Search PubMed⌕ Search

Biomedical subjects

W R Anderson

Publications and source records attributed to W R Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1988

Evidence for suppression of serum LH without elevation in serum estradiol or prolactin with a brain-enhanced redox delivery system for estradiol.

We developed a redox system for brain-enhanced delivery of estradiol based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Estradiol (E2), when combined with the lipoidal carrier, readily crosses the blood-brain barrier. The carrier, when oxidized, reduces the rate of exit of the estradiol-carrier complex from the brain. Subsequent hydrolysis of the carrier provides sustained production of estradiol in the brain. The aim of the study was to evaluate the effects of single vs. multiple injections of the estradiol-chemical delivery system (E2-CDS) on both central and peripheral estrogen-responsive tissues. Ovariectomized Sprague-Dawley rats received an intravenous injection of E2-CDS at 10, 33, 100 or 333 micrograms/kg BW or the drug vehicle, dimethyl sulfoxide (DMSO; 0.5 ml/kg) every 2 days for 7 injections (2 weeks) or a single injection only at 2 days before sacrifice. With a single injection, E2-CDS did not affect serum luteinizing hormone (LH) levels at the 10 micrograms/kg dose but caused a dose-dependent reduction in serum LH of 39-52% at the dose range of 33 to 333 micrograms/kg. By contrast, multiple injections of E2-CDS caused a 32 to 76% reduction in serum LH levels at doses ranging from 10 micrograms/kg to 333 micrograms/kg. Additionally, multiple doses of E2-CDs caused a dose-dependent reduction in body weight at the 10 and 33 micrograms/kg doses with the higher doses causing no further weight reduction. For both single and multiple dosage groups, serum E2 levels remained unchanged after doses of E2-CDS of 10 and 33 micrograms/kg, then increased to 21 pg/ml for the single dosage group and to 23 pg/ml for the multiple dosage group at the 100 micrograms/kg dose, and to 59 pg/ml for singly-injected rats and 60 pg/ml for multiply-injected rats at the 333 micrograms/kg dose. Serum prolactin concentrations were closely correlated with serum E2 levels for both the single and multiple dose groups. These data reveal that a single or multiple doses of E2-CDS can reduce serum LH levels without elevating serum E2 or prolactin concentrations, supporting the concept of brain-enhanced delivery of estradiol with an estradiol chemical delivery system.

Adrenal Glands↗
PubMed1988

Chronic weight loss in lean and obese rats with a brain-enhanced chemical delivery system for estradiol.

Studies were undertaken to determine the effects on body weight and food intake of a chemical delivery system which preferentially delivers estradiol (E2) to the brain and there serves as a source for the sustained release of the steroid. We injected intravenously various doses of this estradiol-chemical delivery system (E2-CDS), E2-valerate (E2-VAL) or the dimethyl sulfoxide (DMSO) vehicle to young lean male rats and monitored body weight and 24 hr food intake for 39 days postinjection. E2-VAL caused a transient reduction in food intake and body weight gain. By contrast, a single injection of E2-CDS caused a chronic, dose-dependent reduction in the rate of body weight gain. In these lean rats, the duration of reduced body weight gain was not correlated with the observed transient reduction in food intake. In aged, obese male rats, E2-CDS caused a marked and chronic dose-dependent reduction in body weight. In contrast to lean rats, E2-CDS caused a long-term reduction in food intake in obese rats. To evaluate the importance of the E2-CDS-induced reduction in food intake in the observed persistent weight loss in obese rats, E2-CDS was administered to a group of obese rats and a second group which received the DMSO vehicle was pair-fed an equivalent amount of food daily. The resulting weight loss in both groups was equivalent. These results show that the enhanced delivery of E2 to the brain with the E2-CDS causes sustained reduction in the rate of body weight gain in lean rats and persistent weight loss in obese animals.

Animals↗
PubMed1988

Effects of a brain-enhanced chemical delivery system for estradiol on body weight and serum hormones in middle-aged male rats.

We have developed a redox-chemical delivery system for brain-enhanced drug delivery of estradiol based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Estradiol, when combined with the carrier, readily crosses the blood-brain barrier and upon oxidation of the carrier is "locked" in the brain. The aim of this study was to evaluate the effects of the estradiol-chemical delivery system (E2-CDS) on body weight change and associated alterations in the secretion of anterior pituitary hormones in middle-aged, male rats. The data revealed that rats receiving E2-CDS exhibited a significant weight loss by 2 days which continued to day 14, the last observation day. A significant weight difference was observed between E2-CDS and DMSO-treated animals. Serum estradiol levels of rats treated with E2-CDS were elevated 100-fold by day 1 and decreased thereafter and serum prolactin concentrations were doubled by 24 hours and continued to increase to the completion of the experiment. Testosterone levels were markedly suppressed by 24 hours while serum levels of LH, TSH, T3, T4 and GH were not significantly altered. These data indicate that the E2-CDS causes a long-term reduction in body weight and testosterone secretion and that these changes are not mediated by alterations in the secretion of anterior pituitary hormones.

Age Factors↗
PubMed1988

Hepatic regenerative enzyme activity after diffuse injury with galactosamine: relationship to histologic alterations.

Massive liver injury with 1000 mg/kg D-galactosamine was followed by a broad peak of thymidine kinase (TK) activity over 62 to 120 hours. The highest mean value was a 29-fold increase in activity. Three peaks of ornithine decarboxylase (ODC) activity were observed over the same time span. The first peak occurred at 45 hours, showing a sevenfold to eightfold increase in activity. Histologic evidence of necrosis peaked at 12 to 24 hours and was prominent over 54 hours. Periportal inflammation in response to the cellular injury was prominent from 12 to 96 hours and peaked at 45 to 62 hours. The curve of mitoses peaked at the same time as that of TK activity but was only 68% as extensive. The first peak of ODC activity occurred before there was any significant presence of mitoses or of TK activity. A smaller dose of 400 mg/kg resulted in a narrow peak of TK activity at 62 hours that was a 37-fold increase in activity. The total TK response was 43% of that seen after the larger dose, about in proportion to the dose given. The first ODC peak, representing the earliest evidence of regeneration, was earlier and more prominent after the 400 mg/kg dose. On the basis of areas under the curves, the amounts of necrosis and of periportal inflammation after 400 mg/kg were 36% of those seen after 1000 mg/kg. Corresponding figures for other response curves were 29% for mitoses, 33% for serum SGPT, and 71% for total ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1988

Brain-enhanced delivery of testosterone using a chemical delivery system complexed with 2-hydroxypropyl-beta-cyclodextrin.

Enhanced brain delivery of testosterone was suggested by application of a dihydropyridine in equilibrium pyridinium salt redox system. The drug delivery method is based upon the NAD+ in equilibrium NADH coenzyme system and utilizes the covalent attachment of testosterone to a dihydropyridine-type carrier. Upon administration of two such testosterone chemical delivery systems (T-CDS1 or T-CDS2), serum LH levels were suppressed by 71-87% after 24 hours and maintained through 5 days (28%) with T-CDS1. An equimolar dose of testosterone or testosterone propionate failed to suppress serum LH. Peripheral testosterone target tissues (seminal vesicles and prostate gland) were only slightly stimulated by T-CDS1. Complexation of T-CDS1 with 2-hydroxypropyl-beta-cyclodextrin allowed a lowering of the effective LH-suppressing dose of T-CDS1 from 25 mg/kg to 10 mg/kg, presumably by increasing the solubility of T-CDS1 in the blood. These findings suggest that testosterone can be effectively delivered to the central nervous system (CNS) with minimal peripheral effect, and the delivery of T-CDS1 to the CNS can be improved via complexation with 2-hydroxypropyl-beta-cyclodextrin.

Animals↗
PubMed1988

Hepatic failure toxins depress liver regenerative enzymes after periportal injury with allyl alcohol in the rat.

Hepatic regenerative enzyme (thymidine kinase and ornithine decarboxylase) activities were significantly depressed by subcoma doses of the hepatic failure toxins (NH4+, octanoic acid, and dimethyl disulfide) after selective injury with allyl alcohol. The inhibitory effect of NH4+ was greater than that of dimethyl disulfide, even though the neurologic effects of dimethyl disulfide were approximately comparable with those of the NH4+. There appeared to be a delay in the full expression of the depressive effects of octanoic acid and dimethyl disulfide. The resistance to these two toxins, particularly dimethyl disulfide, may reflect the resistance to injury of the oxidative processes prominent in periportal hepatocyte mitochondria. In comparison with pericentral injury or two-lobe hepatectomy, periportal injury seemed equally susceptible to regenerative enzyme inhibition by NH4+ but less susceptible to the effect of octanoic acid and dimethyl disulfide.

Ammonia↗
PubMed1987

Anxiolytic activity of a brain delivery system for GABA.

We evaluated the anxiolytic property of a brain-specific gamma-aminobutyric acid delivery system (GABA-CDS) in male rats by means of a drink-foot shock conflict procedure. Brain-specific delivery of the active compound was achieved by combination of GABA benzyl ester with an interconvertible dihydropyridine in equilibrium pyridinium salt carrier, which is "locked in" to the brain upon its oxidation. Pharmacokinetic studies revealed that the hydrophilic pyridinium salt form (G-Q+) of the GABA-CDS formed in situ remained in the brain for 12 h but was cleared from the blood and other peripheral tissues by 0.5-4 h. While the lipophilic form (G-DH) of the GABA-CDS caused a marked and sustained anxiolytic response when administered systemically, GABA and the charged pyridinium salt (G-Q+ form) of the GABA-CDS were ineffective. G-DH was injected at either 0, 4, 10 or 25 mg/kg IV in DMSO after rats were water and food deprived. After either 0.5, 2, 4, 8 or 24 h, rats were permitted 10 s of shock-free drinking of 10% sucrose, then given a 35 mA (DC) current through the drinking tube. Drinking time was recorded for 3 min. All doses of G-DH caused a significant increase in anxiolysis over control levels through 8 h. An increase (4 to 7-fold) in anxiolytic activity was observed through the 10 mg/kg dose with the 25 mg/kg dose causing no additional increase. No sedation or analgesia was observed at 2 h with any anxiolytic-producing dose of G-DH. These results suggest that G-DH elicits anxiolysis with minimal sedation, through the local brain action the G-Q+ or subsequent to the release of GABA.

Animals↗
PubMed1987

Evidence for the reestablishment of copulatory behavior in castrated male rats with a brain-enhanced estradiol-chemical delivery system.

We have developed a redox-chemical system for brain-enhanced drug delivery of estradiol based on an interconvertible dihydropyridine in equilibrium with pyridinium salt carrier. Estradiol, when combined with the carrier, readily crosses the blood-brain barrier and upon oxidation of the carrier is "locked" in the brain. The aim of this study was to evaluate the effects of an estradiol-chemical delivery system (E2-CDS) versus an equimolar dose of estradiol-17-valerate (E2-VAL) on copulatory behavior in orchidectomized rats. The data revealed that a single dose of E2-CDS was more efficacious than E2-VAL in stimulating mounting behavior (percent responding) and the effect was 100% through 5 weeks. E2-CDS increased intromission behavior more than E2-VAL through 28 days. Mount and intromission latencies were reduced by E2-CDS to a greater extent and for a longer time (28 days) than E2-VAL. Neither form of estradiol restored ejaculation parameters or penile reflexes. These data suggest that E2-CDS causes a potent and long-acting stimulation of proceptive and consummatory components of male sexual behavior, presumably acting through the local brain-release of estradiol.

Animals↗
PubMed1987

Action of food restriction on age-related changes in adipocyte lipolysis.

The effects of aging and of food restriction at different times during life on rat adipocyte responses to glucagon and epinephrine were explored by studying hormone-stimulated lipolysis, hormone binding, and phosphodiesterase activity. The times of food restriction were: (a) from 6 weeks of age, (b) limited to early life, and (c) beginning in young adult life. Hormone-sensitive lipolysis is lost with age. Food restriction from 6 weeks of age prevents this loss, and food restriction started in adult life causes the recovery of this lipolysis. Hormone binding studies reveal that: (a) changes in glucagon-stimulated lipolysis parallel changes in glucagon binding; (b) glucagon binding and glucagon-stimulated lipolysis correlate inversely with cell size; (c) changes in epinephrine-stimulated lipolysis are not due to changes in beta-adrenergic binding; and (d) neither beta-adrenergic binding nor epinephrine-promoted lipolysis correlate with fat cell size. Phosphodiesterase activity is not influenced by diet, making it unlikely to be a postreceptor component lost with age.

Adipose Tissue↗
PubMed1987

Serodiagnosis of postnatally and prenatally induced toxoplasmosis in sheep.

Nineteen pregnant (45 to 90 days of gestation) and 9 nonpregnant ewes were inoculated orally with 1,000 or 10,000 oocysts of Toxoplasma gondii. Pregnant ewes were euthanatized at days 14 (2 ewes), 21 (1 ewe), 23 (1 ewe), 28 (2 ewes), 35 to 42 (6 ewes), and 49 to 62 (6 ewes), and antibody titers in fetal and maternal sera were assayed, using the modified agglutination, latex agglutination, indirect hemagglutination, and dye tests. Although all ewes developed antibody titers of greater than or equal to 1,024 within 28 days after inoculation, fetuses were seronegative up to 28 days, using the modified agglutination test. Toxoplasma gondii antibodies were found in fetuses, using the modified agglutination and dye tests 35 days after ewes were inoculated. Latex agglutination and indirect hemagglutination tests were insensitive for detection of T gondii antibodies in ovine fetal sera. Toxoplasma gondii antibody titers in nonpregnant ewes were similar to those in pregnant ewes. Passively acquired T gondii antibodies from the colostrum decreased from 1,024 to less than 16 between 49 and 56 days of age in 1 lamb and between 62 and 106 days in its twin.

Animals↗
PubMed1986

Epidemiologic findings on a swine farm with enzootic toxoplasmosis.

A farm in Illinois had swine with enzootic Toxoplasma gondii infections. Ninety-five of 99 pigs had antibody against T gondii by the modified agglutination test; modified agglutination test titers were less than 1:10 (4 pigs), 1:10 (15 pigs), 1:20 (12 pigs), 1:40 (10 pigs), 1:80 (20 pigs), 1:160 (11 pigs), 1:320 (12 pigs), 1:640 (9 pigs), and greater than or equal to 1:1,280 (6 pigs). To trace the route of infection, Toxoplasma-free pigs were introduced into the farm and were evaluated serologically at various intervals. Analysis of data derived from these tracer pigs indicated that cannibalism was a major source of T gondii infection in the pigs.

Agglutination Tests↗
PubMed1986

Epizootiologic investigations on a sheep farm with Toxoplasma gondii-induced abortions.

During the lambing season of 1983/1984, 8 of 44 purebred Hampshire ewes on a farm in Knoxville, Md had reproductive problems. In at least 4 of these ewes, the problem was attributed to toxoplasmosis. Necrosis and Toxoplasma gondii tachyzoites were found in placental specimens from 3 ewes. Agglutinating antibody to T gondii, at a titer of 1:80, was found in pleural fluids of both fetuses aborted from 1 ewe; this ewe had an antibody titer of 1:6,400 at the time of abortion. In another ewe, the diagnosis was confirmed by the isolation of T gondii from the placenta and 1 of her lambs. Of numerous free-roaming adult cats on the farm, 16 were trapped, euthanatized, and examined for T gondii. Agglutination antibody to T gondii, at titers of 1:4 to 1:64, was found in serum samples from all the cats. Toxoplasma gondii was isolated from the brain and skeletal muscles of 9 of the cats, and from the feces of 1 cat. Blood samples obtained from all 78 sheep on the farm 6 months after the episode of abortion were examined for antibody to T gondii. Agglutinating antibody titers to T gondii were less than 1:16 in 46 sheep, 1:16 in 16, 1:64 in 12, 1:256 in 2, 1:024 in 1, and 1:4,096 in 1. Analyses of serologic data in sheep of various age groups suggested that the Toxoplasma infection was acquired sporadically, probably from feed contaminated with oocysts.

Abortion, Veterinary↗
PubMed1986

Toxoplasma gondii-induced abortion in dairy goats.

Three of 8 goats on a Maryland farm aborted or had dystocia associated with toxoplasmosis during the winter of 1984. Doe 1 aborted a decomposed fetus 30 days before term. Modified agglutination test (MAT) antibody titers against Toxoplasma gondii were found in pleural fluid of the fetus (1:1,024) and in serum of doe (1:4,096 at 31 days after abortion). Doe 2 aborted a fetus 5 days before term; MAT antibody was found in the pleural fluid of the fetus (1:16,384) and in the doe's serum (1:4,096 on the day of abortion). Placenta from both does had foci of necrosis characteristic of toxoplasmosis, and T gondii was identified in lesions. Doe 3 had dystocia 7 days before term and a partially decomposed fetus was delivered by cesarian section; MAT was found in pleural fluid of the fetus (1:1,024) and in serum from the doe (1:4,096 on the day of abortion). Focal gliosis and calcification were seen in brain specimens from 2 of the 3 fetuses. None of the does produced milk after abortion. Two other does (No. 4 and 5) delivered apparently healthy kids transplacentally infected with T gondii; MAT in serum of both does was 1:4,096. Doe 4 delivered 3 kids; MAT titer in a serum from each kid 38 days after birth was 1:16,384. Doe 5 delivered 1 kid with a serum MAT titer of 1:1,024 at 38 days after birth. The 3 remaining does had MAT titers of 1:256, 1:16, and 1:16, and all delivered healthy kids. Epizootiologic evidence suggested that the does acquired T gondii infection from oocysts passed in feces of domestic cats on the farm. The MAT titers of 4 cats on the farm were 1:65,356; 1:1,024; 1:16; and 1:1,024.

Abortion, Veterinary↗
PubMed1986

Hepatic regenerative enzyme activity after pericentral and periportal lobular toxic injury.

Pericentral and periportal liver injuries involving less than 50% of the parenchyma were produced with acetaminophen and allyl alcohol, respectively. Doses were selected to produce comparable peak serum malate dehydrogenase, sorbitol dehydrogenase, and SGPT activities. The regenerative response was assessed by serial measurements of hepatic thymidine kinase (TK) activity and ornithine decarboxylase (ODC) activity. The initial responses reflected in ODC activity were more or less similar. However, the ultimate regenerative response reflected by TK activity was almost three times as great after periportal injury as after pericentral injury, after allowing for differences in the extent of necrosis. Histologic examination also showed greater mitotic and tissue reparative responses after periportal injury. These results suggest that the concept of hepatocellular heterogeneity applies to the regenerative response of liver cells as well as the metabolic functions previously identified.

Acetaminophen↗
PubMed1986

Hepatic iron overload in renal transplant recipients: ultrastructural observations.

This study describes the ultrastructural features of hemosiderosis occurring in five transplant recipients. Iron deposits in the form of homogeneous and heterogeneous siderosomes (iron-laden lysosomes) were found within the hepatocytes and macrophages in areas of fibrosis, and to a lesser degree within Kupffer cells and bile duct epithelium. Disruption of siderosomal membranes with extrusion of ferritin particles into the cytosol was demonstrated in these specimens and may be significant in the pathogenesis of hepatocellular injury.

Adult↗
PubMed1986

Field evaluation of the enzyme-linked immunosorbent assay for swine trichinosis: efficacy of the excretory-secretory antigen.

A field evaluation of an enzyme-linked immunosorbent assay (ELISA) for swine trichinosis was done with sera obtained from 5 herds experiencing ongoing transmission of Trichinella spiralis. Epizootiologic studies conducted on these herds offered an opportunity to evaluate the accuracy of an ELISA, using larval T spiralis excretory-secretory antigens. Sera from 162 infected pigs and 143 serum samples from noninfected pigs originating from the same farms were tested. The infection status of the pigs was determined by digestion of diaphragm or tongue muscle samples. Two criteria were established to classify the ELISA optical density (OD) readings: Criterion I stated that an OD greater than or equal to 5 times the mean OD of several normal swine sera pools was positive; criterion II stated that a OD greater than or equal to 4 times the normal sera values was positive. The results obtained did not reveal obvious serologic variations among infected herds located in the 4 states involved. Overall, the test detected 93% (criterion I) and 96% (criterion II) of infected pigs. The majority of false-negative sera was from hogs that had less than 5 larvae/g of muscle; 1 hog had 73.8 larvae/g of diaphragm muscle. The false-positive rates were 8% for criterion I and 9% for criterion II. The actual rate for these false-positive samples may have been overestimated, because generally, only small tissue samples (0.4 to 10 g) were digested; larger sample sizes might have altered the results. The relevance of this qualification is that these pigs originated from herds with prevalence rates greater than 50%. Other factors that may account for occasional false-positive sera or false-negative sera in the swine trichinosis ELISA are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Changing trends in the surgical treatment of invasive carcinoma of the vulva.

Twenty-nine years experience with 346 patients with invasive carcinoma of the vulva is presented. More than 90 per cent had squamous carcinoma. The primary mode of treatment was surgical. Two hundred and ninety-six patients were treated primarily with surgical treatment, 120 underwent radical vulvectomy and bilateral groin and pelvic lymphadenectomy, 133 had radical vulvectomy with bilateral groin dissection and 390 receiving nonradical procedures. Thirteen patients had radical operations plus pelvic exenteration for advanced disease. There were no intraoperative deaths, but 16 (5.4 per cent) died within 28 days of the operation. The uncorrected over-all five year survival rate was 66 per cent. In the presence of negative nodes, it was 83 per cent and with positive nodes, it was 38 per cent. Fifty per cent of those treated with exenteration are alive and disease-free at five years or more. Since one-third of the patients presented with advanced disease (Stages III and IV), earlier diagnosis and prompt referral must be encouraged to improve surgical results.

Adult↗