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Biomedical subjects

G H Nelson

Publications and source records attributed to G H Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1988

In vivo effect of methylene blue on endothelium-dependent and endothelium-independent dilations of brain microvessels in mice.

Arterioles on the surface of the mouse brain were observed by in vivo TV microscopy. Four dilators were topically applied to relax the vessels in vivo. Two of the dilators were acetylcholine and bradykinin, whose action in this vascular bed is dependent upon production of endothelium-dependent relaxing factors. The other two dilators were sodium nitroprusside and 8-bromo-cGMP, whose action is not endothelium dependent. The dilations by acetylcholine, bradykinin, and nitroprusside were significantly depressed by 10(-4) M methylene blue applied topically for 7 minutes prior to application of the dilators. The inhibitory effect was reversible, was greatest against acetylcholine, and was least against nitroprusside. These data parallel reports of methylene blue's action against these dilators when applied to large blood vessels in vitro. Our data appear to be the first microvascular data and the first in vivo data showing this effect. The data thus suggest that the mechanisms underlying dilation of cerebral arterioles and large extracerebral vessels are similar. The literature accounts for the effect of methylene blue on the basis of its action as an inhibitor of guanylate cyclase. Our data, including the failure of methylene blue to alter dilation by 8-bromo-cGMP, are in keeping with this hypothesis and with current beliefs that guanylate cyclase and cGMP have a central role in vasodilation. The data do not rule out the possibility that methylene blue has an additional action in the case of acetylcholine and inactivates the endothelium-dependent relaxing factor for that dilator.

Acetylcholine↗
PubMed1988

Endothelium-dependent constriction demonstrated in vivo in mouse cerebral arterioles.

Endothelium-dependent constriction in mouse pial arterioles was demonstrated by testing contractile responses before and after endothelial injury. All responses were monitored at the same site as the injury. Injury was produced in vivo by exposing an arteriole on the brain surface to the beam of a 6-mW helium-neon laser after first sensitizing the microvascular bed to the laser energy by injecting Evans blue intravenously. The contractile response to serotonin creatinine sulfate (20 micrograms/ml) and to sodium arachidonate (30 micrograms/ml) was monitored in vivo with an image splitter and TV microscope. The responses before laser injury were always constriction; the responses after laser injury were always relaxation. After laser injury, acetylcholine chloride (80 micrograms/ml) constricted every vessel tested at the injured site. Thus, the injured segment had not lost the capacity to constrict even though neither serotonin nor arachidonate remained able to induce a constriction. The endothelium-dependent constrictions to serotonin or arachidonate were also blocked by pretreatment of the mouse with cyclooxygenase inhibitors, acetylsalicylic acid (100 mg/kg i.p.) or indomethacin (5 mg/kg). The data suggests that endothelium-dependent constriction to serotonin is mediated by release of arachidonate from the endothelial cell and conversion of that arachidonate by cyclooxygenase to some constricting prostanoid.

Animals↗
PubMed1988

Endothelium dependence of dilation of pial arterioles in mouse brain by calcium ionophore.

Previous studies have shown that local selective in situ injury of pial arteriolar endothelium eliminates the dilations produced by acetylcholine or bradykinin. One means of producing such injury employs a helium-neon laser in the presence of intravascular Evans blue. Since the endothelium-dependent dilations produced by acetylcholine or bradykinin may be initiated by interaction with endothelial surface receptors, it is possible that the light simply inactivates or destroys these receptors. We used calcium ionophore A-23187, another dilating agent known from in vitro studies of large arteries to be endothelium-dependent, which moves calcium into endothelial cells rather than interacting with surface receptors. Our data in 10 mice show that before injury, 10(-5)M A-23187 dilated arterioles to 109 +/- 2% of control diameter. After selective endothelial injury by helium-neon laser, dilation was essentially abolished (101 +/- 1% of baseline diameter; p less than 0.01, Wilcoxon test). Undamaged sites along the arteriole still dilated to A-23187. Our data indicate that the laser must do more than inactivate surface receptors and are the first in vivo microvascular (vessels of less than 100 micron diameter) data showing endothelium dependence of the response to A-23187.

Animals↗
PubMed1987

Effects in mice of testosterone and dihydrotestosterone on platelet aggregation in injured arterioles and ex vivo.

Mice were implanted subcutaneously with placebo pellets, or with pellets containing either testosterone (T) or dihydrotestosterone (DHT). Eight to 19 days later platelet aggregation was produced in pial or mesenteric arterioles by injuring their endothelium with a noxious light/dye stimulus. The onset of platelet aggregation was significantly shortened in the mesenteric arterioles of male mice following implantation of 1.0 mg T or 0.1 mg DHT. However no effect was observed in females, nor did T or DHT alter aggregation in pial arterioles of either sex. Ex vivo studies showed that sodium arachidonate produced greater aggregation of platelets in plasma from testosterone treated males compared with controls. No effect of testosterone was observed ex vivo in platelets from females. These ex vivo results paralleled in vivo data from mesenteric vessels, but not from pial vessels. Moreover DHT failed to influence aggregation ex vivo in either sex. Thus enhanced aggregation observed in vivo in mesenteric arterioles of androgen treated males may not reflect direct action of androgen on the platelet. Rather enhanced aggregation may reflect hormonal action on endothelium or adjacent tissue. In addition to the preceding studies we tested the hypothesis that testosterone's action was due to its conversion to estradiol. This was considered because our data with T and mesenteric vessels resembled that previously reported by us with estradiol. However only minimal elevations in plasma estradiol levels resulted from testosterone treatment.

Animals↗
PubMed1987

The reliability and clinical use of a rapid phosphatidylglycerol assay in normal and diabetic pregnancies.

Lecithin phosphorus concentration, the standard fetal lung maturity test in our institution, and phosphatidylglyercol were assayed in 69, 29, and 45 amniotic fluid samples from normal (GI), gestational (GII), and insulin-dependent diabetic (GIII) women by means of thin layer chromatography and Amniostat-FLM, respectively. Lecithin phosphorus concentration greater than or equal to 0.1 mg/dl and positive or strong positive Amniostat-FLM results were considered mature. The results of both assays were concordant in 79% of the samples. The discordance rate was highest in GIII patients. In our experience, respiratory distress syndrome did not develop in neonate infants of diabetic women delivered after a mature lecithin result. With lecithin phosphorus concentration as the reference standard, the predictive value of a mature Amniostat-FLM result was 96.2%, whereas that of an immature result was 58.5%. Respiratory distress syndrome occurred in only two GIII neonates who were delivered within 72 hours of both immature lecithin and Amniostat-FLM results. These findings support the use of Aminostat-FLM as a screening test for fetal lung maturity in both normal and diabetic pregnancies. Additional tests will be necessary to evaluate further fetal lung maturity only if the results are negative.

Adult↗
PubMed1987

Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse.

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.

Acetylcholine↗
PubMed1986

Effect of maternal-fetal disorders on lung maturation. I. Diabetes mellitus.

Amniotic fluid for fetal lung maturity studies was obtained from 287 healthy and 198 diabetic women. Classes of diabetes were as follows: Class A, 111; Class B, 58; Class C, 13; Class D, 11; Class F, 4; and Class R, 1. The regression lines representing the relationship of amniotic fluid lecithin phosphorus concentration to gestational age at amniocentesis in each of the groups of diabetic patients were not statistically different from those of the control subjects. Each of the diabetic patients was then matched with a control subject of the same race, sex of newborn infant, and gestational age at amniocentesis. The regression lines of the nonhypertensive, hypertensive, and all diabetics were not different from those of their respective matched control subjects. Also there was no difference in the proportion of mature lecithin phosphorus concentrations at different weeks between diabetic and normal women. The absence of a significant influence of diabetes on fetal lung maturation is probably due to improvement in diabetic control resulting in normalization of the fetal metabolic environment.

Amniocentesis↗
PubMed1986

Blood loss at vaginal delivery.

Although the accurate assessment of blood loss at vaginal delivery is clinically important in terms of maternal morbidity and mortality, the quantity is usually underestimated. We present a simple, practical, and convenient method of quantitating blood loss at vaginal delivery. The method of vaginal delivery (spontaneous versus forceps) does not significantly affect blood loss; an episiotomy, a laceration, or both may.

Amniotic Fluid↗
PubMed1985

Indications for and timing of delivery in diabetic pregnancies.

The management of 430 diabetic pregnancies is presented. Our protocol emphasized "tight" metabolic control and assessment of fetal well-being by antepartum fetal heart rate testings and estriol levels. Spontaneous labor was allowed in uncomplicated Class A diabetic patients. Labor in complicated cases and insulin-dependent diabetic pregnancies was induced after establishing fetal lung maturity, except when a maternal or fetal complication dictated otherwise. A significant drop in estriol was observed in 4% of Class A diabetic patients and 10.2% of insulin-dependent diabetic patients. None developed a positive contraction stress test. Abnormal fetal well-being tests contributed minimally to the indications for induction of labor. The incidence of induced preterm delivery was 2.8% in Class A diabetic patients and 18.4% in insulin-dependent diabetic ones. The perinatal mortality was 5.6:1000 and 13:1000, respectively. The incidence of respiratory distress syndrome was very low, and none of the cases were associated with a "mature" amniotic fluid lecithin phosphorus measurement.

Adult↗
PubMed1985

Effects of estradiol on platelet aggregation in mouse mesenteric arterioles and ex vivo.

Mice were implanted subcutaneously with a pellet containing 0.5 mg estradiol or with a placebo. Eight to 12 days later platelet aggregation was produced in mesenteric arterioles by injuring their endothelium in vivo with a noxious light/dye stimulus. The time between the onset of the noxious stimulus and the appearance of platelet aggregates was significantly shortened (p less than .01) in the estradiol treated mice. In contrast to this enhancement of aggregation, when platelets were tested ex vivo in platelet rich plasma (PRP), aggregation to sodium arachidonate was inhibited in estradiol treated mice. Aggregation of PRP by ADP was not affected by estradiol treatment of the mice. Thus the enhanced aggregation observed in injured mesenteric arterioles of estradiol treated mice may not reflect direct effects of estradiol on the platelet itself. Rather enhanced aggregation may reflect an effect of estradiol on endothelium or adjacent tissue. The data are discussed in light of other literature concerning estradiol effects in rodents, and in light of literature suggesting that an increased number of thromboembolic events occurs in humans receiving high doses of estrogens.

Adenosine Diphosphate↗
PubMed1985

Theoretical effects of amniotic fluid volume changes on surfactant concentration measurements.

A baseline model for consideration of the theoretical effects of amniotic fluid volume changes on surfactant concentration measurements has been constructed. The baseline data include: a polynomial equation that best fits experimental data comparing amniotic fluid lecithin concentration measurements to gestational age, inflow of 0.450 L of surfactant-poor fluid into the amniotic fluid per day, outflow of 0.450 L of surfactant-rich fluid per day, and volume of 1.0 L of amniotic fluid between 30 to 31 and 38 to 39 weeks' gestation. With this model the incremental amounts of lecithin necessary to achieve the concentration levels derived from the polynomial equation have been calculated. The quantity of lecithin needed was calculated at intervals of 0.1 day for 56 days. Polyhydramnios and oligohydramnios were then allowed to develop hypothetically by modifying the inflow or outflow of fluid while keeping the quantity of lecithin added exactly the same as was determined from the baseline data. Chronic polyhydramnios or oligohydramnios had minimal effects on the concentration measurements. The effects of acute polyhydramnios (or oligohydramnios) were greater when the change in volume was due to an increased (or decreased) volume of inflow as compared to a decreased (or increased) volume of outflow.

Acute Disease↗
PubMed1985

The unreliability of amniotic fluid bilirubin measurements in isoimmunized pregnancies in sickle cell disease patients.

Amniotic fluid spectrophotometric analysis for bilirubin (delta optical density [delta OD450], at 450 nm) is used to assess the severity of fetal involvement in isoimmunized pregnancies. Two patients presented with sickle cell anemia and hyperbilirubinemia who also were isoimmunized. The first patient had anti-kell and anti-e antibodies, whereas the second patient had anti-Lewisa and anti-Coltonb antibodies. Delta OD450 was elevated in both patients. The difficulty in interpretation of high delta OD450 in the presence of maternal hyperbilirubinemia is stressed. Sickle cell diseased patients are particularly prone to present with this problem. These patients always have hyperbilirubinemia and a relatively high incidence of irregular antibodies because of the numerous blood transfusions they receive. The management of these two patients is presented with suggestions for the use of alternative modalities of monitoring isoimmunized pregnancies in patients with hyperbilirubinemia.

Adult↗
PubMed1983

Some properties of mouse platelets.

Mouse platelets were aggregated by arachidonate, thrombin, collagen and ADP. In general they were, like rat platelets, more aggregative in heparinized PRP than in citrated (3.8%) PRP. Mouse platelets underwent the release reaction when aggregated by arachidonate, collagen and thrombin, but not when stimulated by ADP. The aggregation of the platelets to arachidonate was inhibited by cyclooxygenase inhibitors and by prostacyclin. Studies with tritiated arachidonate showed that mouse platelets possess the lipoxygenase and cyclooxygenase pathways found in other mammalian platelets and produce thromboxane and 12-HETE. The mouse provides a convenient model for the study of many conditions known to affect platelet aggregation. The similarity of mouse platelets to the platelets of other mammals together with the ability to study large numbers of animals at low cost, should encourage further use of mouse platelets.

Adenosine Diphosphate↗