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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 181 records · Page 10Linked to original sources
PubMed1991

Hemorrhagic shock and bacterial translocation in a swine model.

Bacterial translocation is proposed as an explanation for sepsis associated with hemorrhagic shock. This study attempted to document these events in a large animal model. Male swine were randomly assigned to control (n = 10) or experimental (n = 10) groups. Animals were anaesthetized, and the bladder, portal vein, and a mesenteric lymphatic vessel cannulated. Experimental animals were bled 40% of blood volume. Over the next six hours maintenance fluids were given, and cultures of portal blood and mesenteric lymph taken. Before the swine were killed, cultures were taken from portal and systemic blood, mesenteric lymph, and lymph nodes, and a portion of terminal ileum was resected for histologic study. Experimental animals experienced significant shock as demonstrated by changes in hemodynamic and biochemical variables. Cultures and histologic examination of the terminal ileum showed no significant difference between control and experimental animals. In an unresuscitated swine model, significant bacterial translocation was not demonstrated within six hours of hemorrhagic shock.

Animals↗
PubMed1991

Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism.

Our objective was to find out if central injection of neuropeptide Y (NPY) would alter brown fat thermogenesis and white fat lipoprotein lipase activity. The following three groups of Sprague-Dawley rats received five injections over 24 h into the right lateral ventricle: 1) NPY (5 micrograms/injection) and ad libitum food; 2) NPY (5 micrograms/injection) and food restricted to control intake; 3) saline injection and ad libitum food. The NPY ad libitum-fed group consumed more food than the saline controls or NPY food-restricted animals. Brown fat thermogenic activity, assessed by GDP binding, was decreased relative to saline controls in both NPY-treated groups. White fat lipoprotein lipase activity was greatly increased in both NPY treatment groups compared with saline controls. The NPY effects on brown and white fat were not explained by measures of serum insulin, glucagon, glucose, or other metabolites. In a follow-up experiment, we asked whether food was necessary for expression of the NPY effects. Brown fat mitochondrial GDP binding indicated NPY effect even when no food was ingested. We conclude that intracerebroventricular administration of NPY promotes white fat lipid storage and decreases brown fat thermogenesis in addition to its known effect of stimulating food intake.

Adipose Tissue↗
PubMed1991

Food deprivation-induced vs. drug-induced feeding: a behavioral evaluation.

Several neuroactive substances including neuropeptide Y (NPY), muscimol, and norepinephrine (NE) stimulate feeding in satiated rats. In the present study, we observed the behavioral patterns of rats stimulated to eat by food deprivation or by intracerebroventricular (icv) injection of orexigenic agents to explore the hypothesis that such agents produce a behavioral state resembling hunger. Animals that were food deprived for 24 h spent the majority of their time eating (35%), drinking (5%), resting (44%), and moving (13%) when food was available. If food was removed and substituted with a chewable substrate (plastic tube), they chewed on tubes for a brief period (5%) but spent most of their time moving (14%) or resting (77%). In the absence of food or tubes, they briefly moved about the cage (4%) and spent almost all of their time resting (94%). The patterns observed with the orexigenic drugs were different, particularly in the absence of food. NPY-injected rats were more active than deprived rats, spending 22% of their time moving in the presence of food, 47% in the presence of tubes, and 37% in the absence of food or tubes. Rats injected with muscimol demonstrated a marked increase in the time spent chewing and eating. These rats spent 67% of their time eating in the presence of food and chewed 25% of the time in the absence of either food or tubes. NE-injected rats also chewed when tubes were present (17%) or when no food or tubes were present (10%). Lag sequential analysis further documented differences in behavioral patterns amongst the various treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of 21-aminosteroid U-74006F on lipid peroxidation in subarachnoid clot.

The present study was undertaken to investigate the effect of U-74006F on malondialdehyde (a by-product of lipid peroxidation) in subarachnoid clot. Eighteen cynomolgus monkeys were divided into three groups of six each. There were two U-74006F-treated groups, receiving doses of 0.3 or 1.0 mg/kg, and a placebo-treated group. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and placement of subarachnoid clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after the experimental subarachnoid hemorrhage (SAH), angiography was repeated and the animals were killed. In the placebo-treated group, significant vasospasm occurred in the MCA on the side of the clot (p less than 0.01). After U-74006F treatment at both dosages, significantly less vasospasm developed in the clot-side MCA (p less than 0.01). The content of malondialdehyde was measured by both the thiobarbituric acid test and high-performance liquid chromatography (HPLC). Comparing the two methods, HPLC proved to be more accurate than the thiobarbituric acid test, especially for measurement of low concentrations of malondialdehyde. In the placebo-treated group, the malondialdehyde content was significantly increased in the Day 7 clot (p less than 0.05). In contrast, malondialdehyde content in freshly prepared clot was very low. In the 0.3-mg/kg U-74006F group, the malondialdehyde content of clot was significantly less at Day 7 compared to clot from the placebo-treated group (p less than 0.05). Although the malondialdehyde content of clot from the 1.0 mg/kg U-74006F-treated group was less than that of placebo, it was not significantly so. Malondialdehyde was not detected in the actual vessel wall of the MCA of any group. These results suggest that lipid peroxidation in subarachnoid clot may play a role in the pathogenesis of vasospasm and that the salutary effects of U-74006F in vasospasm may be mediated by a reduction of lipid peroxidation in SAH.

Animals↗
PubMed1990

Nor-binaltorphimine decreases deprivation and opioid-induced feeding.

We evaluated the effect of the kappa antagonist, nor-binaltorphimine (nor-BNI) on deprivation and opioid-induced feeding in rats. Intracerebroventricular administration of nor-BNI (100 nmol) decreased deprivation-induced feeding for as long as 24 h, albeit in a fairly weak manner (maximum decrease of approximately 28%). Nor-BNI (1, 10 and 100 nmol) decreased feeding induced by the kappa ligand U-50,488H by as much as 85% during the first hour of the study. This kappa antagonist also decreased feeding induced by the delta agonist DSLET and the mu agonist DAMGO. Based on previous studies indicating that nor-BNI is a selective kappa antagonist, we conclude that not only U-50,488H (kappa), but also DSLET (delta) and DAMGO (mu)-induced feeding are dependent upon an active kappa receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

The effect of centrally administered naloxone on deprivation and drug-induced feeding.

In the present study we evaluated the effect of intracerebroventricular (ICV) administration of naloxone on feeding induced by food deprivation, norepinephrine (NE), muscimol and neuropeptide Y (NPY). Naloxone (200, 100 and 50 micrograms ICV) decreased deprivation-induced feeding. In contrast, only the 200 micrograms dose of naloxone decreased NE-induced feeding and the 200 and 100 micrograms doses decreased muscimol-induced feeding. Eating stimulated by central administration of NPY was potently decreased by doses of naloxone ranging from 10-200 micrograms.

Animals↗
PubMed1990

The effect of timing of intrathecal fibrinolytic therapy on cerebral vasospasm in a primate model of subarachnoid hemorrhage.

The effect of intrathecal tissue plasminogen activator administered at times from 0 to 72 hours after subarachnoid hemorrhage on the development of cerebral vasospasm in primates was examined. Thirty monkeys were randomly assigned into one of five equal groups: a control group that underwent subarachnoid hemorrhage alone, and 0-, 24-, 48-, and 72-hour treatment groups that received 0.75 mg of tissue plasminogen activator at those times after baseline cerebral angiography and subarachnoid hemorrhage on the right side. Seven days later angiography was repeated and the animals were killed. One animal in the 72-hour group developed a delayed ischemic deficit on Day 7 after subarachnoid hemorrhage. In the control and 72-hour groups significant vasospasm occurred in most of the major, right cerebral arteries (P less than 0.05), but no significant vasospasm developed in the 0-, 24-, and 48-hour groups. Although a large subarachnoid clot remained in the control animals, most clot had been dissolved in all treatment groups. Lysing of subarachnoid hematoma with intrathecal tissue plasminogen activator within 72 hours of subarachnoid hemorrhage is effective in preventing vasospasm in primates.

Animals↗
PubMed1990

A dosage study of the effect of the 21-aminosteroid U74006F on chronic cerebral vasospasm in a primate model.

The efficacy of the 21-aminosteroid U74006F was investigated using different dosages in a restricted, randomized, placebo-controlled trial. Forty cynomolgous monkeys were divided into five groups of eight. There were two groups given treatment with placebos, one being saline and the other the vehicle in which U74006F was delivered. There were three U74006F treatment dosage groups: 0.3, 1.0, and 3.0 mg/kg. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and subarachnoid placement of a clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after experimental subarachnoid hemorrhage, angiography was repeated, and the animals were killed. In both saline or vehicle placebo treatment groups, significant vasospasm (VSP) occurred on the clot side in the extradural internal carotid artery (C3), the intradural internal carotid artery, the precommunicating segment of the anterior cerebral artery (A1,) and the MCA (P less than 0.01). After U74006F treatment, significantly less VSP developed in the A1 on the clot side (0.3 mg/kg U74006F treatment group) and the MCA (all U74006F treatment groups, P less than 0.05). When the percentages of change from the baseline for the vessel diameters on the clot side were compared, VSP was attenuated in the A1 (P less than 0.05) and MCA (P less than 0.001) of all U74006F treatment groups as compared with the placebo treatment groups. Only 0.3 mg/kg of U74006F significantly prevented VSP in C3 (P less than 0.01). Although the 0.3 mg/kg dosage appeared to have the most favorable effect, no significant differences were observed among the three dosage groups. Electron microscopy of the MCA on the clot side in the animals treated with U74006F still showed luminal convolutions and morphological changes in the endothelial cells. These changes appeared less prominent in those MCAs with milder VSP. If these results in primates are applicable to humans, U74006F would be useful in reducing VSP after aneurysmal subarachnoid hemorrhage.

Animals↗
PubMed1989

Usefulness of sustained-release diltiazem for stable angina pectoris.

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.

Adult↗
PubMed1989

Effect of breast-feeding on immune response to BCG vaccination.

The effect on BCG immunisation of feeding either formula or breast milk was assessed in Canadian Cree infants who were vaccinated either at birth or after 1 month of age. The response to BCG was measured in terms of lymphocyte blastogenesis stimulated by purified protein derivative of Mycobacterium tuberculosis. Breast-feeding significantly enhanced cell-mediated immune response to BCG vaccine given at birth, but had no significant effect if vaccine was given after 1 month. These findings were not related to maternal history of tuberculosis or BCG vaccination, and the feeding method did not influence lymphocyte stimulation by candida or streptococcal antigens.

Age Factors↗
PubMed1989

The adenosine agonist N6-R-phenylisopropyladenosine (R-PIA) stimulates feeding in rats.

Administration of adenosine and agonists of the adenosine receptors to rats results in hypoactivity, hypothermia, muscle relaxation and antinociception. In the present study, we found that the adenosine ligand, N6-R-phenylisopropyladenosine (R-PIA), increased food intake in rats at a time in the day when rats normally eat very little food or none at all. Feeding was not reliably stimulated upon the first exposure to R-PIA, but was clearly increased following repeated administration of this agonist. Other adenosine agonists, namely 2-chloradenosine and 5'N-ethylcarboxamide adenosine, failed to alter feeding after a single injection or after repeated exposure. The adenosine antagonist, caffeine, did not block R-PIA's effect on food intake, whereas the opioid antagonist, naloxone, blocked R-PIA-induced eating. These data suggest that R-PIA stimulates feeding independent of the A1 or A2 adenosine receptors.

2-Chloroadenosine↗
PubMed1989

A multicenter randomized trial of ionic (ioxaglate) and nonionic (iopamidol) low-osmolality contrast agents in cardiac angiography.

A multicentered double-blind randomized study was performed comparing the electrocardiographic and hemodynamic changes induced by two new low osmolar contrast agents used for cardiac angiography. The low osmolar ionic (ioxaglate) contrast agent was compared with a low osmolar nonionic (iopamidol) contrast agent in 150 patients with angina pectoris undergoing angiography. Systolic blood pressure, left ventricular end-diastolic pressure, heart rate, and QT interval were measured just before and for 90 s following the left ventricular angiography and selective coronary angiography. Each group was also evaluated for adverse events and quality of radiographic images. Following left ventricular angiography, the systolic blood pressure dropped slightly in both groups with a greater decrease seen in the iopamidol group at 5 s (p less than 0.05). After selective right and left coronary angiography, systolic blood pressure decreased transiently and equally in both treatment groups. The left ventricular end-diastolic pressure increased after the ventriculogram in both groups (15.9 +/- 6.3 to 18.9 +/- 8.6 mmHg in the ioxaglate group and 16.1 +/- 6.7 to 20.1 +/- 7.8 mmHg in the iopamidol group), the change being significant only in the iopamidol group (p less than 0.05). Heart rate increased slightly but significantly in the ioxaglate-treated patients following left ventricular angiography (71.4 +/- 15.2 to 74.4 +/- 13.7 beats/min) (p less than 0.01). QT interval transiently increased following left ventriculography with ioxaglate (407 +/- 59.5 to 420 +/- 58.3 ms) (p less than 0.05) compared with iopamidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists.

The potencies of several opioid agonists are reduced in diabetic animals and in animals made hyperglycemic via injections of glucose. In this report we examined the effects of streptozotocin-induced diabetes on the feeding responses to centrally administered opioid agonists with differing receptor selectivities. The selective mu receptor agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO) caused a larger increase in intake in diabetic rats than in controls. In both groups feeding responses were greater on the fourth day of daily injections than on the first day. The delta receptor agonist [D-Ser2,Leu5]-enkephalin-Thr6 (DSLET) stimulated intake in controls but not in diabetics. However, the elevated baseline and large variability in intake of the diabetics in this experiment prevent drawing a conclusion on diabetes-induced changes in the potency of this peptide. No differences between controls and diabetics were apparent in the feeding responses to U50, 488H, a selective kappa receptor agonist. These data suggest that diabetes may differentially affect the classes of opioid receptors or the binding of ligands to these receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Herpes labialis treatment with acyclovir 5% modified aqueous cream: a double-blind randomized trial.

The efficacy of 5% acyclovir in a modified aqueous cream vehicle (ACV-MAC) in the treatment of recurrent herpes labialis was tested in a randomized, double-blind clinical trial with the modified aqueous cream vehicle as a control medication. The ACV-MAC formulation has previously been shown to offer superior cutaneous absorption relative to other topical acyclovir formulations. Treatment was initiated by patients within 1 hour of prodrome in an attempt to maximize clinical impact of this virustatic drug. While the patient group receiving active drug showed a trend toward accelerated healing, no significant differences for lesion or healing characteristics could be measured between the two treatment groups. It is suggested that optimal efficacy of ACV-MAC may be predicated on prophylactic treatment, that is, "trigger"-initiated rather than prodrome-initiated treatment.

Acyclovir↗
PubMed1989

Intrathecal fibrinolytic therapy after subarachnoid hemorrhage: dosage study in a primate model and review of the literature.

Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currently investigating intrathecal thrombolytic therapy with human, recombinant, tissue plasminogen activator (rt-PA) in a primate model of subarachnoid hemorrhage (SAH) and cerebral vasospasm (VSP). In the present study 16 monkeys were divided into 4 groups of 4, and each group received a different dose of sustained-release gel rt-PA at the time of experimental SAH. Cerebral angiography seven days later showed that whereas no VSP occurred in the groups receiving 0.5 or 0.75 mg of rt-PA, mild to moderate VSP occurred in the groups receiving 0.125 or 0.25 mg of rt-PA. Analysis of the combined 2 smaller dosage groups revealed significant (P less than 0.05) reduction of lumen caliber in the clot-side internal carotid (C3 and C4), proximal anterior cerebral (A1) and middle cerebral (MCA) arteries. Gross subarachnoid clot remained in all of the animals in the 0.125 and 0.25 mg dose groups, in 2 of the animals in the 0.5 mg dose group, and none of the animals in the 0.75 mg dose group. It was concluded that 0.75 mg of gel rt-PA is sufficient to completely lyse a 4.25 ml SAH and prevent VSP in our primate model. The literature on fibrinolysis and erythrocyte clearance in cerebrospinal fluid (CSF) is reviewed.

Animals↗