Fetal tissue repair and wound healing

The fibrosis and scar formation that characterize adult wound healing are also the cause of clinical problems; scar contracture, hypertrophic scar, and pulmonary and hepatic fibrosis are only a few examples. Studies of fetal wound healing can provide an insight into the initiation and regulation of a scarless repair process akin to regeneration. Studies of fetal repair have already suggested mechanisms that might favorably alter adult healing. Topical application of hyaluronic acid to wounds in adult diabetic rats leads to enhanced epithelial migration. It has been recognized that the addition of TGF-beta to fetal wounds causes an adultlike healing response with fibrosis and inflammation. A subsequent study using neutralizing antibody to TGF-beta in adult wounds showed enhanced healing with a more normal dermal architecture with fewer macrophages, fewer blood vessels, and less collagen. As our understanding of regenerative tissue repair increases, the opportunities to modulate adult fibrotic conditions should expand.     

Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia

Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical features, the pathophysiology of PKD has remained unknown. The purpose of this study was to investigate the pathophysiology of idiopathic PKD by performing proton magnetic resonance spectroscopy (1H-MRS) in five patients with idiopathic PKD. Three patients were familial and two sporadic. Single-voxel 1H-MRS was performed on a GE 1.5-T SIGNA MR system. Localized 1H-MR spectra were obtained from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0 sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy; TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline, Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr in the unilateral basal ganglia was the only abnormality. In the remaining two, there was no significant abnormality. 1H-MR spectra obtained from the thalamus and SMA were all within normal limits. In conclusion, these results suggest that underlying pathophysiological mechanism of PKD may be at least partially associated with the dysfunction of cholinergic system in the basal ganglia.     

Energy intake and utilisation by nursing bearded seal (Erignathus barbatus) pups from Svalbard, Norway

In this study we measure energy intake via milk in nursing bearded seal (Erignathus barbatus) pups and determine how this energy is allocated into metabolism and storage of new tissues. This was accomplished using longitudinal mass gain records and the doubly labelled water technique on nursing pups in combination with cross-sectional data on changes in milk composition from bearded seal mothers. The pups (n = 3) were all less than a week old at the start of the experiments. Pups gained 3.3 +/- 0.4 kg.day-1 of which 50% was fat, 14% protein and 36% water. Average daily water influx for the pups was 69.5 +/- 9.0 ml.kg-1. day-1. Average CO2 production during the study period was 0.99 +/- 0.10 ml.g-1.h-1, which corresponds to a field metabolic rate of 642 +/- 67 kJ.kg-1. day-1, or 6.0 +/- 0.5 times the predicted basal metabolic rate according to Kleiber (1975). The pups drank an average of 7.6 +/- 0.5 kg of milk daily. This corresponds to a daily energy intake of 154 +/- 8 MJ, 47 +/- 14% of which was stored as new body tissue. Despite this high energy intake bearded seal pups do not get as fat as do other nursing phocids. This is in part due to their larger body size but also due to their very active aquatic lifestyle and the lower and more consistent fat content of the milk compared to other phocid species. Bearded seal mothers forage during lactation and may also be involved in teaching their pups to feed independently. All these data suggest that the lactation strategy of bearded seals differs from the phocid norm.     

Cross-linking of proteins by Maillard processes--model reactions of D-glucose or methylglyoxal with butylamine and guanidine derivatives

Advanced Maillard reaction in proteins leads to formation of covalently cross-linked aggregates the chemical nature of which is largely unknown. From model reactions of methylglyoxal and butylamine with creatine or alpha-N-acetyl-L-arginine, one main product each was isolated. These two compounds were identified, on the basis of unequivocal spectroscopic evidence, as 2-[(5-butylimino-4-methyl-4,5-dihydro-1H-2-imidazolyl)(methyl)amin o]acetic acid and 2-acetylamino-5-[(5-butylimino-4-methyl-4,5-dihydro-1H-2-imidazoly l)amino]pentanoic acid, respectively. Using D-glucose instead of methylglyoxal, two main products each were obtained from reaction with the respective guanidine derivative. The spectroscopic data definitively establish the formation of the diastereoisomeric 2-[(4-butyl-6,7-dihydroxy-4,5,6,7,8,8a-hexahydroimidazo[4,5-b]a zepin-2-yl)(methyl)amino]acetic acid from the reaction with creatine, and of the diastereoisomeric 2-acetylamino-5-[(4-butyl-6,7-dihydroxy-4,5,6,7,8,8a-hexahydroimidazo [4,5-b]azepin-2-yl)amino]pentanoic acid from the reaction with alpha-N-acetyl-L-arginine. All products were isolated in fairly good yield and represent 1:1:1 adducts of the respective reaction partners. Formation of these compounds thus constitutes an efficient reaction pathway for linking primary amines to guanidine derivatives. It seems justified, therefore, to expect cross-linking of proteins by action of reducing carbohydrates to proceed analogously.     

The growth of Malawian preschool children from different socioeconomic groups

Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences (Tarbp2-rs1, Tarbp2-rs2). The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells.     

Postcataract ptosis. A randomized, double-masked comparison of peribulbar and retrobulbar anesthesia

PURPOSE: A randomized, double-masked study of 317 patients was conducted to determine if the incidence of postcataract ptosis is greater with retrobulbar or two-injection peribulbar injection anesthesia. METHODS: Surgery consisted of a planned extracapsular extraction with posterior chamber lens implantation, and no superior rectus bridle suture was used. Ptosis was quantitatively documented preoperatively and postoperatively at 1, 2, 5, and 90 days by the surgeon, photographically at 90 days by a masked observer, and subjectively by the patients. Postcataract ptosis was defined as a drop in the lid margin of 2 mm or greater after correcting for any change in the fellow eye. RESULTS: The incidence of ptosis at 90 days in patients given peribulbar anesthesia was 5.8% and in patients given retrobulbar anesthesia 5.5%, and this difference was not statistically significant (P = 0.90). Eighteen percent of patients in both groups reported a change in the appearance of their eyelids. There was a moderate, positive correlation among patients who reported a change in their lid position and objective measurements of ptosis. Preoperative clinical measurements of vertical lid fissure width and levator function, and the appearance of the lid crease or superior sulcus were not predictive for the development of postoperative ptosis at 90 days; the best predictor was the presence of ptosis in the immediate postoperative period. CONCLUSION: The incidence of postcataract ptosis is the same whether two injection peribulbar or retrobulbar anesthesia is used.