Changes in vascular basement membrane in the endometrium of Norplant users.
(9/1204)
Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature, and in particular an increase in vascular fragility, may contribute to this bleeding. In this study, endometrial vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant. Endometrial vascular density was increased from a mean (+/- SEM) of 189.6 +/- 7.0 vessels/mm2 during the control cycle to 253.9 +/- 80.7 vessels/mm2 at 2-13 weeks of Norplant exposure, and to 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks. During the control cycle, a mean of 161.4 +/- 4.5 vessels/mm2 stained for collagen IV (85% of all vessels), while at 2-13 weeks, 144.5 +/- 13.0 vessels/mm2 stained for collagen IV (57% of all vessels) (t ratio = 2.08, P = 0.0057). By 14-42 weeks, 71% of vessels (151.0 +/- 9.8) vessels/mm2 were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial vascular laminin was also reduced following Norplant insertion, from a mean of 176.0 +/- 4.2 vessels/mm2 in the control cycle (93% of vessels), to 156.3 +/- 6.7 vessels/mm2 at 2-13 weeks of exposure (57% of vessels) (t ratio = 2.08, P = 0.01). By 14-42 weeks of exposure to Norplant, 162.5 +/- 9 vessels/mm2 (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 +/- 3.0 vessels/mm2 during the control cycle (31% of vessels) to 43.6 +/- 5.6 vessels/mm2 (only 17% of vessels) at 2-13 weeks (t ratio = 2.08, P = 0.025). At 14-42 weeks, only 19% of vessels stained for HSPG (41.3 +/- 5.8 vessels/mm2; t ratio = 2.04, P = 0.009). (+info)
Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinase-9 (gelatinase B).
(10/1204)
Norplant, subdermally implanted slow-release levonorgestrel, is an effective and widely used contraceptive agent but has a high rate of discontinuation due to unacceptable abnormal uterine bleeding. Matrix metalloproteinases (MMPs) are expressed in normal cycling endometrium and are postulated to be responsible for the tissue breakdown at menstruation. We have compared the immunolocalization of MMP-9 and migratory cells in endometrium from Indonesian women using Norplant with normal controls. Positive MMP-9 immunostaining was observed intracellularly within stromal and intravascular leukocytes and extracellularly in areas of tissue lysis adjacent to these migratory cells. The MMP-9 positive cells were identified as neutrophils, eosinophils, CD3+ T-cells and macrophages. Quantitative assessment revealed that the number of MMP-9 positive cells, neutrophils and eosinophils were significantly increased in those endometrial biopsies from Norplant users displaying a shedding morphology and in normal controls at menstruation. There was no correlation between the number of MMP-9 positive cells and the number of bleeding days reported. Endometrial immunostaining for tissue inhibitor of metalloproteinases was similar in Norplant users and normal controls. These results suggest that MMP-9, an enzyme capable of degrading basement membrane components, may be involved in endometrial breakdown in women using Norplant. (+info)
Paracrine immunotherapy with interleukin-2 and local chemotherapy is synergistic in the treatment of experimental brain tumors.
(11/1204)
Potent immune responses against malignant brain tumors can be elicited by paracrine intracranial (i.c.) immunotherapy with interleukin (IL)-2. Additionally, i.c. delivery of carmustine via biodegradable polymers has been shown to significantly prolong survival in both animal models and clinical trials. In this study, we show that the combination of paracrine immunotherapy, with nonreplicating genetically engineered tumor cells that produce IL-2, and local delivery of chemotherapy by biodegradable polymers prolongs survival in a synergistic manner in mice challenged intracranially with a lethal murine brain tumor. Animals receiving IL-2-transduced cells and polymers containing 10% 1,3-bis(2-chloroethyl)-1-nitrosourea had significantly improved survival compared with animals receiving IL-2-transduced cells or 10% 1,3-bis(2-chloroethyl)-1-nitrosourea alone. Median survival for the control group was 19 days. Survival in animals receiving IL-2-transduced cells and 1% carboplatin-containing polymers was also significantly improved compared with either therapy alone. Histopathological examination on day 14 of animals receiving combination treatment showed rare degenerating tumor cells. In addition to tissue necrosis surrounding the polymer, a marked inflammatory reaction was observed. In long-term survivors (all animals receiving combination treatment), no tumor was observed and the inflammatory reaction was completely resolved. The brains of animals receiving combination therapy showed both tissue necrosis due to local chemotherapy and strong inflammation due to paracrine immunotherapy. The demonstration of synergy between paracrine IL-2 and local i.c. delivery of antineoplastic drugs is novel and may provide a combined treatment strategy for use against both primary and metastatic i.c. tumors. (+info)
Role of oestradiol in the regulation of the seasonal antler cycle in female reindeer, Rangifer tarandus.
(12/1204)
Reindeer (or caribou), Rangifer tarandus, is the only extant species of deer in which females as well as males normally develop antlers that are cast and regrown each year. This study investigated the role of ovarian oestradiol in the regulation of the seasonal antler cycle in female reindeer. Ovariectomized Norwegian reindeer living outdoors in northern Norway (69 degrees N) were treated with continuous-release subcutaneous Silastic implants containing oestradiol, which maintained the blood concentrations of oestradiol within the physiological range for the mating season from June to October-November. The treatment with oestradiol induced the synchronized maturation of the antlers and rapid cleaning of the velvet-like skin in August-September in the ovariectomized reindeer, a pattern very similar to that observed in ovary-intact controls living under the same conditions. The removal of the steroid implant in October-November caused the premature casting of the antlers in early winter in two of five animals, while the remainder cast at the normal time in spring; this response was seen whether the animals had received one or two oestradiol implants in autumn. The antlers developed by the ovariectomized, oestradiol-treated females were significantly heavier and carried more branches than the ovariectomized animals without oestradiol replacement, and were marginally heavier than the antlers of intact controls. These results support the view that oestradiol is the biologically active steroid secreted by the ovary in intact female reindeers that induces the normal development of the antlers. Oestradiol stimulates the growth and mineralization of the antler bone, the cleaning of the velvet, and suppresses the casting of the hard antlers. This endocrine control ensures that the hard antlers, which function as weapons, are retained throughout the autumn and winter when the females are normally pregnant and when competition between females over food in the snow is most intense; hence there is a reproductive advantage to explain the evolution of antlers in females. (+info)
Partial blocking of NMDA receptors reduces plastic changes induced by short-lasting classical conditioning in the SI barrel cortex of adult mice.
(13/1204)
The effect of blockade of N-methyl-D-aspartate (NMDA) receptors in the barrel cortex upon the learning-induced changes of the cortical body map was examined in adult mice. We have previously found that three sensory conditioning sessions, in which stimulation of a row of vibrissae was paired with a tail shock, produced an enlargement of the functional representation of a row of vibrissae stimulated during training. Implantation of the slow release polymer Elvax, containing 2-amino-5-phosphonovalerate (APV, 50 mM), in the vicinity of the barrel cortex was performed 1 day before conditioning to block NMDA receptors. The cortical representation of a trained row of vibrissae was visualized with 2-deoxyglucose (2DG) functional brain mapping 1 day after the completion of the conditioning procedure. The partial blockade of NMDA receptors within the barrel cortex reduced (by half) the expansion of the cortical representation of a trained row of vibrissae as compared to the enlargement of the cortical representation of a trained row found in untreated (60%) and Elvax-PBS implanted (47%) mice. The results provide evidence that the learning-induced processes of cortical map reorganization involve mechanisms that depend on NMDA receptor activation. (+info)
Effects of sustained phencyclidine exposure on sensorimotor gating of startle in rats.
(14/1204)
Phencyclidine (PCP), a non-competitive NMDA antagonist with actions at multiple other central nervous system receptors, can cause both acute and lasting psychoses in humans, and has also been used in cross-species models of psychosis. Acute exposure to PCP in rats produces behavioral changes, including a loss of prepulse inhibition (PPI) of the startle reflex, which parallels the loss of PPI observed in schizophrenia patients. Sustained exposure to PCP in rats produces neuropathological changes in several limbic regions and prolonged behavioral abnormalities that may parallel neuropsychological deficits in schizophrenia. It is unclear whether sustained PCP exposure will also produce a loss of prepulse inhibition which parallels the decrease observed in schizophrenia patients. In the present study, we examined changes in PPI during and after sustained PCP administration, using 5-day PCP exposure via subcutaneous osmotic minipumps, or 14-day PCP exposure via repeated intraperitoneal injections. In both forms of drug delivery, PPI was disrupted during, but not after, sustained drug exposure. PPI does not appear to be sensitive to neuropathological effects of sustained PCP exposure. (+info)
Estrogen-inducible, sex-specific expression of brain-derived neurotrophic factor mRNA in a forebrain song control nucleus of the juvenile zebra finch.
(15/1204)
The expression of brain-derived neurotrophic factor (BDNF) mRNA is increased significantly within the high vocal center (HVc) of male but not female zebra finches from posthatching day 30-35 on. The population of HVc cells expressing BDNF mRNA included 35% of the neurons projecting to the nucleus robustus of the archistriatum (RA). In the RA and in RA-projecting neurons of the lateral portion of the magnocellular nucleus of the anterior neostriatum, BDNF mRNA was expressed at very low levels in both sexes. The BDNF-receptor trkB mRNA was expressed in the RA, in RA-projecting neurons of lateral portion of the magnocellular nucleus of the anterior neostriatum, and in the HVc, except in most of its RA-projecting neurons. Premature stimulation and an inhibitory effect on the normal increase of the BDNF mRNA expression in juvenile males occurred after treatments with 17beta-estradiol and the aromatase inhibitor fadrozole, respectively. The up-regulation of the BDNF expression in the HVc could be a mechanism by which estrogen triggers the differentiation of cells within and connected to the HVc of male zebra finches. (+info)
A Saprolegnia parasitica challenge system for rainbow trout: assessment of Pyceze as an anti-fungal agent for both fish and ova.
(16/1204)
A reproducible Saprolegnia parasitica spore delivery system was developed and demonstrated to be effective in providing a sustained spore challenge for up to 10 d. Treatment of rainbow trout with slow-release intraperitoneal implants containing cortisol resulted in chronically elevated blood cortisol levels and rendered the fish susceptible to infection by S. parasitica when exposed to the spore challenge. Sham-implanted fish were not susceptible to infection. Bronopol (2-bromo-2-nitro-propane-1,3-diol), formulated as Pyceze, was effective in protecting predisposed fish from infection by S. parasitica when administered as a daily bath/flush treatment at concentrations of 15 mg l-1 and greater. Pyceze was also demonstrated to protect fertilised rainbow trout ova from S. parasitica challenge when administered as a daily bath/flush treatment at concentrations of between 30 and 100 mg l-1. Pyceze appears to qualify as a safe and effective replacement for malachite green and formalin in the prevention of fungal infections in the aquaculture environment. (+info)