive incompatibility of three coconut-mite-associated populations of predatory mites identified as Neoseiulus paspalivorus (Acari: Phytoseiidae)

Predatory mites identified as Neoseiulus paspalivorus DeLeon (Phytoseiidae) have been considered as agents for classical biological control of the coconut mite, Aceria guerreronis Keifer (Eriophyidae), in Africa and elsewhere. Preliminary identification of geographically distinct populations as belonging to the same species (N. paspalivorus) was based on their morphological similarity. However, laboratory studies recently conducted have shown large differences in feeding behaviors and biological characteristics among individuals collected from three geographic origins: Brazil (South America), Benin and Ghana (West Africa). As morphologically similar specimens do not necessarily belong to the same species, we evaluated under laboratory conditions, reproductive compatibility between the specimens from three geographic locations to ascertain their conspecificity. Morphological measurements were also made to determine whether there is a means of discriminating between them. Inter-population crosses showed complete reproductive isolation between the three geographic populations, but interpopulation discontinuities in morphometric characters were absent. These results indicate that the tested specimens are distinct biological entities despite morphological similarity. Further molecular genetic studies are therefore proposed, including screening for endosymbionts and assessment of genetic differentiation, to determine the cause of reproductive incompatibility and to clarify the taxonomic relationship between those populations.