Sex differences in the effects of prenatal stress on stress-induced analgesia

Prenatal stress (PS) is known to cause demasculinizing and feminizing effects on sexually dimorphic behavior in laboratory animals. In three separate experiments performed on the same subjects at 10 week intervals, nociceptive sensitivity and the analgesic response to a cold-water swim stress were assessed in adult male and female Swiss-Webster mice that were either stressed prenatally or nonstressed (NS) control subjects. Experiment 1 showed analgesic magnitude to increase in female mice as a result of PS compared to nonstressed controls, whereas no changes were noted in male subjects. The increase in analgesia in female mice is maintained by estrogen. as gonadectomy eliminated the increase in Experiment 2, and estrogen replacement restored it in Experiment 3. Withdrawal latency to a noxious heat stimulus (hot-plate test) was also influenced by the PS manipulation; a decrease in hot-plate latency (indicating greater nociceptive sensitivity) was noted in PS subjects of both sexes in Experiment 1. Repeated testing (and/or age) may influence the effect of PS on nociceptive responses in a sex-dependent manner. The reduction in hot-plate latency was only present in males in Experiment 2, and was not present in either sex by Experiment 3. Thus, PS influences both baseline pain sensitivity and stress-induced analgesia responses in a sex and hormone-dependent fashion.     

Surgical management of subfoveal neovascularization in children.

OBJECTIVE: To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. INTERVENTION: Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. MAIN OUTCOME MEASURES: Visual acuity and recurrence of choroidal neovascular membrane. RESULTS: Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7-62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. CONCLUSION: Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.     

Effect of dietary inducer dimethylfumarate on glutathione in cultured human retinal pigment epithelial cells.

PURPOSE: To determine the effect of dimethylfumarate (DMF), an inducer of glutathione (GSH)-dependent detoxification, on intracellular GSH levels in cultured human retinal pigment epithelium (hRPE) cells, its mechanism of action, and its effect on hRPE cells subjected to oxidative injury. METHODS: Established hRPE cell lines were treated with DMF and assayed by high-pressure liquid chromatography for intracellular and extracellular GSH levels. Quantification of gamma-glutamylcysteine synthetase (GLCL) was determined through northern and western blot analyses, and activity was measured. Effects of pretreatment with DMF on GSH redox status of hRPE cells was determined. Sensitivity of hRPE cells to oxidative stress was determined using tert-butylhydroperoxide as the oxidative agent. RESULTS: Dimethylfumarate caused a transient decrease followed by a significant increase in intracellular GSH. Glutathione increased maximally at 24 hours with 100 to 200 microM DMF. The initial decrease could be accounted for by the formation of a DMF-GSH conjugate. Dimethylfumarate treatment increased the steady state mRNA expression of the regulatory subunit of GLCL, but no increase was seen for the catalytic subunit. However, protein levels were increased for both, and the catalytic activity of GLCL was also increased. Whereas the initial decrease in GSH made hRPE cells more susceptible to oxidative damage, pretreatment with DMF under conditions that increased intracellular GSH protected hRPE cells against oxidative damage. CONCLUSIONS: These results suggest a means by which the antioxidant capability of hRPE may be augmented without direct antioxidant supplementation. Specifically, a dietary compound that conjugates with GSH can induce GSH synthesis, increase GSH concentration, and improve protection by GSH-dependent detoxification pathways in hRPE. However, the early depletion of GSH before stimulated synthesis necessitates caution in prevention strategies using dietary inducers.     

Repeat Chlamydia trachomatis infection in women: analysis through a surveillance case registry in Washington State, 1993-1998

Repeat infections with Chlamydia trachomatis are associated with increased risk for long-term sequelae. The authors analyzed the frequency and predictors of repeat chlamydial infection by using a population-based chlamydia registry in Washington State and evaluated whether women would seek care at the same clinic for repeat infections. Among 32,698 women with an appropriately treated initial chlamydial infection during 1993-1998, 15% developed one or more repeat infections during a mean follow-up time of 3.4 years. Among women less than age 20 years at the time of initial infection, 6% were reinfected by 6 months, 11% by 1 year, and 17% by 2 years. Young age was the strongest predictor for one and two or more repeat infections after controlling for the length of follow-up and other variables. Only 36% of the repeat infections were diagnosed at the same clinical setting as the initial infection, and 50% were diagnosed at the same type of clinic. Adolescent girls had the least consistency in the source of care for chlamydia. This study suggests that efforts to prevent repeat chlamydial infection in young women remain an urgent public health priority and that the burden of repeat infection may be substantially higher than estimates from clinic-based studies.     

Photocoagulation to prevent retinal detachment in acute retinal necrosis

Retinal detachment (RD) occurs in more than 50% of eyes with acute retinal necrosis (ARN) and is the leading cause of visual loss in this syndrome. In order to decrease the incidence of RD in ARN, the authors treated 12 eyes of 10 patients with prophylactic laser photocoagulation. Retinal detachment occurred in two eyes (17%). Over the same time period, seven eyes with ARN did not receive prophylactic laser treatment, most often because of dense vitreous debris, with a 67% rate of RD. Prophylactic photocoagulation treatment should be considered in the management of patients with ARN.     

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples of a female- or hermaphrodite-specific sex attractant have been identified to date. In this study, we investigated the pheromone system of the gonochoristic sour paste nematode Panagrellus redivivus, which produces sex-specific attractants of the opposite sex. Activity-guided fractionation of the P. redivivus exometabolome revealed that males are strongly attracted to ascr#1 (also known as daumone), an ascaroside previously identified from Caenorhabditis elegans hermaphrodites. Female P. redivivus are repelled by high concentrations of ascr#1 but are specifically attracted to a previously unknown ascaroside that we named dhas#18, a dihydroxy derivative of the known ascr#18 and an ascaroside that features extensive functionalization of the lipid-derived side chain. Targeted profiling of the P. redivivus exometabolome revealed several additional ascarosides that did not induce strong chemotaxis. We show that P. redivivus females, but not males, produce the male-attracting ascr#1, whereas males, but not females, produce the female-attracting dhas#18. These results show that ascaroside biosynthesis in P. redivivus is highly sex-specific. Furthermore, the extensive side chain functionalization in dhas#18, which is reminiscent of polyketide-derived natural products, indicates unanticipated biosynthetic capabilities in nematodes.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Interrelationship between mitosis and endomitosis in cultures of human megakaryocyte progenitor cells [published erratum appears in Blood 1987 May;69(5):1547]

Sera from dogs rendered aplastic by total-body irradiation stimulate human bone marrow megakaryocyte progenitors to form megakaryocyte colonies in plasma clot cultures. In this investigation, we evaluated the effects of varying concentrations of such sera on both the mitotic and endomitotic phases of human megakaryocyte development in vitro. When low concentrations of aplastic canine sera (2.5% to 5.0% [vol/vol]) were added to cultures of human peripheral blood mononuclear cells in place of normal AB serum, megakaryocyte colony formation was augmented fivefold, cell numbers per colony increased approximately 2.5- fold, and the geometric mean megakaryocyte ploidy almost doubled. Further increasing the aplastic canine serum concentration from 10% to 30% (vol/vol) stimulated no additional colony formation. However, there was a further augmentation of cell numbers per colony associated with a progressive decrease in the mean megakaryocyte ploidy. Megakaryocyte cultures were harvested after 7, 12, 15, and 19 days of incubation, and these demonstrated that the lower mean ploidy values found at the higher concentrations of aplastic canine serum did not result from delayed endoreduplication. At all aplastic serum concentrations evaluated, there existed a strong correlation between nuclear ploidy and cell diameter. We conclude that both the mitotic and endomitotic events in human megakaryocytopoiesis may be influenced by a factor or factors present in aplastic canine serum. At lower in vitro concentrations, such sera stimulate both mitosis and endomitosis, which promotes the development of megakaryocyte colonies composed of larger cells with a higher mean ploidy. With increasing aplastic serum concentrations, colony formation plateaus and mitosis is favored over endomitosis. This results in colonies composed of more numerous but smaller megakaryocytes with a lower mean ploidy. Our data suggest that the size and extent of polyploidization that can be achieved by a developing megakaryocyte may be influenced by the mitotic prior history of its immediate precursor cell.