Management of craniosynostosis

Learning Objectives: After studying this article, the participant should be able to: 1. Review the etiopathogenesis of craniosynostosis and craniofacial anomalies. 2. Develop a basic understanding of the clinical manifestations and diagnosis of craniofacial anomalies. 3. Describe the surgical principles of managing craniosynostosis and craniofacial anomalies.Craniosynostosis, or the premature closure of calvarial sutures, results in deformed calvaria at birth. Although the etiology of craniosynostosis is currently unknown, animal experiments and a recent interest in molecular biology point toward interplay between the dura and the underlying brain. This interaction occurs by means of a local alteration in the expression of transforming growth factor, MSX2, fibroblast growth factor receptor, and TWIST. The fused suture restricts growth of the calvaria, thus leading to a characteristic deformation, each associated with a different type of craniosynostosis. Uncorrected craniosynostosis leads to a continuing progression of the deformity, and in some cases, an elevation of intracranial pressure. Clinical examination should include not only an examination of the skull but also a general examination to rule out the craniofacial syndromes that accompany craniosynostosis. Because deformational plagiocephaly, or plagiocephaly without synostosis, occurs secondary to sleeping in the supine position during the early perinatal period, the physician should be aware of this abnormality. Treatment for deformational plagiocephaly is conservative when compared with treatment for craniosynostosis, which requires surgery. Appropriate investigations should include genetic screening, radiologic examination with a computerized tomographic scan, and neurodevelopmental analysis. Surgical intervention should be performed during infancy, preferably in the first 6 months of postnatal life, to prevent the further progression of the deformity and possible complications associated with increased intracranial pressure. The principles of surgical intervention are not only to excise the fused suture but also to attempt to normalize the calvarial shape. Long-term follow-up is critical to determine the effect of the surgical outcome.     

Effects of land irrigation with partially-treated wastewater on Frankia survival and infectivity

Phytoextraction of Cd by some populations of Thlaspi caerulescens which have the ability to co-hyperaccumulate Cd and Zn requires information about the distribution of both metals within the plant at the organ-level. This work was conducted to determine whether the distribution and solubility of Cd and Zn in Thlaspi caerulescens are affected by the age of plant and organ, and whether Cd and Zn have a common distribution in the plant in soils contaminated by both metals. A series of pot experiments were conducted where a Cd- and Zn-hyperaccumulating population was grown on soils contaminated by Cd and Zn. Temporal changes in metal concentration of roots and of shoots was recorded, along with the water and CaCl₂ solubility of metals in the plant organs. Also, leaves were grouped according to their age and their respective content of Cd and Zn was measured. Both metals were present at higher concentrations in leaves than in roots. The whole-plant content of Zn decreased with time while that of Cd increased or remained unchanged. At harvest, young leaves exhibited higher Cd concentration than older, but the reverse was true for Zn. Both metals were more soluble in dry leaves and senescent leaves than in fresh material, and Zn was more water-soluble than Cd. In conclusion, the distribution of Cd and Zn in the hyperaccumulator T. caerulescensvaried according to the organ and plant age, and Cd and Zn were shown to have a different distribution within the plant.     

Protective effects of antioxidants on age-related changes in the electrophoretic patterns of cardiac LDH,hepatic ALP and serum proteins in male golden hamster

Basal and antioxidant-induced changes in the isoenzyme and isoform patterns of cardiac lactate dehydrogenase (EC 1.1.1.27) and hepatic alkaline phosphatase (EC 3.1.3.1), respectively, as well as the electrophoretic patterns of serum proteins in different age groups of male golden hamster were compared. This is to test whether age-induced changes could be corrected by long-term administration of antioxidants. Data indicated that aging causes no remarkable change in the total activity of either cardiac LDH or hepatic ALP, however a significant increase in the fractional activity of some cardiac LDH isoenzymes and a significant reduction in the fractional activity of some hepatic ALP isoforms were induced by aging. On the other hand, long-term administration of antioxidants appeared to manifest a clear counteracting effect on the age-related changes in old age. This effect was indicated in the fractional activity of cardiac LDH isoenzymes and of hepatic ALP isoforms. The present study has also shown a wide-range variation in serum protein patterns due to aging and/or antioxidant administration, which indirectly reflect a parallel variation in the process of gene expression and/or proteolytic activity.     

The phototoxicity of phenothiazinium derivatives against Escherichia coli and Staphylococcus aureus

Phenothiazinium dyes, and derivatives, were tested for toxicity to Escherichia coli and Staphylococcus aureus. The dyes were generally lipophilic (log P>1) and showed inherent dark toxicity (minimum lethal concentrations: 3.1-1000 microM). Dye illumination (total light dose of 3.15 J cm(-1) over 30 min) led to up to eight-fold reductions in minimum lethal concentrations. Most of the illuminated dyes showed significant relative singlet oxygen yields (phi'delta: 0.18-1.35) suggesting a type II mechanism of generating a phototoxic response. Although generally up to six-fold more effective against S. aureus, the dyes tested efficiently killed E. coli and may be of particular use in combating Gram-negative pathogens.     

Comparative evaluation of D-glucosyl thiouronium, glucosylthio heterocycles, Daonil, and insulin as inhibitors for hepatic glycosidases

Comparison of the in vivo and in vitro effects of S-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)thiuronium bromide (1), 2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylthio-1,3,4-thiadiazolin-5-thione (2), and 2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylthio)-1,3-benzoxazole (3), as well as the antidiabetics Daonil and insulin on glycosidase enzymes has been investigated. Compound 1 inhibited both alpha- and beta-glucosidases, but the inhibition was more potent with the beta-enzyme. Compound 2 was found to be a weaker inhibitor of these enzymes, while compound 3 showed a slight apparent activation.     

A recombinant plant natriuretic peptide causes rapid and spatially differentiated K+, Na+ and H+ flux changes in Arabidopsis thaliana roots

Plant natriuretic peptides (PNPs) belong to a novel class of systemically mobile molecules that are structurally similar to the N-terminal domain of expansins and affect physiological processes such as protoplast volume regulation at nano-molar concentrations. Here we demonstrate that AtPNP-A, a recombinant Arabidopsis thaliana PNP causes rapid H(+) influx in the elongation zone of A. thaliana roots but not in the mature zone. AtPNP-A also induces significant K(+) and Na(+) efflux and this effect is seen in the mature root zone only. These observations suggest that responses to AtPNP-A are developmental stage and tissue specific and point to a complex role in plant growth and homeostasis.     

Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test

Increased glucose cycling between glucose and glucose-6-phosphate is characteristic of insulin resistance and hyperglycemia seen with Type II diabetes. Traditionally, glucose cycling is determined by the difference between hepatic glucose output measured with separate [2-3H]glucose and [6-3H]glucose infusions. We demonstrate a novel method for determining hepatic glucose recycling from an intraperitoneal glucose tolerance test (IPGTT). A single tracer, [1, 2-13C(2)]glucose (a M2 glucose isotopomer), was administered at 1mg/g body weight to 4-month-old C57BL/6 mice. Hepatic glucose recycling was monitored by the appearance of a plasma M1 isotopomer of glucose, which is produced by the action of the pentose cycle on the M2 glucose isotopomer in the liver. The initial M2 enrichment was 56% and decreased to 13% at the end of 3 h, and the M1 enrichment peaked at 2 h. The ratio of plasma M1/M2 glucose increased linearly with time to approximately 25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant k(HR). k(HR) estimates glucose/glucose-6-phosphate futile cycling, along with glucose recycling through the pentose cycle. These observations demonstrate complex substrate cycling during an IPGTT using a single stable isotope tracer.     

Local variation in helminth burdens of Egyptian spiny mice (Acomys cahirinus dimidiatus) from ecologically similar sites: relationships with hormone concentrations and social behaviour

Populations of Egyptian spiny mice (Acomys cahirinus dimidiatus) in a fragmented montane wadi system in the Sinai showed significant differences in the abundance of gut helminths. Differences in parasite load between populations were positively associated with measures of androgen activity but showed no significant relationship with glucocorticoid activity. Social discrimination tests with adult males from different wadis showed that those from sites with greater helminth abundance were less likely to investigate odours from other males and were less aggressive when subsequently interacting with the odour donors. Subjects showed markedly more investigation towards the odours of males from distant wadis compared with those from their own or immediately neighbouring wadi, but were less aggressive when confronted with odour donors from distant wadis. Despite this, there was a positive relationship between the amount of investigation towards distant male odour and subsequent aggression towards the male. While aggressiveness was positively associated with measures of androgen and glucocorticoid activity, no significant relationship emerged with individual helminth infection. Thus aggressiveness appeared to relate to overall local population levels of infection rather than individual challenge.     

Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo

The Duffy Ag expressed on RBCs, capillaries, and postcapillary venular endothelial cells binds selective CXC and CC chemokines with high affinity. Cells transfected with the Duffy Ag internalize but do not degrade chemokine ligand. It has been proposed that Duffy Ag transports chemokines across the endothelium. We hypothesized that Duffy Ag participates in the movement of chemokines across the endothelium and, by doing so, modifies neutrophil transmigration. We found that the Duffy Ag transfected into human endothelial cells facilitates movement of the radiolabeled CXC chemokine, growth related oncogene-alpha/CXC chemokine ligand 1 (GRO-alpha/CXCL1), across an endothelial monolayer. In addition, neutrophil migration toward GRO-alpha/CXCL1 and IL-8 (IL-8/CXCL8) was enhanced across an endothelial monolayer expressing the Duffy Ag. Furthermore, GRO-alpha/CXCL1 stimulation of endothelial cells expressing the Duffy Ag did not affect gene expression by oligonucleotide microarray analysis. These in vitro observations are supported by the finding that IL-8/CXCL8-driven neutrophil recruitment into the lungs was markedly attenuated in transgenic mice lacking the Duffy Ag. We conclude that Duffy Ag has a role in enhancing leukocyte recruitment to sites of inflammation by facilitating movement of chemokines across the endothelium.     

Composition of<Emphasis Type="Italic">Casuarina</Emphasis> leaf litter and its influence on<Emphasis Type="Italic">Frankia-Casuarina</Emphasis> symbiosis in soil

Plant needles ofCasuarina equisetifolia were collected and analyzed in parallel with soil analysis. In three strains ofFrankia—symbionts ofCasuarina—their infectivity and plant performance was determinedin vitro after soil amendment with different leaf litter concentrations. Only one strain was able to nodulate the plant at all litter concentrations (0.5, 3 and 5%) although the nodules were very small. However, all treated plants grew poorly; their growth was reduced by approximately 90% (for 5% litter concentration) compared to plants grown on untreated soil, on the basis of total dry mass. Inhibition of nodulation can be attributed to high concentrations of some elements and compounds that were either found inC. equisetifolia litter or originally found in soil (i.e. chloride, cyanide, copper, manganese and phenols). In general, plant growth decreased as more litter was added. Plant total nitrogen content was also reduced after increasing the litter concentration. The inhibitory effect of high litter concentrations was mainly on plant growth and to a lesser extent on plant nodulation byFrankia strains.