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.     

Preparation and characterization of freeze-dried chitosan-poly(ethylene oxide) hydrogels for site-specific antibiotic delivery in the stomach

Sotos syndrome is included among the overgrowth disorders, most of which have an increased risk of neoplasms. Sotos syndrome does not appear to be related to a specific tumor type, but rather to the development of solid tumors of ectodermal or mesodermal origin in general. We report on two Sotos syndrome patients who developed a non-Hodgkin lymphoma and an acute lymphoblastic leukaemia, respectively. Our experience suggests that there may exist a high frequency of lymphoproliferative disorders in Sotos syndrome, and points out the importance of a long-term follow-up of Sotos syndrome patients, to detect a possible neoplastic evolution.     

Adverse drug reactions in pediatrics with a study of in-hospital intensive surveillance

A two-part prospective study of adverse drug reactions (ADRs) in Indian children was carried out at a teaching general hospital. Using an in-hospital intensive surveillance scheme (IISS) for the detection of ADRs, indoor patients of one of the two units in the pediatric ward were monitored daily for 6 months, with the other unit serving as a control group. A total of 347 patients were monitored, 2781 daily orders written and 24,474 doses of 96 different drugs given. Six patients suffered from ADRs (1.73%), and 1 reaction proved fatal (0.29%), while the control group reported only 1 ADR in the same time period. The frequency of ADRs (p < 0.001) and their resultant mortality in Indian children was less than that in a western prototype study. Though IISS showed a marked increase in ADR reporting, it was too cumbersome for routine use in our country. In the second part of the study, 40 cases of ADRs seen over 2 years were analyzed. Antimicrobials, especially sulphonamides, accounted for a high percentage of cases mostly as skin rashes and fairly severe reactions were common. Patients on anti-tuberculous and anti-convulsant drugs required prolonged supervision for late onset reactions.     

A role for cell migration in the sexual transmission of HIV-1?

The issue of how human immunodeficiency virus-1 (HIV-1) enters the body following sexual contact has been the subject of considerable controversy. Several possible routes for the initial infection have been suggested [1-6], including the possibility that the transmission is mediated by HIV-1-infected lymphocytes or macrophages in serum and female genital tract secretions, rather than by free virus. We recently reported that HIV-1-infected, activated primary monocytes can migrate between epithelial cells grown in confluent monolayer cultures in vitro [7]. We report here on experiments carried out in mice to test the hypothesis that mononuclear blood cells are capable of migrating through intact epithelia, and thus of carrying a virus into an animal. We placed double-stained, activated mononuclear blood cells into the vaginas of mice; four hours later, numerous double-stained cells were observed in the connective tissue beneath the vaginal epithelium and the iliac lymph nodes of the experimental mice. We speculate that such migration may be involved in the sexual transmission of HIV-1.     

GHB: a home brew

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.     

Effects of chronic arterial hypertension on constitutive and induced intercellular adhesion molecule-1 expression in vivo

Recent reports indicate that bacterial endotoxin (lipopolysaccharide) and cytokines elicit a more profound increase in the surface expression of intercellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells derived from spontaneously hypertensive (SHR) versus normotensive Wistar-Kyoto rats (WKY). Our objective in this study was to characterize and compare in vivo ICAM-1 expression in SHR and WKY under basal conditions and after 5 hours of endothelial cell activation with either lipopolysaccharide (5 mg/kg i.p.) or tumor necrosis factor-alpha (TNF-alpha; 1, 5, and 10 micrograms/kg i.p.). ICAM-1 expression was quantified in different tissues by the double-radiolabeled monoclonal antibody technique. When constitutive (baseline) ICAM-1 expression was corrected for endothelial cell surface area, significantly higher values were noted in SHR than WKY but only in splanchnic organs. Lipopolysaccharide and TNF-alpha elicited significant increases in ICAM-1 expression in all tissues of both WKY and SHR. However, the magnitude of the lipopolysaccharide-induced ICAM-1 upregulation in heart, stomach, skeletal muscle, and brain was significantly lower in SHR than WKY. A similar blunted ICAM-1 upregulation was noted in the stomach of SHR after administration of 5 micrograms/kg TNF-alpha. The differences in induced ICAM-1 expression between SHR and WKY do not appear to be due to differences in endothelial cell surface area or plasma glucocorticoid levels. These results suggest that chronic arterial hypertension results in altered ICAM-1 expression on the endothelium, which may contribute to the abnormal inflammatory responses associated with this disease.     

Factor V Leiden is not common in children with portal vein thrombosis

Portal vein thrombosis (PVT) is a rare condition affecting both children and adults, and occurs in association with a wide variety of clinical situations. On the other hand, the development of PVT in patients under these situations indicates that other contributing factors could be involved. Recently a missense mutation in the factor V gene (1691G-->A), known as factor V Leiden, has been identified and results in abnormal factor V product, resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis. This study was carried out to verify if children with PVT have an increase in frequency of factor V Leiden. Allele-specific restriction analysis and single strand conformational polymorphism (SSCP) were used to test for factor V Leiden in 20 children with PVT and 64 normal children. None of the PVT children were heterozygous or homozygous for the factor V Leiden, and one control child was heterozygous. This study demonstrates that factor V Leiden is not common in children with PVT, and is not a prerequisite for this thrombotic event.