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G S Dizerega

Publications and source records attributed to G S Dizerega.

14 recordsLinked to original sources
PubMed1990

Temporal response of leukocyte accumulation in the thoracic cavity after two types of surgical injury.

To characterize pleural healing, we quantitated leukocyte accumulation in the pleural cavity and histological changes after two types of thoracic surgery. Rabbits underwent intercostal thoracotomy followed by abrasion of the parietal pleura and ligation and resection of the right middle lobe of the lung (group A), or only abrasion of the parietal pleura (group B). After surgery, the influx of leukocytes into the pleural exudate was characterized by an increase in the number of polymorphonuclear neutrophils (PMNs) followed by monocytes/macrophages. In group A, the total number of leukocytes reached maximum levels on days 5-7 after surgery, 80% of which were monocytes/macrophages. In group B, the total number of leukocytes reached peak levels on postsurgical day 3, 85% of which were monocytes/macrophages. Histologically, we observed a relative delay in pleural healing in group A compared with group B. An inflammatory response including appearance of fibrinous exudates and infiltration of acute inflammatory cells occurred in group A on days 1-3 after surgery. On days 5-7, an increase in submesothelial connective tissue was seen. An increase in cellularity was observed in this layer (fibroplasia) and the wound surface was covered by macrophagelike cells. In group B, disappearance of fibrinous exudates and fibroplasia occurred by day 3. In both groups, these histological changes from inflammatory phase to proliferative phase occurred on the day when the number of monocytes/macrophages in the pleural cavity reached peak levels. These data demonstrate that different types of thoracic injury alter the kinetics of leukocyte accumulation in the pleural cavity and the healing process of parietal pleura, suggesting that macrophages that accumulate in the pleural cavity may be implicated in postsurgical repair.

Animals↗
PubMed1989

Mitogenic and protein synthetic activity of tissue repair cells: control by the postsurgical macrophage.

It is well known that fibroblasts are a main source of extracellular matrix synthesis necessary for tissue repair. In addition, macrophages secrete products that are known to modulate synthesis of extracellular matrix. Accordingly, we studied the incorporation of [3H]thymidine, [3H]proline, and [35S]sulfate into macromolecules produced by fibroblasts recovered from the site of peritoneal tissue repair cultured with and without spent media from postsurgical peritoneal macrophages. Rabbits underwent resection and reanastomosis of their small intestines. Peritoneal exudative cells (PEC) were then collected on postsurgical day 5 and day 10 as well as from nonsurgical controls, separated by discontinuous Percoll gradient centrifugation, and cultured for 48 h. A second group of rabbits underwent peritoneal wall abrasion from which fibroblast tissue repair cells (TRC) were collected from the site of injury at postsurgical day 7 and maintained in culture for varying times. Incorporation of radiolabeled precursors into DNA, collagen, and sulfated proteoglycans was determined. Incorporation of [3H]thymidine and [3H]proline into untreated TRC gradually decreased with culture duration. Conversely, [35S]sulfate incorporation gradually increased during prolonged culture. Macrophage spent media increased the levels of [3H]thymidine incorporation by the TRC. [3H]Proline and [35S]sulfate incorporation into TRC were also stimulated by macrophage spent media. However, this stimulation may be due to the enhanced proliferation of TRC by macrophage spent media. In conclusion, tissue repair fibroblasts are activated for postsurgical repair at the site of injury by many factors including secretory products from postsurgical macrophages.

Animals↗
PubMed1986

Oocyte maturation inhibitor activity in human follicular fluid: quantitative determination in unstimulated and clomiphene citrate- and human menopausal gonadotropin-stimulated ovarian cycles.

Since removal of the oocyte from the intrafollicular milieu allows meiotic resumption and germinal vesical breakdown to proceed, the concept of an intrafollicular oocyte maturation inhibitor (OMI) has evolved. Accordingly, we asked the following questions: Is there OMI activity in human follicular fluid? Does OMI activity change with ovarian hyperstimulation? and Does OMI activity correlate with oocyte fertilization or the concentration of steroids in the corresponding follicular fluid? Fresh cumulus enclosed porcine oocytes from small follicles were incubated with human follicular fluid aspirates from normally menstruating patients with or without treatment: unstimulated follicles (N = 10), clomiphene citrate (150 mg/day) (N = 10)-treated cycles, and human menopausal gonadotropin (hMG) (N = 12)-treated cycles. A lyophylized porcine follicular fluid standard and serum-free culture media were used as positive and negative controls, respectively. After a 40-hr incubation with test materials, the oocytes were fixed, stained, and evaluated for oocyte maturation as determined by germinal vesical breakdown. Human follicular fluid, estradiol, progesterone, androstenedione, and testosterone levels were determined by radioimmunoassay. The 50% inhibitory dose (ID50) for OMI activity in follicular fluid from untreated, spontaneously menstruating women was less than that for follicular fluid from clomiphene-stimulated patients, which was less than that for follicular fluid from hMG-stimulated patients. The difference between OMI values from untreated and hMG-stimulated follicular fluids was statistically significant. Human oocytes removed from follicular fluid with higher OMI activity tended not to fertilize in vitro compared to the relatively lower OMI activity present in follicular fluid yielding oocytes which did fertilize.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Inhibition of canine spermatogonial mitosis with follicle regulatory protein.

Evidence was found that the Graafian follicle produces and secretes a hormone-like protein, referred to as follicle regulatory protein (FRP), which affects the responsivity of other follicles to gonadotropin stimulation. Since a similar material was identified in homogenates of bull testes, we evaluated the effects of FRP on the histology of seminiferous epithelium by its systemic injection into normal dogs. Mongrel dogs were injected IM with 5 mg of FRP for 17 consecutive days. The seminiferous epithelium was evaluated by light microscopy and divided into eight stages according to Foote. The relative frequency of stage 4 was significantly less in the FRP-treated than in the control group, but that of stage 7 was significantly greater in the FRP-treated group. The ratios of type B/type A spermatogonia for control and FRP-treated groups for stages 6-8 were 1.5, 5.8, 2.4, and 1.6, 4.3, 1.6, respectively. The tubular diameters of stages 6 and 7 were significantly different between the two groups. The numbers of tubules containing spermatogonial divisions were significantly decreased at stages 2 + 3 and stages 6 + 7 in the FRP-treated group. A clear decrease in the number of tubule profiles with spermatogonial divisions was present at stages 6 and 7 in the FRP-treated testis. Taken together, these findings suggest that FRP inhibits spermatogonial transformation of type A into type B.

Animals↗
PubMed1985

Modulation of leukotaxis by ibuprofen. A quantitative determination in vivo.

The purpose of this study was to evaluate the rabbit anterior eye chamber as a quantitative measure of leukotaxis using 51Cr-labeled homologous leukocytes and then to determine the effects of ibuprofen on N-formyl-methionyl-leucyl-phenylalanine (FMLP) -induced leukotaxis. Leukocyte accumulation was assessed at various intervals (0-24 h) after instillation of FMLP (10(-4) M, 40 microliters) and at various doses (FMLP 10(-6)-10(-4) M). New Zealand white rabbits (2.6-3.0 kg) were treated with ibuprofen for three days with the following regimens: 8.0, 17.5, 35.0, 70.0 mg/kg/ day. Leukocyte quantitation was determined using a direct cell count and recovery of 51Cr-labeled leukocytes from anterior eye chamber aspirations 3 h after their injection into the systemic circulation. FMLP induced a dose-dependent accumulation of leukocytes. Leukocyte influx into the anterior eye chamber increased between 2 and 4 h after FMLP instillation, peaking between 4 and 6 h, then resolving after 8 h. Ibuprofen inhibited leukocyte accumulation into the anterior eye chamber in a dose dependent fashion with a maximum (90.0 +/- 1.4%, X +/- SEM) inhibition with 70 mg/kg/day and an ID50 of 8 mg/kg/day. In conclusion, the anterior eye chamber FMLP-stimulated leukotaxis assay is useful to evaluate the role of pharmacologic agents. Here, ibuprofen was found to inhibit leukotaxis in a dose-dependent manner.

Animals↗
PubMed1984

Alteration of human follicular fluid plasminogen activator activity by ovarian hyperstimulation.

Recently, it has been shown that granulosa-cell secretion of plasminogen activator (PA) is responsive to luteinizing hormone (LH)/human chorionic gonadotropin (hCG) as well as follicle stimulating hormone (FSH) in the rat and the pig. Accordingly, we asked whether PA activity in follicular fluid from exogenously stimulated human follicles was different from that of normal cycles and whether or not these activities correlated with follicular maturation as determined by follicular fluid steroid concentration. Follicular aspirates were obtained from women who were participating in an in vitro fertilization protocol. Follicular fluid concentrations of estradiol and progesterone were determined by established radioimmunoassay. PA activity, determined using a modified indirect solid-phase radioassay, was significantly less in follicles from patients treated with human menopausal gonadotropin (hMG) plus clomiphene (P less than 0.05) compared to untreated patients or those receiving hMG or clomiphene alone. Correlations of PA activity and follicular fluid steroid concentrations demonstrated no significant correlation in samples from treated patients. In contrast, untreated spontaneously cycling patients had a significant (r = 0.89, P less than 0.05), positive correlation between follicular fluid estradiol levels. There was no correlation between PA activity and follicular fluid progesterone levels in any of the groups. These results suggest that a subtle balance in granulosa-cell secretion of PA and steroid exists, which appears to be disrupted by follicular hyperstimulation during treatment of patients participating in in vitro fertilization protocols.

Adult↗
PubMed1981

Follicular phase treatment of luteal phase dysfunction.

Previously, we demonstrated that selective suppression of serum follicle-stimulating hormone (FSH) in monkeys treated with charcoal-extracted porcine follicular fluid (pFF) in the early follicular phase induced luteal defects resembling those which occur spontaneously in women and monkeys. Here, we assessed whether luteal phase defects arising in association with induced FSH deficiencies during the early follicular phase can be treated by early FSH therapy. Rhesus monkeys were treated with pFF and human menopausal gonadotropin (hMG) (FSH:luteinizing hormone [LH], 3:1) on cycle days 1 to 3 or day 4, respectively. Daily femoral blood samples were analyzed for LH, FSH, and estradiol by radioimmunoassay. In the monkeys treated with the pFF-hMG combination, a single ovulation was uniformly noted at laparoscopy, and initial luteal phase elevations in serum progesterone levels were nearer those of normal ovulatory cycles than after pFF alone. These results suggest that FSH/LH treatment in the early follicular phase compensated, in part, for the pFF-induced deficiency in endogenous FSH levels.

Animals↗
PubMed1980

Endometriosis: role of ovarian steroids in initiation, maintenance, and suppression.

Although endometriosis is commonly associated with infertility, the hormonal requirements for its spontaneous initiation and maintenance remain unknown. Since endometriosis occurs in the monkey, these primates are useful for examining the hormonal dependencies of endometrial plaques. Sequential estradiol and progesterone in Silastic capsules were placed subcutaneously into long-term castrated monkeys (N = 26). Blood samples obtained biweekly were assayed for progesterone and estradiol by radioimmunoassay. Three weeks later, endometriectomies were performed and the minced endometrium was "seeded" into the peritoneal cavity. Thereafter, monkeys were divided into four groups: (1) control, received no therapy; (2) received only estradiol capsules; (3) received only progesterone capsules; and (4) received both estradiol and progesterone capsules. All monkeys underwent laparotomy 4, 12, and 16 weeks after endometrial transplantation to determine whether viable endometrial plaques were present. After 4 weeks, endometriosis was found in all groups, including the controls. At 12 and 16 weeks, monkeys treated with both estradiol and/or progesterone contained viable endometrial plaques, whereas monkeys without steroid supplementation contained only "burnt out" plaques, that is, nonviable endometrial tissue. In conclusion, endometrial tissue transplanted into the peritoneum required no steroid supplementation for initiation. However, once implanted, either estradiol or progesterone, alone or in combination, was required for maintenance. These findings suggest that successful treatment of endometriosis may require both the eradication of existing endometrial plaques and the prevention of reseeding over the peritoneum resulting from retrograde menstruation.

Animals↗
PubMedDate not supplied

Alterations of angiotensin II receptor levels in full-thickness excisional wounds in rat skin.

Angiotensin II was recently shown to have a growth-promoting role after vascular injury and in the development of cardiac hypertrophy and fibrosis. In addition, angiotensin II may play a role in dermal wound repair. In this article, alterations in angiotensin II receptor levels in tissue harvested from full-thickness excisional dermal wounds in adult Sprague-Dawley rats were examined. A 2.25 cm(2) full-thickness excision of the dorsal skin was made under general anesthesia, and the tissue was harvested on days 1, 3, 5, 7, and 10 after wounding. The level of (125)I-Sar(1).IIe(8)-angiotensin II bound to membrane preparations of both granulation tissue and wound edge increased from day 1, peaked on day 5, and returned to nonsurgical levels by day 10. In both granulation and wound edge segments of the injured skin, the maximum binding on postoperative day 5 was about twice that of postoperative day 1 tissue or control skin. Competitive binding studies with angiotensin II type 1 receptor or type 2 receptor antagonists (DuP 753 and CGP 42112B, respectively) showed that the receptors present in the healing dermal tissue from the adult rat were almost entirely of the type 1 receptor form.

Journal Article↗
PubMedDate not supplied

Time-dependent effect of tolmetin sodium in a rabbit uterine adhesion model.

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) that reduces adhesion formation in several animal models after a single intraperitoneal (i.p.) dose delivered at the time of surgery. We set out to determine the period during which tolmetin could prevent adhesions. Adhesions were induced in New Zealand White rabbits (2-3 kg) by abrading the uterine horns and removing their mesouterine vasculature. Tolmetin sodium (1 mg/5 ml saline) was given at various times relative to the start of surgery as a single dose i.p. One week later adhesions were assessed using a standard scoring system (0 = no adhesions; 1 = light adhesions involving both uterine horns; 2 = more tenacious adhesions to bowel or bladder; 3 = tenacious adhesions to bowel and bladder partly immobilizing the uterus; 4 = completely fixed horns adherent to bowel and bladder). Scores were arranged in ascending rank order. Mean rank positions were calculated for each group and compared against controls (Dunnett's multiple comparison). Tolmetin sodium was most effective when administered within 1 hour of surgery. Mild effects could still be observed after 4 hours and the effect diminished after 24 hours. When these effects are compared to the temporal biochemical and cellular effects of tolmetin obtained in related studies, the data support the hypothesis that tolmetin reduces adhesions at least in part by modulating fibrinolytic activity of resident macrophages and macrophages present in the early postsurgical period.

Animals↗
PubMedDate not supplied

Comparative efficacy of nonsteroidal anti-inflammatory drugs and anti-thromboxane agents in a rabbit adhesion-prevention model.

A variety of nonsteroidal anti-inflammatory drugs (NSAIDs) has been found to inhibit postsurgical peritoneal adhesion formation in a number of animal models. A rabbit uterine horn adhesion model was used to directly compare several commonly used NSAIDs of different chemical classes in a single animal study to evaluate their ability to prevent adhesion formation. The effect of thromboxane inhibitors on adhesion prevention was also evaluated. Each of the NSAIDs tested (tolmetin, ibuprofen, aspirin, and indomethacin) showed significant and comparable efficacy. In this same study, imidazole, a thromboxane synthetase inhibitor, also showed significant efficacy. In a second study, ridogrel, an inhibitor of thromboxane synthetase as well as a thromboxane A2 receptor blocker, also showed significant efficacy in reducing peritoneal adhesion severity. These results further support the view that NSAIDs act to prevent adhesions through a common mechanism. In addition, thromboxane A2 inhibitors were also shown to be efficacious in adhesion prevention, suggesting that platelets may play a substantial role in adhesion formation.

Animals↗
PubMedDate not supplied

Alterations of angiotensin II Receptor levels in sutured wounds in rat skin.

Angiotensin II receptor levels have been shown to vary with postoperative time in tissue harvested from full-thickness dermal excisional wounds on adult rats. This study examined the expression of AII receptors in a sutured wound model. Two full-thickness incisional wounds were made in the dorsal skin of adult Sprague-Dawley rats and sutured immediately under general anesthesia. The wound tissues were harvested at 0, 0.5, 1, 2, 4, 24 h and on days 2, 3, 4, 5, 7, and 10 after the wounding. The levels of 125I-Sar1.Ile8-AII bound to membrane preparations of the wound tissues decreased at early time points (from 0.5 to 4 h), increased from day 1 to day 7, and returned to nonsurgical levels by day 10. Competitive binding studies showed that the receptors were predominantly of the AT1 receptor subtype. These results suggest that an immediate and transient reduction in AII receptor expression occurred after wounding, followed by an increase in the number of AII receptors that was maintained for 5 to 7 days postoperatively. Because these data are consistent with those observed after excisional wounding, temporal changes in AII receptor expression may be integral to the process of wound healing.

1-Sarcosine-8-Isoleucine Angiotensin II↗