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Primary isolation of the bovine spongiform encephalopathy agent in mice: agent definition based on a review of 150 transmissions.

In the epizootic of bovine spongiform encephalopathy (BSE) in Great Britain, the cattle in which a positive diagnosis was made numbered almost 180 000, but strain characterization was performed on only a very small sample of these cases. This report describes the results of BSE transmission to Prnp(a) mice from 150 transmission experiments at the Veterinary Laboratories Agency (VLA) over the last decade. These data, derived from a large sample of BSE-affected cattle, confirmed previous reports that show no evidence for diversity in BSE isolates. The agent was readily transmitted to mice, with a mean incubation period of 408 days in the RIII strain. Because the incubation period was related to the titre of the inoculum, it is not a reliable characteristic of strain type on primary isolation. Consistent neuropathological changes associated with infection by the BSE agent in RIII and C57Bl mice included focal vacuolation in the dorsal cochlear nuclei, vacuolation of the granule cell layer of the cerebellum, absence of lesions in the hippocampus and in the molecular layer of the cerebellum, and a fine particulate distribution of disease-specific PrP (demonstrated immunohistochemically), with few or no amyloid plaques. These features, together with the conventional lesion profile, will be of use in distinguishing the agents of BSE and scrapie in sheep.

Animals↗

Effect of natriuretic agents, vasoactive agents and of the inhibition of metabolism on sodium handling in the isolated perfused kidney of the nephrotic rat.

1. The kidney taken from a rat rendered nephrotic by exposure to puromycin aminonucleoside retains sodium abnormally when perfused in isolation and has an abnormally low vascular resistance (J. D. Firth et al., Clin. Sci. 1989; 76, 387-95). In this study the relation of oxygen consumption to sodium reabsorption has been examined in the isolated nephrotic organ, which has also been exposed to a variety of natriuretic agents and to the effect of inhibition of metabolism by cooling, in an attempt to discern the transport process, or processes, responsible for abnormal tubular handling of sodium. In addition, the effects of three endogenous vasoconstrictors, noradrenaline, angiotensin II and endothelin, on the function of the isolated nephrotic kidney have been examined. 2. The ratio of mol of sodium reabsorbed by the tubules of the isolated nephrotic kidney to mol of oxygen consumed was reduced in comparison with the control kidney (means +/- SEM): 9.22 +/- 0.97 versus 15.43 +/- 1.55 (P less than 0.002). 3. In the presence of ouabain (1 mmol/l), acetazolamide (1 mmol/l), frusemide (200 mumol/l), the combination of these three agents together, hydroflumethiazide (100 mumol/l), benzamil (100 nmol/l) or atrial natriuretic peptide (1000 pmol/l), a lesser increment in sodium excretion was induced in the isolated nephrotic kidney than in the control kidney and the nephrotic organ continued to excrete less sodium in both absolute and fractional terms. 4. This suggests that enhanced tubular sodium reabsorption in the isolated nephrotic kidney does not depend upon abnormally increased activity of the Na+/K(+)-adenosine triphosphatase, bicarbonate-dependent sodium transport, Na+/K+/2Cl- co-transport, electrically neutral proportionate reabsorption of sodium and chloride (distal tubule), epithelial sodium channel (distal tubule) or atrial natriuretic peptide-sensitive sodium transport processes. 5. When isolated nephrotic kidneys and normal kidneys were cooled to 8-10 degrees C the handling of sodium became virtually identical in the two groups. On re-warming to 37 degrees C, the original differences in sodium handling between nephrotic and control kidneys were restored. This implies that the mechanism responsible for the abnormal tendency to retain sodium is temperature-sensitive; as yet it remains otherwise undefined. 6. The sensitivity of the renal vessels to noradrenaline, angiotension II and endothelin, as judged by the percentage reduction in perfusate flow rate produced by a given concentration of any of these agents, was not substantially altered in the nephrotic kidney compared with the control kidney. Increase in vascular tone was not associated with amelioration of the tendency of the isolated nephrotic organ to retain sodium. Increasing concentrations of angiotensin II caused the filtration rate to increase in the nephrotic kidney. This effect was unexpected: in the control preparation, as anticipated, angiotensin II caused the filtration rate to decrease.

Acetazolamide↗

Population regulation of a classical biological control agent: larval density dependence in Neochetina eichhorniae (Coleoptera: Curculionidae), a biological control agent of water hyacinth Eichhornia crassipes.

The release of classical biological control agents has reduced the economic, environmental and social problems caused by water hyacinth, Eichhornia crassipes; however, additional control measures are needed in some locations. Water hyacinth plants were treated with different densities of eggs of the weevil Neochetina eichhorniae Warner, one of the main control agents, under different nutrient regimes in a controlled experiment. Plants were destructively sampled and the development of N. eichhorniae was assessed. The survival of first and second instars declined as larval density increased. Plant nutrient status did not directly affect the mortality rate of larvae, but at higher nutrient concentrations larvae developed faster and were larger at a given developmental stage. It is argued that the density dependence operating in N. eichhorniae occurs through an interaction between young larvae and leaf longevity. Consequently, events which disrupt water hyacinth leaf dynamics, e.g. frost or foliar herbicides, will have a disproportionately large effect on the control agents and may reduce the level of control of the host.

Animal Nutritional Physiological Phenomena↗

Studies on the agent of infectious hepatitis; propagation of the agent in tissue culture and in the embryonated hen's egg.

Two viral agents have been procured from patients with infectious hepatitisin two widely separated outbreaks of the disease by transfer of acute stage serum and stool filtrates to and passage in tissue cultures of rabbit liver cells in roller tubes and minced chick embryos in Simms-Sanders medium followed by passage in the amniotic cavity of the chick. Cultures of both agents, designated the Akiba and NL strains of virus, induced mild hepatitis without jaundice in the majority of volunteers tested after an incubation period of from 9 to 38 days. Although these agents have not been identified definitely as the virus of infectious hepatitis, the available evidence, as discussed, is compatible with the suggestion that such they are.

Animals↗

Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture.

A previous paper (Kimberlin & Walker, 1977) described an experimental model of scrapie in hamsters in which the incubation period decreased progressively over the first 4 passages before becoming stable at the 5th and subsequent passes. Studies have been made of some of the agent strains present in brains taken from the 2nd, 3rd, 4th and 6th hamster passes. The results indicate the presence of at least two strains of agent at the 3rd passage level. One of these (431K) is highly pathogenic for mice and the other (263K) has an extremely low pathogenicity for mice. However only one of these strains (263K) is present in hamster brain after the 6th serial passage. It is suggested that the 'adaptation' of scrapie to hamsters may involve the selection, from a mixture, of a single strain which is highly pathogenic for hamsters. The possibility of modification of the properties of agent strains on passage discussed.

Animals↗

Contrast agent nephrotoxicity: comparison of ionic and nonionic contrast agents.

The effects on glomerular and proximal tubular function of an ionic contrast agent (sodium meglumine diatrizoate) and a nonionic agent (iopamidol) were compared in 34 patients with normal renal function. The patients received large doses (2.5 ml/kg body weight) of contrast material for IV digital subtraction angiography. Urine samples, collected before, immediately after, and on the first and third days after digital subtraction angiography, were analyzed for albumin, alanil-aminopeptidase, alpha-glucosidase, and beta-2-microglobulin. The changes noted were mild and of short duration with both contrast agents, despite the high dose given. These results suggest that, at least as far as renal toxicity is measured by these tests is concerned, ionic monomers can be safely used instead of more expensive nonionic media in procedures, such as digital subtraction angiography, that require high doses of contrast material.

Adult↗

The insulin-mimetic agent vanadate promotes receptor endocytosis and inhibits intracellular ligand-receptor degradation by a mechanism distinct from the lysosomotropic agents.

Vanadate (sodium orthovanadate) is an insulin-mimetic agent and phosphotyrosine phosphatase inhibitor that has been proposed as a potential therapeutic agent for diabetes. We previously reported that vanadate decreased the number of cell-surface insulin receptors but inhibited receptor degradation in cultured lymphocytes (IM-9) (1). To determine whether vanadate affected receptors without intrinsic tyrosine kinase activity, its effects on LDL and transferrin receptors and their ligands were examined. Vanadate exposure resulted in a dose- and time-dependent decrease in LDL binding to cultured human fibroblasts associated with a decrease in cell surface receptor number while total solubilized cell LDL receptors increased. Vanadate also inhibited the LDL-mediated downregulation of total cellular LDL receptors in the absence and presence of cycloheximide consistent with an inhibition of LDL receptor degradation. In the case of the ligand, vanadate augmented the accumulation of intact 125I-LDL associated with an inhibition of up to 80% of the ability of LDL to decrease cholesterol synthesis. Since these actions were similar to the effects of lysosomotropic agents, we examined the effect of vanadate on intraendosomal pH using the fluorescent probe acridine orange. In contrast with chloroquine and NH4Cl, vanadate did not neutralize the pH of the acidic intracellular compartment. Furthermore, after a transient insulin-like effect, chronic exposure to vanadate diminished 125I-diferric transferrin binding to rat adipocytes. In contrast with the inhibitory action of NH4Cl, intracellular 59Fe uptake remained unaffected and was proportional to cell-surface binding capacity in the presence of vanadate. These data demonstrate a chronic effect of vanadate to promote the accumulation of intracellular receptors and to inhibit ligand and receptor degradation. The latter effect is not mediated by pH changes, appears to be localized to a late endosomal/lysosomal compartment, and suggests a possible role for tyrosine dephosphorylation in the regulation of receptor-ligand degradation.

Adipocytes↗

Adhesiveness of glass ionomer cement containing tannin-fluoride preparation (HY agent) to dentin--an evaluation of adding various ratios of HY agent and combination with application diammine silver fluoride.

We bonded a glass ionomer cement (GIC) containing various amounts of incorporated tannin-fluoride preparation (HY agent) to bovine dentin and investigated the effect of the ratio of incorporated preparations and the changes in bond strength over time. HY agent was incorporated into the powder at 0% (HY0), 1.5% (HY1.5), 5.0% (HY5), and 10.0% (HY10) by weight. The shear bond strength and percent of the cohesive failure were measured. Similar tests were performed on samples where diammine silver fluoride was applied to the dentin prior to placing the cement. It was found that the bond strength on the first day was increased by incorporating 1.5% of the HY agent in the GIC. The combined use of diammine silver fluoride increased the bond strength of the GIC.

Adhesiveness↗

[Prophylaxis of recurrence in superficial bladder carcinoma by intravesical chemotherapy--comparative study between instillation of combined double anticancer agents and single anticancer agent].

We performed a study to compare the usefulness of double or single anticancer agents in the prophylactic treatment after the transurethral resection (TUR) of superficial bladder cancer. We experienced 127 superficial bladder cancer cases. Of these cases, 42 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 56 with ADR, PEP, epirubicin (epi-ADR) or pirarubicin (THP) only, and the remaining 29 with TUR only. Nonrecurrence rates were significantly higher in the intravesical treated cases than in the cases with TUR only, and also significantly higher in the cases treated with ADR and PEP than the other treated cases. We concluded that intravesical chemotherapy with combined agents was more effective than with a single agent.

Administration, Intravesical↗

Positive and negative oral contrast agents for combined abdominal and pelvic helical CT: first iodinated agent and second water.

Combined abdominal and pelvic helical computed tomography (CT) with intravenous contrast media was performed on 19 patients with 400 mL of diluted iodine solution 60 minutes before and 400 mL of water just before CT. The distal small bowel was opacified by the positive contrast agent, and the stomach by the negative contrast agent in all patients. The gastric contents were homogenous, and the density was a mean +/- standard deviation 2.5+/-7.3 HU. The difference between the densities of the gastric contents and of the gastric wall (mean +/- s.d. 80.8+/-20.9 HU) was statistically significant (p<.05). There were no pseudotumors. Thus our protocol, first diluted iodine solution and second water, can be used as a method for the oral administration of contrast agents for combined abdominal and pelvic helical CT with intravenous contrast media.

Administration, Oral↗

Ventilation agents--what agents are currently used?

A survey of radiologists and nuclear physicians in 360 hospitals in the UK was undertaken to assess the current use of pulmonary ventilation agents. Replies were received from 340 (94%) hospitals. Of these, 200 (59%) provided lung scanning. The agents used for ventilation studies were Tc-labelled aerosols (118, 59%), 81Krm (58, 29%), 133Xe (42, 21%) and 127Xe (4, 2%). Nine (4.5%) hospitals performed perfusion scintigraphy without providing ventilation imaging. Thirty-two (16%) hospitals used more than one agent for ventilation imaging.

Humans↗

[Adhesive efficiency of new bonding agents to dentin on bonding agent using urethane acrylate oligomer].

The tensile bond strength of new bonding agents on human dentin treated with 37% phosphoric acid solution for 60 sec to a photocurable composite resin was measured and the fractured surface was then observed by SEM. The new bonding agents consisted of various 20 wt% high molecular monomers (MW. 1500, 5000, urethane acrylate oligomer) as a base monomer. The best bonding agent was a mixture of 20 wt% 1500 molecular monomer as a base monomer and the value of the tensile bond strength was 91 +/- 17 kgf/cm2. The tensile bond test and SEM image of the fracture surface suggested that a high molecular monomer as a base monomer promoted the adhesive efficiency to human dentin.

Acrylic Resins↗

Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery.

In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented.

Adrenergic alpha-Agonists↗

Resistance to reinfection with a chlamydial agent (guinea pig inclusion conjunctivitis agent).

Although most chlamydial infections are chronic or recurrent, infection of the guinea pig's eye with guinea pig inclusion conjunctivitis (GPIC) agent induces a marked resistance to reinfection. To characterize this resistance to GPIC agent, we compared the disease and infection in previously infected guinea pigs with that in animals infected for the first time. In animals experiencing primary infection, even the lowest dose (10 egg-lethal doses [ELD50]) produced the disease and chlamydial inclusions in conjunctival smears, but the incubation period became progressively shorter with the highest inocula (10(4) and 10(5) ELD50). In animals with previous infection only these two highest inocula produced disease and infection, but the disease was short-lived, and replication of the agent was severely limited. The mechanism of this resistance may be due to secretory antibody in the tears, cellular immunity, or other local factors.

Animals↗

A "de-streaking" method for two-dimensional electrophoresis using the reducing agent tris(2-carboxyethyl)-phosphine hydrochloride and alkylating agent vinylpyridine.

Optimal isoelectric focusing in the alkaline region remains a challenge in two-dimensional gel electrophoresis (2-DE), though various attempts had been made to reduce basic end streaking. The present study reports the application of a novel reduction and alkylation step prior to 2-DE analysis using tris(2-carboxyethyl)-phosphine hydrochloride as a reducing agent and vinylpyridine as an alkylating agent. This simple sample preparation approach effectively eliminates basic end streaks, thereby enabling the analysis and identification of more protein spots resolved by 2-DE.

Alkylating Agents↗

[Skin tanning and light protection-theory, agents and analytic aspects. 1. Skin tanning and skin tanning agents].

The different approaches to achieving skin tanning with emphasis on natural tanning, due to UV radiation of the sun or solaria, and artificial tanning through tannings agents are described. In contrast to the artificial tan the natural tan is a protection against UV radiation and is caused by pigmentation (melanin formation). The artificial tanning is based on a chemical reaction usually by means of dihydroxy acetone (melanoidin formation). Reaction mechanisms by both agents are reported. The determination of dihydroxy acetone in cosmetic tanning preparations by TLC, GC, HPLC, enzymatic tests and by a new method for capillary GC including sample preparation is described. When exceeding the natural protection mechanisms the skin should be protected by physico-chemical measures. The active principles in sunscreens are the UV filtering substances. UV filters permitted in the EG are listed. 2-Hydroxy benzophenone is used as an example to explain the mechanism of UV filtering substances. Analysis of UV filtering substances in cosmetic sunscreens by TLC, GC, HPLC is described as well as a fast and simple method for separation of lipophilic UV filters followed by capillary GC determination.

Chromatography, Gas↗

The interaction of the cardioprotective agent ICRF-187 [+)-1,2-bis(3,5-dioxopiperazinyl-1-yL)propane); its hydrolysis product (ICRF-198); and other chelating agents with the Fe(III) and Cu(II) complexes of adriamycin.

Membrane-permeable ICRF-187 [+]-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane) has shown promise as a cardioprotective agent against adriamycin-induced cardiotoxicity. ICRF-187 may act through its rings-opened hydrolysis product (ICRF-198), which has an EDTA-type structure and, likewise, strongly binds metal ions. The reactions of these compounds with Fe3+-adriamycin and Cu2+-adriamycin complexes were examined. ICRF-198 quickly and completely removed both Fe3+ and Cu2+ from their complexes with adriamycin. ICRF-187 also reacted directly, but more slowly, with Fe3+-adriamycin to remove Fe3+ from the complex. This reaction was first order in ICRF-187 and Fe3+-adriamycin and yielded a second order rate constant of 123 M-1 min-1. Metal ion-complex promoted hydrolysis may thus contribute to the in vivo hydrolysis of ICRF-187 to its metal ion-chelating active rings-opened form. Both ICRF-187 and ICRF-198 were very effective in preventing the Fe3+-adriamycin induced inactivation of the cytochrome c oxidase activity of submitochondrial particles. A number of other chelating agents (desferal; penicillamine; DTPA; EDTA; TPEN; bathophenanthroline sulfonic acid; 2,2'-bipyridine; 1.10-phenanthroline, glutathione and 2-mercaptoethanol) were also examined for their ability to remove Fe3+ and Cu2+ from their complexes with adriamycin.

Cardiotonic Agents↗

Enhancement by electron-affinic agents of the therapeutic effects of cytotoxic agents against the KHT tumor: structure-activity relationships.

We have studied the effectiveness of various electron-affinic and other modifying agents on the in vivo response of the KHT sarcoma to various cytotoxic agents. Misonidazole (MISO) showed good enhancement with CCNU, methyl-CCNU, BCNU and chlorambucil (CHL), a small enhancement with cyclophosphamide (CYC), but none with melphalan or HN2. With CYC a further small enhancement was obtained with a multiple-dose pretreatment, but host toxicity was also increased. Lipophilicity was more important than electron-affinity for CCNU enhancement. Several lipophilic analogues (e.g. benznidazole and Ro 07-1902) gave enhancements superior to MISO, whereas hydrophilic analogues were inferior. Similar results were obtained with CHL. Enhancement of CCNU response was seen with the nitrofuran, nitrofurantoin, and the quinone, anthraquinone sulphonate. The non-electron affinic compound imidazole gave enhancement with CHI, but not with CCNU. The inhibitor of drug-metabolizing enzymes SKF 525A gave excellent enhancement with both CHL and CCNU.

Animals↗