Influence of dithiocarb on the biliary excretion of paracetamol and bilirubin in rats

Summary In bile-fistula rats, the biliary elimination of conjugated paracetamol and conjugated bilirubin is diminished by simultaneous administration of dithiocarb. This dithiocarb effect could be the result of the interference with the glucuronidation of the compounds.     

Effect of ethanol on levels of isoniazid, sulfanilamide and sulfapyridin in mouse blood.

The effect of ethanol of blood levels of free and conjugated sulfonamides (sulfanilamide and sulfapyridin) and isoniazid was investigated in mice. Ethanol (1.5 and 4 mg/g i.v.) enhanced the amount of conjugated isoniazid without affecting the total amount of isoniazid in blood, and tended to raise the total amount of the sulfonamides.     

Effect of ethanol on levels of isoniazid,sulfanilamide and sulfapyridin in mouse blood

Summary The effect of ethanol on blood levels of free and conjugated sulfonamides (sulfanilamide and sulfapyridin) and isoniazid was investigated in mice. Ethanol (1.5 and 4 mg/g i.v.) enhanced the amount of conjugated isoniazid without affecting the total amount of isoniazid in blood, and tended to raise the total amount of the sulfonamides.Acknowledgment. The author is indebted to Mrs S. Schütze for excellent technical assistance.     

共轭单圈图的广义Randic指标的最小值

图G的广义Randic指标定义为Rα(G)=∑(dudv)α,其中α为任意实数,du为顶点u的度.本文使用反证法,通过分uu∈E(G)类讨论,研究了α=-1时,共轭单圈图的广义Randic指标的最小值问题,给出了最小值及相应的结构.     

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.     

Evidence for the induction and release of pancreatic folylpolyglutamate hydrolase by the ingestion of folyl polyglutamates in the rat

Pteroyl polyglutamate hydrolase (folyl conjugase), which hydrolyses the dietary polyglutamyl folates into simple forms prior to absorption, has been shown to be induced in rat pancreas in response to dietary polyglutamyl folates but not by ingestion of synthetic unconjugated folates. Folate absorption, as measured by the rise in serum folate levels after ingestion, of dietary conjugated folates is impaired in pancreatectomised animals whereas absorption of synthetic simple folate is not. A severe build-up of folyl conjugase is observed in the lumen of control but not in pancreatectomised animals after dietary folate ingestion. These results taken together would suggest that dietary folates are hydrolysed to monoglutamyl forms suitable for absorption in the lumen; the hydrolysis is catalysed by a luminal folyl conjugase of pancreatic origin induced by dietary conjugated folates.     

Evidence for the induction and release of pancreatic folylpolyglutamate hydrolase by the ingestion of folyl polyglutamates in the rat.

Pteroyl polyglutamate hydrolase (folyl conjugase), which hydrolyses the dietary polyglutamyl folates into simple forms prior to absorption, has been shown to be induced in rat pancreas in response to dietary polyglutamyl folates but not by ingestion of synthetic unconjugated folates. Folate absorption, as measured by the rise in serum folate levels after ingestion, of dietary conjugated folates is impaired in pancreatectomised animals whereas absorption of synthetic simple folate is not. A severe build-up of folyl conjugase is observed in the lumen of control but not in pancreatectomised animals after dietary folate ingestion. These results taken together would suggest that dietary folates are hydrolysed to monoglutamyl forms suitable for absorption in the lumen; the hydrolysis is catalysed by a luminal folyl conjugase of pancreatic origin induced by dietary conjugated folates.     

Seasonal variation in plasma testosterone in a teleost fish]

The plasma free testosterone levels show distinct variations related to the seasonal testicular cycle. The conjugated testosterone presents correlative but not strictly parallel changes.     

Acid phosphatase activity of cytolytic T cells during cytolysis].

The localization of Golgi areas, particularly lysosomal bodies detected by their acid phosphatase activities, has been determined in the cytotoxic lymphocytes conjugated to their target cell. The study points out the preferential situation of these organelles close to the contact area between the two cells during the target cell lysis.     

Ultrastructural identification of human tonsil T-lymphocytes by peroxidase-conjugated anti-HTLA serum.

A horse anti-serum rendered specific for human T-lymphocytes was conjugated with peroxidase and used for ultrastructural identification of human tonsil T-lymphocytes. With T- and B-enriched suspensions, virtually all T-lymphocytes were labelled with Po-anti-HTLA, whereas no B-cells were stained with this conjugate. The labelling HTLA conjugate confirm the ultrastructural characteristics of thymus-dependant cells.     

Effect of glucose administration on bilirubin excretion in the rabbit

The effect of i.v. infusion of glucose on the hepatic handling of bilirubin was examined in rabbits. A significant increase in the excretion of conjugated bilirubin into the bile was observed, accompanied by a decrease in bilirubinemia. Hepatic bilirubin concentrations were lowered and the UDP-glucose concentrations and liver UDP-glucuronosyl and UDP-glucosyl transferase activities increased.     

Effect of glucose administration on bilirubin excretion in the rabbit

Summary The effect of i.v. infusion of glucose on the hepatic handling of bilirubin was examined in rabbits. A significant increase in the excretion of conjugated bilirubin into the bile was observed, accompanied by a decrease in bilirubinemia. Hepatic bilirubin concentrations were lowered and the UDP-glucose concentrations and liver UDP-glucuronosyl and UDP-glucosyl transferase activities increased.     

Flavomycoin,ein neues antifungales Polyenantibiotikum

Summary A new antifungal polyene antibiotic flavomycoine is described. By structural investigations it was shown that this antibiotic belongs to a new type of polyene antibiotics in which the pentaene chromophore is conjugated to the lactone carbonyl group.     

Immunocytochemical labeling of human chromosomes by antibodies from human autoimmune serum]

Mitotic human chromosomes are successively irradiated by ultraviolet, incubated with serum from a patient showing systemic lupus erythematosus (S.L.E.), and antihuman Sheep serum conjugated with peroxidase. After revelation by diaminobenzidine (DAB) banding patterns are pointed out. The chromosome labelling is discussed in comparison with results obtained in other immunocytochemical experiments.     

Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery

Delivery of macromolecules into living cells by arginine-rich cell penetrating peptides (AR-CPPs) is an important new avenue for the development of novel therapeutic strategies. However, to date the mechanism of this delivery remains elusive. Recent data implicate endocytosis in the internalization of AR-CPPs and their macromolecular cargo and also indicate limited delivery of macromolecules into the cell cytoplasm and nucleus. Different types of endocytosis – clathrin-dependent endocytosis, raft/caveolin-dependent endocytosis and macropinocytosis – are all implicated in the uptake of AR-CPPs and their cargo into different cells. Cationic AR-CPPs dramatically increase uptake of conjugated molecules through efficient binding to surface proteoglycans. Whether this increase in binding can assure delivery of a sufficient amount of functionally active macromolecules into the cytoplasm and nucleus or whether there is a specific mechanism by which AR-CPPs facilitate the escape of conjugated cargo from endosomes remains to be understood. Received 30 June 2005; received after revision 9 August 2005; accepted 30 August 2005     

A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.     

Metabolism of endosulfan in the Indian honey bee

Summary Metabolism of topical endosulfan in the Indian honey bee,Apis cerana indica F., was studied. The two endosulfan isomers were found to be interconvertible in bees. The products of metabolism were endosulfan sulfate, diol, ether, hydroxyether, lactone and two unknown compounds. Endosulfan diol, hydroxyether and lactone were found to be conjugated in excreta of the treated bees.Acknowledgment. Authors are grateful to the department of Horticulture and Food Technology for providing gas chromatography facilities.     

Cholera toxin B-subunit incorporation into synaptic vesicles of the neuromuscular junction of the rat

The B-subunit of cholera toxin, a nontoxic macromolecule which binds specifically to GM1 ganglioside, was conjugated to colloidal gold and injected into skeletal muscle of the rat. It was taken up rapidly in vesicles in the terminal axons at the neuromuscular junctions. Injection of albumin-colloidal gold conjugates resulted in an insignificant uptake. The results indicate that uptake of extracellular macromolecules into the terminal axon of the neuromuscular junction may be greatly enhanced by binding to gangliosides at the presynaptic membrane, and that it may occur without association with vesicular recycling related to transmitter release.     

The effect of bile salts on thyroxine 5′-monodeiodination in rat liver homogenate

Summary Unconjugated and conjugated bile salts inhibited the conversion of thyroxine to 3,3,5 triiodothyronine in rat liver homogenate.This work was supported in part by a grant from the Imanaga Foundation, Nagoya, Japan.     

Hsp70: a carrier molecule with built-in adjuvanticity

One problem associated with the development of subunit vaccines is their limited immunogenicity, due to their physico-chemical structure, their inability to encounter the correct MHC restriction element, or the need for strong adjuvants to be delivered along with them. These problems are usually solved by conjugating target epitopes (peptides or oligosaccharides) with carrier proteins which provide a source of T-cell epitopes recognised by a large proportion of the vaccinated individuals. We have shown that mycobacterial hsp65 and hsp70 exert a strong helper effect in vivo when conjugated to synthetic peptides or oligosaccharides. Interestingly, this helper effect did not require the need for any adjuvant, either in mice or in monkeys. The helper effect mediated by the hsp65 required that animals were previously primed with either live BCG or the hsp65 alone; on the other hand, such a priming was not required when the hsp70 was used in the conjugates. Similar results were obtained with HSP molecules fromEscherichia coli. This may suggest that the adjuvant-free helper effect observed applies not only to mycobacterial HSP, but also to HSP from other prokaryotes. These findings suggest that microbial hsp70 could be considered for the design of conjugated vaccine constructs for eventual human use.