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Biomedical subjects

C F Yen

Publications and source records attributed to C F Yen.

47 records · Page 3Linked to original sources

Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats.

The study was designed to compare the therapeutic efficacy of estrogen, the bisphosphonate risedronate (NE-58095), and PTH for restoration of lost bone mass in osteopenic, ovariectomized (OVX) rats. In addition, the skeletal effects of these single treatments were compared to those of concurrent treatments with PTH + estrogen or PTH + NE-58095. OVX rats were untreated for the first 4 weeks postovariectomy to allow for the development of moderate tibial osteopenia. These animals were then subjected to the various treatments for periods of 5, 10, and 15 weeks. Their proximal tibiae were processed undecalcified for quantitative bone histomorphometry. Treatment of osteopenic OVX rats with estrogen or NE-58095 alone depressed bone turnover and prevented additional cancellous bone loss from occurring during the treatment period. However, these therapeutic agents failed to restore lost bone in OVX rats to control levels. In contrast, OVX rats treated with PTH alone exhibited a marked stimulation of bone formation which resulted in augmentation of cancellous bone mass to a level 2-fold greater than that of vehicle-treated control rats. Concurrent treatment of OVX rats with PTH + estrogen as well as PTH + NE-58095 also effectively reversed cancellous osteopenia in OVX rats, but did not appear to be more beneficial to the estrogen-deplete skeleton than treatment with PTH alone. The results indicate that PTH is a powerful stimulator of bone formation and completely restores lost cancellous bone in osteopenic OVX rats. Furthermore, the bone anabolic effects of PTH are much more pronounced than those of estrogen or bisphosphonates. These findings in an animal model of estrogen depletion provide support for PTH as a potentially effective treatment for oophorectomized and postmenopausal women with established osteoporosis.

Animals↗

Insulin increases intracellular magnesium transport in human platelets.

Evidence suggests that magnesium (Mg) deficiency may play a key role in cardiovascular disease. In particular, Mg deficiency may lead to a potentiation of platelet aggregation. However, the factor(s) regulating intracellular-free Mg concentration ([Mg2+]i) in platelets is not known. We studied the effects of insulin on the changes of [Mg2+]i in human platelets. Preincubation of hirudinized platelet-rich plasma with insulin had a dose- and time-dependent effect on the increase of [Mg2+]i measured in Mag-fura-2-loaded cells with a fluorescence spectrophotometer. The maximal effect was achieved by incubation with 200 microU/mL insulin for 30 min. [Mg2+]i increased from the basal value of 266 +/- 23 mumol to 355 +/- 46 (SD, P < 0.001). In the presence of an antiinsulin receptor monoclonal antibody the effect of insulin was abolished suggesting that the Mg transport mechanism was an insulin-receptor mediated process. Furthermore, the insulin-stimulated Mg transport was inhibited by the addition of chelating agent ethylenediaminete-traacetate while the receptor binding was not altered. These findings suggest that insulin can translocate Mg from the extracellular space. Insulin alone had no effect on the changes of intracellular calcium (Ca) concentration using Ca-Fura-2 as a probe. In addition, glucose (5 mg/mL) was not effective in altering either the Mg or Ca concentration. Insulin (100 microU/mL) decreased thrombin-induced platelet aggregation (washed platelets resuspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Tyrode buffer). Similarly, the production of the proaggregatory eicosanoids thromboxane B2 was inhibited by insulin from 16 +/- 1 ng/10(8) platelets to 13 +/- 2 (P < 0.05). The results suggest that insulin, through the interactions with its receptors may be a key factor regulating, Mg transport in human platelets.

Biological Transport↗

Release of different fractions of epidermal growth factor from human platelets in vitro: preferential release of 140 kDa fraction.

Platelet-rich plasma in acidic-citrate-dextrose anticoagulant was kept for 5 days in an oxygen-permeable bag at 22 degrees C in an incubator/rotator. Platelet count remained stable throughout the experiment. On days 0, 3 and 5, aliquots were removed; platelets were isolated by centrifugation at 22 degrees C, 1500 g for 20 min, reconstituted to the original volume with PBS buffer, and the contents of alpha-granules were released by repeated freezing and thawing. Epidermal growth factor (EGF) and beta-thromboglobulin (beta-TG) in the platelet-poor plasma and platelet lysates were determined by radioimmunoassays. Results indicated that in platelet-free plasma, both total EGF and beta-TG increased 3-5-fold after 5 days; this amount represented 10-20% of the factors stored in the platelets. Correspondingly, the EGF and beta-TG contents of the platelet lysates exhibited accompanying decreases. HPLC fractionation showed that the main EGF fraction which progressively decreased in the lysates and increased in plasma had a molecular mass of 140 kDa. The contents of the 67 kDa and 6 kDa fractions did not change substantially. We conclude that under these conditions, the 140 kDa fraction was released preferentially. In view of these and previous experiments, it seems likely that different organs contribute to plasma EGF fractions.

Adolescent↗

Effect of extracellular magnesium on platelet activation and intracellular calcium mobilization.

A dose-dependent effect of magnesium on the inhibition of platelet aggregation and release of ATP from dense granules was observed in human platelets (in whole blood, platelet-rich plasma, or washed platelets) against various aggregation agents (ADP, U46619, collagen, or thrombin). The synthesis and release of the proaggregatory cyclooxygenase (CO) and lipoxygenase (LO) products, thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively, in platelets were also inhibited by Mg in a dose-dependent manner (IC50 4 to 6 mmol/L). These Mg-mediated activities were further enhanced when platelets were preincubated with insulin (100 microU/mL). The effect of extracellular Mg on the change of intracellular calcium concentration ([Ca2+]i) was assessed using Fura-2/AM loaded cells in the presence or absence of extracellular Ca. Thrombin-stimulated influx of Ca ions decreased from 194 +/- 30 nmol/L to 156 +/- 21 nmol/L in the presence of 5 mmol/L Mg and to 111 +/- 16 nmol/L in 10 mmol/L Mg. However, the intracellular Ca release (as determined in the presence of 5 mmol/L EGTA) was not affected by Mg. The intracellular Ca-dependent protein kinase C and myosin light chain kinase activities on the phosphorylation of endogenous p47 and p20 proteins studied after 2 min of thrombin addition decreased only 10 to 25% in the presence of 5 to 10 mmol/L Mg. Similar results were obtained when EGTA was added prior to the initiation of protein phosphorylation. We conclude that Mg can dose dependently inhibit a wide variety of agonists on platelet aggregation. Furthermore, insulin can potentiate the inhibitory effects of Mg on platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Histomorphometric studies of dermal bone in the desert tortoise, Gopherus agassizii.

Dermal bone biopsies were collected from the periphery of the carapaces of adult desert tortoises (Gopherus agassizii) from grazed and ungrazed habitats near the Arizona/Utah border (USA). Quantitative bone histomorphometry was performed on these biopsies as well as on dermal bone biopsies collected from captive juvenile desert tortoises. Except for mild osteomalacia, carapaces of adult desert tortoises from the grazed habitat were relatively normal. No signs of osteopenia were observed. Based on the low numbers of osteoblasts and osteoclasts in dermal bone of both populations of adult desert tortoises, it appears that the peripheral carapace is relatively inert with very low levels of dermal bone turnover. Bone cells and osteoid were more common in dermal bone biopsies from the carapace and plastron of captive juvenile desert tortoises than in adult desert tortoises. However, the great variability in the incidence of bone cells among individuals and the difficulty in collecting juvenile desert tortoises in the field limit the usefulness of dermal bone biopsies from animals of this age group. Based on these results, we propose that dermal bone of the peripheral carapace is a poor sample site for evaluating the effects of dietary or environmental conditions on calcified tissues in desert tortoises.

Animals↗

Estrogen and diphosphonate treatment provide long-term protection against osteopenia in ovariectomized rats.

The goal of this study is to determine whether the previously observed, short-term protective effect of estrogen and diphosphonate compounds against osteopenia in ovariectomized (OVX) rats can be maintained for an entire year. Sham-operated control and OVX rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and risedronate (NE-58095) for 360 days after surgery. Their proximal tibiae and first lumbar vertebrae were processed undecalcified for quantitative bone histomorphometry. Both skeletal sites in vehicle-treated OVX rats were characterized by decreased cancellous bone volume and increases in most cellular and fluorochrome-based indices of bone formation and resorption. Treatment of OVX rats with estrogen or diphosphonate compounds depressed bone turnover and provided nearly complete protection against cancellous bone loss. Long-term EHDP treatment induced a moderate mineralization defect, as indicated by increased absolute osteoid volume and a high proportion of osteoid surfaces devoid of adjacent osteoblasts. In contrast, NE-58095 had minimal effects on bone mineralization. These findings indicate that diphosphonate compounds and estrogen provide long-term protection against tibial and vertebral osteopenia in OVX rats. They further indicate that diphosphonate compounds merit consideration as an alternative to estrogen for the prevention of postmenopausal bone loss.

Animals↗

Skeletal effects of calcitonin in ovariectomized rats.

Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.

Animals↗

Anabolic effects of parathyroid hormone on cortical bone in ovariectomized rats.

The purpose of this study was to determine whether PTH has anabolic effects on cortical bone in ovariectomized (OVX) rats similar to those previously observed in cancellous bone. Groups of OVX rats were untreated for the first 4 weeks postovariectomy followed by treatment for 5-, 10-, or 15-week periods with vehicle, estrogen, the bisphosphonate rise-dronate (NE-58095), PTH, PTH+estrogen or PTH+NE-58095. A group of sham-operated control rats was treated with vehicle alone. Cross sections of the tibial diaphysis immediately proximal to the tibiofibular junction were subjected to quantitative bone histomorphometry. In comparison to vehicle-treated control rats, the following structural changes were detected in cortical bone of OVX rats after 15 weeks of vehicle treatment: increased cortical bone tissue area, increased cortical bone area, and a trend for increased bone marrow area. Indices of periosteal bone formation were increased in vehicle-treated OVX rats at 5 weeks, but declined to control levels at the later time points. In addition, vehicle-treated OVX rats exhibited a nonsignificant trend for increased endocortical bone formation relative to vehicle-treated control rats throughout most of the study. Estrogen, but not NE-58095, prevented most of the changes in cortical bone structure associated with ovariectomy. In comparison to vehicle treatment of OVX rats, estrogen decreased both periosteal and endocortical bone formation whereas NE-58095 decreased endocortical, but not periosteal, bone formation. Treatment of OVX rats with PTH alone increased cortical bone area and width as well as decreased bone marrow area compared to vehicle-treated OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Water balance, growth, development, and survival of arboreal frog eggs (Chirixalus eiffingeri, Rhacophoridae): importance of egg distribution in bamboo stumps.

We studied the effects of substrate moisture and flooding on the arboreal eggs of Chirixalus eiffingeri and determined the possible causes of egg mortality. Eggs appear highly permeable to water vapor, losing 16.24% and 38.38% of initial egg mass in 2 h at 90% and 45% relative humidity, respectively. Eggs that experienced positive water uptake developed faster, hatched earlier with larger hatchlings, and had greater hatching success than eggs that experienced negligible or negative water uptake. The hatching success of eggs that were submerged in water in bamboo stumps was significantly lower than that of eggs that were incubated on the water surface and was significantly correlated with the water PO2. In some bamboo stumps, we observed chironomid and tipulid larvae preying on submerged eggs. A dilution of water collected from bamboo stumps did not increase the hatching success of eggs. The water PO2 of bamboo stumps in the field was 67.4+/-18.8 mmHg, and the degree of hypoxia of water in each bamboo stump was correlated with the turbidity. Our findings demonstrated that the vertical distribution of C. eiffingeri eggs on walls of bamboo stumps significantly influenced the growth, development, and survival of embryos. Eggs deposited too far from the water may become desiccated, while eggs deposited too close to the water may become submerged and die of hypoxia or predation by insect larvae.

Adaptation, Physiological↗

Comparison the efficacy of laparosonic coagulating shears and electrosurgery in laparoscopically assisted vaginal hysterectomy: preliminary results.

OBJECTIVE: To compare the safety and effectiveness of laparosonic coagulating shears (LCS) and electrosurgery for use in laparoscopically assisted vaginal hysterectomy (LAVH). STUDY DESIGN: In this prospective study, patients undergoing LAVH performed by one of the authors from October 1997 to January 1998 were assigned at random to the electrosurgery group (n = 20) or the LCS group (n = 20). Procedures performed with LCS or electrosurgery included coagulation and separation of infundibulopelvic or utero-ovarian round ligaments, vesico-uterine-visceral peritoneal fold dissection, and anterior and posterior colpotomy. Outcome measures were operative time, blood loss, decrease in hemoglobin values, and length of hospitalization. RESULTS: The mean operative time (90+/-22.9 min versus 80.3+/-17.1 min, P = 0.391), blood loss (308+/-167 ml versus 250+/-104 ml, P = 0.11), and hemoglobin decrease (1.57+/-0.769 mg/dl versus 1.36+/-0.886 mg/dl, P = 0.55) were slightly greater in the LCS group than in the electrosurgery group, although these differences were not statistically significant. The length of hospital stay was similar in the two groups (5 days). No patients developed serious complications related to electrosurgery or LCS. CONCLUSION: Our findings indicate that LCS is as safe and effective as electrosurgery, and may offer an alternative option for patients undergoing LAVH.

Blood Loss, Surgical↗

Extraperitoneoscopic colposuspension using CO2 distension method.

PURPOSE: To validate our experience in extraperitoneoscopic colposuspension for genuine stress incontinence. MATERIALS AND METHODS: Between March 1995 and July 1996, 48 women who had genuine stress incontinence underwent extraperitoneoscopic colposuspension in our institute. After standard laparascopic surgery preparation, a 10 mm puncture site was made midline just in the cm above the pubic hair line, and the extraperitoneal space was developed with the higher pressure of insufflating CO2. A pair of sutures was inserted at the level of the midurethral and unrethrovesical junction with Cooper's ligament. RESULTS: All of these patients underwent the same procedures. The average blood loss was less than 50 ml, with a range from 10 to 200 ml. The operative time was from 20 to 90 min, with a mean time of 32 min. There was one bladder injury, 2 cases of voiding difficulties and 2 of detrussor instability in our series and the overall complication rate was 10.4%. So far, 45 of the 48 patients are satisfied with the surgery. CONCLUSIONS: Laparoscopic Burch colposuspension is a practicable surgical procedure for managing stress incontinence. Extraperitoneal space was created easily with the higher pressure of insufflating CO2. An extraperitoneoscopic approach can reduce the necessity of laparscopic suturing. Moreover, it avoids violating the peritonel cavity and reduces the potential risk of postoperative adhesion formation and the discomfort resulting from pneumoperitonium. Thus, extraperitoneal colposuspension affords an alternative to laparoscopic or abdominal retropubic colposuspension in well-selected patients.

Adult↗