Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using analytical techniques, which included capillary column gas-liquid chromatography and mass spectrometry, detailed bile acid profiles were obtained for 24 fetal bile samples collected after legal abortions were performed between the 14th and 20th wk of gestation. Qualitatively, the bile acid profiles of all fetal bile samples were similar. The predominant bile acids identified were chenodeoxycholic and cholic acid. The presence of small but variable amounts of deoxycholic acid and traces of lithocholic acid suggested placental transfer of these bile acids from the maternal circulation. 3 beta-Hydroxy-5-cholenoic acid was detected at higher levels than lithocholic acid. A conspicuous feature of the profiles was the presence of bile acids with hydroxyl groups at positions C-1 and C-6, and one other nuclear position of unknown origin, indicating fetal hepatic synthesis via pathways different from those normally seen in the adult. Quantitatively total biliary bile acid concentrations were extremely low (less than 0.05 mM) before wk 17 of gestation, but thereafter concentrations markedly increased reflecting a possible surge in bile acid synthesis; however, the ratio of cholic:chenodeoxycholic acids remained relatively constant over this period (mean +/- SD = 0.85 +/- 0.36) and different from that reported for the healthy newborn (ca. 2.5) and adult (ca. 1.6). These data indicate an immaturity in hepatic 12 alpha-hydroxylation of bile acids during early development and may explain why other pathways, in particular 1 beta and 6 alpha-hydroxylation, are activated at this stage of life.
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PMID:Biliary bile acid composition of the human fetus in early gestation. 382 1

Further causes of rickets or osteomalacia need to be added to the list previously published by the author. These include phosphate deficiency osteomalacia from prolonged consumption of aluminum hydroxide, rickets and osteomalacia from prolonged therapy by antiepileptic drugs, rickets associated with the severe form of osteopetrosis, further rare causes of the Fanconi syndrome, congenital rickets occurring when the mother has osteomalacia from dietary causes or has celiac disease and temporary neonatal rickets probably due to enzymic immaturity. The importance is stressed of defining as closely as possible the type of rickets or osteomalacia one is dealing with, especially when considering therapy and detailed pathogenesis.
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PMID:Rickets and osteomalacia of various origins. 517 55

Experimental studies on the incubated egg, for example the embryo and the chorioallantoic membrane (CAM), are carried out frequently. The yolk-sac blood vessel system, the first system supplying the embryo, has not yet been used in toxicological studies. This paper describes experiments with ethanol and sodium hydroxide to test the application of this blood vessel system in the assessment of toxic effects. The experiments were carried out at day 4 of incubation. Different concentrations of the test substances were applied directly on yolk-sac. The acute reaction, mainly haemorrhages, was recorded semi-quantitatively up to 5 min post-application (p.a.). The results revealed a clear concentration dependency and marked differences between the two substances. During the late reaction up to 3 days p.a., repair processes occurred showing signs of a granulation tissue, including angiogenesis and the development of collagenous fibres. These experiments show the functional ability of the yolk-sac blood system for toxicological tests. Additionally, this system has some advantages compared with the CAM, for example the immaturity of the embryo nervous system and the possibility to evaluate findings on the embryo itself.
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PMID:The chick embryo yolk-sac blood vessel system as an experimental model for irritation and inflammation. 2070 89

We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic 26Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites: the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines.
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PMID:[Critical analysis of reference studies on aluminium-based adjuvants toxicokinetics]. 2857 61

We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. A single experimental study was carried out using isotopic 26Al (Flarend et al., Vaccine, 1997). This study used aluminum salts resembling those used in vaccines but ignored adjuvant uptake by cells that was not fully documented at the time. It was conducted over a short period of time (28days) and used only two rabbits per adjuvant. At the endpoint, Al elimination in the urine accounted for 6% for Al hydroxide and 22% for Al phosphate, both results being incompatible with rapid elimination of vaccine-derived Al in urine. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to an oral "minimal risk level" (MRL) extrapolated from animal studies. Keith et al. (Vaccine, 2002) used a high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (Vaccine, 2011) only considered solubilized Al, with erroneous calculations of absorption duration. Systemic Al particle diffusion and neuro-inflammatory potential were omitted. The MRL they used was both inappropriate (oral Al vs. injected adjuvant) and still too high (1mg/kg/d) regarding recent animal studies. Both paucity and serious weaknesses of reference studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including both neonatal and adult exposures, to ensure their safety and restore population confidence in Al-containing vaccines.
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PMID:Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants. 2930 41