Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.
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PMID:The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts. 158 9

Systemic sodium fluoride has been used in the treatment of osteoporosis. Recent studies have shown that it has a positive risk/benefit ratio for use in increasing spinal trabecular bone density. However, thinning of the cortices of the long bones with a resulting increase in fracture incidence has been observed. This study was designed to determine the response of bone to sodium fluoride released from a biodegradable polymer matrix, a technique which could potentially deliver it locally to a site of need in the skeleton which has a positive response to fluoride. In one group of mature New Zealand white rabbits, cylindrical poly(D,L-lactic acid) (PLA) implants, with or without impregnated sodium fluoride, were implanted into the contralateral femoral trochanters and tibial metaphyses. In a second group, similar implants were placed in adjacent vertebrae. Four weeks postimplantation, the femora, tibiae, and vertebrae were removed, sectioned, cleaned of all but mineralized tissue, and the surfaces of the sections stained. The stained surfaces were imaged and analyzed for morphometric properties of the trabeculae. Comparing contralateral vertebrae, those exposed to sodium fluoride had significantly thickened trabeculae, with decreased spacing between them and a greater bone fraction. A similar increase in trabecular width was found in the subchondral bone of the proximal tibiae exposed to local release fluoride. Femoral sections showed no difference, possibly due to the lack of extensive trabecular bone in the region chosen for study.
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PMID:Effect of controlled local release of sodium fluoride on trabecular bone. 161 33

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.
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PMID:The response of the fetal kidney to obstruction. 164 May 11

We have studied the pathological changes of the ciliary body in Royal College of Surgeons (RCS) rats with an inherited retinal degeneration. Morphometric analyses were performed on sectioned ciliary bodies by a computerized morphometry system. Age-matched non-pigmented Sprague-Dawley (SD) rats were used as the control animals. The ciliary body of 26-day-old RCS dystrophic rats showed normal structure. However, the length and height of the pars plicata of the ciliary body became shorter and the area became smaller with increased age. Significant decreases in the values of these three parameters were observed between 26-day-old and 3-month-old RCS dystrophic rats. These parameters also showed significant differences when values of 3-month-old RCS dystrophic rats were compared to those of 3-month-old control SD rats. The same trends were observed in the ciliary body measurements in RCS dystrophic rats up to 1 year of age. Scanning electron microscopic examination demonstrated the progressive thinning of the pars plicata of the ciliary body with age in the RCS dystrophic rats. The total volume of the ciliary process of 6-month-old RCS dystrophic rats appeared to be one-half that of 26-day-old RCS dystrophic rats. Transmission electron microscopy revealed progressive cellular degenerative changes in the non-pigmented and pigmented ciliary epithelium of the RCS dystrophic rats. It was apparent that the pigmented ciliary epithelium had more severe degenerative changes than the non-pigmented ciliary epithelium. Immunostaining for Na+ + K+ ATPase of the ciliary epithelium was found to be less in the RCS dystrophic rats than in age-matched controls. This result suggests a possible dysfunction of ion transport in the ciliary body of the RCS dystrophic rats, which may account for their increased incidence of cataract formation. Although the mechanisms for the ciliary body degeneration in RCS dystrophic rats remain speculative, these findings add a new area of interest in this model of inherited retinal dystrophy.
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PMID:Ciliary body degeneration in the Royal College of Surgeons dystrophic rat. 164 4

Fetuses of streptozotocin-induced diabetic rats exhibited delayed lung maturation and a 40% reduction in the steady-state level of lung Na+,K(+)-ATPase alpha 1 subunit mRNA and Na+,K(+)-ATPase activity at 21 d of gestation. In in situ hybridization experiments the signal specific for Na(+)-pump alpha 1 subunit message was strongest above columnar epithelial cells of air-conducting structures. Strong labeling was also present above cuboidal cells lining the forming alveoli, but not above mesenchymal cells. Immunocytochemical localization of the protein paralleled the distribution of the mRNA. Mesenchymal cells were more abundant in fetal lungs of diabetic mothers, and thus the decreased overall levels of Na+,K(+)-ATPase may result from the observed morphological pulmonary immaturity. One day after birth there was no apparent difference in lung morphology at the light microscopic level, in the localization or the steady-state level of Na+,K(+)-ATPase alpha 1 isoform mRNA, or in enzyme activity. Na+,K(+)-ATPase has a likely role in the active phase of fluid absorption in the airways of newborns before the onset of breathing. Decreased fluid clearance and lack of thinning of the lung's connective tissue may contribute to the increased risk for respiratory distress in infants of diabetic mothers.
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PMID:Effects of maternal diabetes on fetal rat lung ion transport. Contribution of alveolar and bronchiolar epithelial cells to Na+,K(+)-ATPase expression. 184 38

To study the effects of a single parenteral dose of indomethacin on gastric epithelial proliferation, we performed the following study. Male Wistar rats weighing about 200 g were divided into two groups and given single intraperitoneal injections of indomethacin 5 mg/kg, either suspended in 0.5% carboxymethyl cellulose sodium salt or vehicle alone, after an overnight fast. After 6 h, all rats were injected by tail vein with tritiated thymidine, 1 microCi/g body weight, to label proliferating cells and were killed 1 h later. Sections from fundic and antral mucosae were processed for light autoradiography. Parenteral indomethacin resulted in spotty erosions in fundic mucosa. Histologically, there was congestion with or without epithelial disruption. These areas were excluded in the proliferation measurements. There was a significant decrease not only in the number of labeled cells but also in the thickness of the proliferative zone with the thinning of the entire mucosal thickness in the fundic mucosa. None of the measurements in antral mucosa showed significant difference. These results showed that a single parenteral injection of indomethacin inhibits epithelial proliferation and decreases mucosal thickness in fundic, but not antral mucosa of the rat.
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PMID:Effects of single parenteral indomethacin injection in rat fundic and antral epithelial proliferation. 221 52

Spontaneous fractures were reported to be rare (less than 1%) in 1664 hospital admissions for hip fracture in the 1950s in Sweden. We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks, all subcapital initially. In 7 patients who continued treatment there were later femoral neck or shaft fractures; in 6, these were bilateral (one followed a fall). In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery. Five were incomplete (stress) fractures. All were treated with supplementary calcium 1 g daily; 10 had vitamin D supplementation. In all patients where the timing was known, the initial and subsequent fractures were preceded by, or associated with increased bone turnover as measured by plasma alkaline phosphatase (pAlP) (i.e., they were all "good responders"). Two had pretreatment hip fractures following falls. We compared these 11 (Group 1) and another identically treated group of 14 patients (Group 2), without spontaneous femoral fractures and not different in mean age, pretreatment vertebral fractures, years since menopause, fluoride dosage, and plasma creatinine. Group 1 had a lower (p less than 0.05) index of cortical bone in the femoral neck, as assessed by the ratio "calcar width/femoral neck minimum width." The 6 biopsied fluorotic patients from Group 1 had a higher (p less than 0.05) bone fluoride content than the 4 biopsied fluorotic patients from Group 2. Furthermore, histological cortical features of thinning, increased porosity, and advanced tunneling resorption characterized Group 1 posttreatment biopsies. There were no significant differences in peak pAlP responses in the two groups. Mild asymptomatic vitamin D excess may have been a contributing factor in three Group 1 patients. Two further treatment groups have been studied more recently by forearm single-photon absorptiometry (SPA) at two sites; a cyclic NaF group (Group 3) and a calcium +/- vitamin D group (Group 4). Neither showed significant changes in forearm cortical bone density on treatment for 2 and 1.5 years, respectively, but Group 3 showed a significant increase in density at an ultradistal (60% trabecular) site. The pAlP response in Group 3 was significantly less than in Group 1. Spontaneous femoral neck or shaft fractures did not occur in either Groups 3 or 4. Therefore, we recommend: (1) Avoidance of sodium fluoride (NaF) treatment if pretreatment femoral fracture or thin femoral neck cortices exist.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Spontaneous hip fractures in fluoride-treated patients: potential causative factors. 233 31

Intracoronary administration of anticardiac cytotoxic serum increased the sarcolemma passive permeability for Ca2+ ions and reduced the activity of Na+-Ca2+ and Na+,K+-ATPase exchange in dogs. Electronic microscopy revealed thinning of glycocalix, destabilizing of the sarcolemma phospholipid bilayer, and development of intracellular oedema. Disturbances of the sarcolemma structure and function seem to be able to cause the development of cardiac insufficiency of immune origin.
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PMID:[Disordered ion-transport processes in the cardiomyocyte membranes in the immune action on the heart]. 245 77

The corneas of 50 normal subjects were examined before and after electroretinography performed with gold foil electrodes. Examination included slit-lamp biomicroscopy and staining with sodium fluorescein. All corneas were normal on examination prior to electroretinography. Three types of transient corneal changes were observed--punctate epithelial keratitis, corneal erosions, and stromal thinning. Each cornea was assigned a numerical damage score based on a simple scoring system. Thirty one subjects (62%) had some degree of corneal change, and in three cases (6%) follow-up was required. Multiple regression analysis was performed to discover any risk factors. Both age of the subject and the use of local anaesthetic were strongly associated with corneal changes.
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PMID:Transient corneal changes associated with the use of gold foil electrodes. 261 Nov 95

The influence of soft contact lenses (SCL) with low (37%, L) and high (65%, H) water content on rabbit corneas was investigated. The lenses were worn continuously for 1, 2, 4, 7, 10, 14, 21 or 28 days. The changes in corneal transparency, hydration and enzyme activities were studied. A slight change in corneal transparency due to higher hydration caused by a decreased activity of Na+-K+-dependent adenosine triphosphatase (Na+-K+-ATPase) in the corneal endothelium is followed by a decrease in the activity of gamma-glutamyl transferase (GGT). Slight morphological disturbances appear within 4 days in animals wearing SCL (L). SCL (H) produce similar changes one week later. Subsequently, the corneal epithelium becomes thinner and changes in the size of corneal endothelial cells are obvious. Disturbances of enzyme activities in cells of all corneal layers are present. In the epithelium highly increased activities of acid glycosidases, acid phosphatase, and dipeptidyl peptidase I and II, in keratocytes decreased activities of alkaline phosphatase and GGT, and in the endothelium decreased activity of Na+-K+-ATPase and GGT were found. These changes are more severe after SCL (L). In this case, inflammatory cells displaying high activities of lysosomal hydrolases appear in the anterior part of the stroma during the 3rd and 4th weeks and local degradation of glycosaminoglycans and proteins takes place. In contrast, after SCL (H) a remarkable thinning of the corneas was observed during extended wear, accompanied by decreased stainability of stromal glycosaminoglycans and highly decreased enzyme activities in keratocytes. The histochemical methods proved very useful in the assessment of lesions caused by a continuous wear of SCL.
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PMID:Disturbances in the rabbit cornea after short-term and long-term wear of hydrogel contact lenses. Usefulness of histochemical methods. 289 48


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