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At least 811 records · Page 45Linked to original sources

PubMed1990

Tissue distribution of angiotensin converting enzyme and its inhibition by perindopril in pregnant rabbit and fetus.

The role of the renin angiotensin system (RAS) during pregnancy is not fully understood but numerous studies point to its importance in the homoeostasis of the fetal blood pressure and in the physiology of the fetal kidney near term. The aim of this study was to investigate the tissue distribution of angiotensin-converting enzyme (ACE) in the pregnant rabbit and its fetus and to assess the effect of Perindopril (PIL) a new ACE inhibitor on maternal and fetal tissue ACE activity. On day 28 of gestation, animals of the experimental groups were gavage-fed with 1 mg PIL or 10 mg PIL. ACE activity was assayed in tissue homogenates and serum with a radio-enzymatic method using (Gly-1-14C)-hippuryl-L-histidyl-leucine as specific substrate. In the kidney of control pregnant rabbit, decreasing values of ACE were found with a concentration gradient from the cortex to the inner papilla. ACE values in lung were comparable to those seen in kidney cortex. A significant effect of PIL was found with a percentage of inhibition of ACE activity in the renal cortex above 74% after 1 mg PIL and 88% after 10 mg PIL. In the control group, ACE activity was predominant in lung of fetuses. After maternal administration of 1 mg PIL, ACE activity fell significantly in fetal serum, placenta and fetal lung, but not in fetal kidney. Ten mg PIL produced a further significant decrease in ACE activity in fetal organs and serum. Plasma renin activity (PRA) was significantly stimulated after PIL administration in both mothers and fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Characteristics of tissue distribution of various polysaccharides as drug carriers: influences of molecular weight and anionic charge on tumor targeting.

Using the Walker 256 model for carcinosarcoma-bearing rats, we intravenously administered 5 polysaccharide carriers with various molecular weights (MWs) and electric charges and tested for their plasma and tissue distribution. Two carriers, carboxymethylated-D-manno-D-glucan (CMMG) and CMdextran (CMDex), showed higher plasma AUC than the other carriers tested, namely, CMchitin (CMCh), N-desulfated N-acetylated heparin (DSH), and hyaluronic acid (HA). This was consistently found to be true over the range of MWs tested. For CMDex, the maximum value of plasma AUC was obtained when the MW exceeded 150 kDa. As for the anionic charge, CMDex (110-180 kDa) with a degree of substitution (DS) of the CM groups ranging from 0.2 to 0.6, showed maximum plasma AUC values. Twenty-four hours after administration, the concentration of CMDex (180-250 kDa; DS: 0.6-1.2) in tumors was more than 3% of dose/g--approximately 10-fold higher than those observed with CMCh, DSH and HA. Doxorubicin (DXR) was bound to these carriers via a peptide spacer, GlyGlyPheGly (GGFG), to give carrier-GGFG-DXR conjugates (DXR content: 4.2-7.0 (w/w)%), and the antitumor effects of these conjugates were tested with Walker 256 carcinosarcoma-bearing rats by monitoring the tumor weights after a single intravenous injection. Compared with free DXR, CMDex-GGFG-DXR and CMMG-GGFG-DXR conjugates significantly suppressed tumor growth, while the CMCh-GGFG-DXR, DSH-GGFG-DXR, and HA-GGFG-DXR conjugates in a similar comparison showed weak tumor growth inhibition. These findings suggest that the antitumor effect of the carrier-DXR conjugates was related to the extent with which the carriers accumulated in the tumors.

Animals↗

PubMed1989

Tissue distribution of RNAs for cystatins, histatins, statherin, and proline-rich salivary proteins in humans and macaques.

The tissue distribution of the mRNAs for a number of salivary proteins [proline-rich proteins (PRPs), statherin, cystatins, and the histatins] has been examined in humans and macaques in order to investigate their possible functions and tissue-specific regulation. We have shown that PRP RNAs (0.8-1.5 kb) are expressed in human and rhesus parotid and submandibular glands, and in the human bronchus. The genes for the acidic and basic PRPs are differentially regulated in these tissues. RNAs for acidic PRPs are predominantly expressed in the submandibular gland, for basic PRPs in the respiratory tract, and for both acidic and basic PRPs in the parotid gland. Protein studies of secretions from these tissues confirm the RNA results. Statherin RNA (0.65 kb) was detected in human and rhesus parotid and submandibular glands and the human bronchus, as well as in rhesus lacrimal glands. Statherin was found by tissue immunoperoxidase staining in the serous cells of respiratory tract submucosal glands, which is the same location for the synthesis of PRPs. Several cystatin RNAs (0.8-1.3 kb) were differentially expressed in human parotid glands, submandibular glands, and the bronchus, and in lacrimal glands from both rhesus and cynomolgus macaques. RNAs (0.6 kb) for the histatins were found only in parotid and submandibular glands. Thus, it appears that PRPs, statherin, and cystatins may play a broader role in the physiology of biological fluids and secretions than previously suspected, since they are found in secretions other than saliva. However, the functions of the histatins are restricted to saliva. These studies also pose some interesting questions regarding the differential expression of these genes in a variety of secretory tissues.

Animals↗

PubMed1992

cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal hydrolase PGP9.5.

We have isolated a cDNA clone encoding ubiquitin carboxyl-terminal hydrolase PGP9.5 from a rat brain cDNA library and examined the tissue distribution. The primary structure of the cDNA consists of 856 nucleotides including the entire coding region for 223 amino acids, and the calculated molecular mass is 24,782 Da. The rat PGP9.5 is strikingly homologous to the human PGP9.5, 75.2% of nucleic acids and 95.1% of amino acids being identical. The mRNA of PGP9.5 is most abundant in the rat brain and to a lesser degree in the testis. In other peripheral tissues we tested, the mRNA was undetectable. Western blotting using an anti-rat PGP9.5 antibody revealed the parallel distribution of mRNA and protein in various brain regions and testis. The availability of the rat PGP9.5 clone provides a new approach to examine the function of PGP9.5 and the role that it plays in the pathology of neurodegenerative diseases.

Amino Acid Sequence↗

PubMed1982

Tissue Distributions of Chlorogenic Acid and of Enzymes Involved in Its Metabolism in Leaves of Sorghum bicolor.

The tissue distributions of cholorgenic acid, chlorogenic acid oxidase, and three other enzymes involved in the metabolism of this secondary (natural) product have been investigated in leaf-blades of light-grown seedlings of Sorghum bicolor. Cholorogenic acid was found only in epidermal and mesophyll protoplasts isolated from the leaf; 60% of the chlorogenic was contained in the epidermal fraction. Nearly all (90%) of the chlorogenic acid oxidase was found in the mesophyll protoplasts. The bundle-sheath strands, on the other hand, contained no chlorogenic acid and essentially none of the oxidase. Three other enzymes required for the synthesis of chlorogenic acid, but also for other plant products, were found in all three tissue fractions.

Journal Article↗

PubMed2005

Tissue distribution and thyroid hormone regulation of Pept1 and Pept2 mRNA in rodents.

Peptide transporters (Pept) have essential physiological functions and also transport various drugs. Information regarding tissue distribution and gene regulation of Pept in rodents is limited. The present study investigated the distribution of Pept1 and Pept2 mRNA in 19 tissues of male and female Sprague-Dawley rats and C57BL/6 mice, as well as thyroid hormone regulation of renal Pept expression in male rats, using the branched DNA signal amplification assay. Pept1 mRNA was not only highly expressed in small intestine, but also detectable in gonads of both species, kidney of rats, and large intestine of mice. Pept2 mRNA was the highest in kidney, followed by brain and lung. The present study offers the first evidence of considerable Pept2 mRNA expression in pituitary and reproductive organs (testis, prostate, ovary, and uterus). Interestingly, Pept2 mRNA expression in mouse prostate appeared to be much higher than that in rat prostate. Thyroidectomy increased Pept1 and Pept2 mRNA in male rat kidney; such increases were abolished by thyroid hormone replacement.

Animals↗

PubMed2004

Correlation between the clinical phenotype of MYH9-related disease and tissue distribution of class II nonmuscle myosin heavy chains.

Nonmuscle myosin heavy chain II-A is responsible for MYH9-related disease, which is characterized by macrothrombocytopenia, granulocyte inclusions, deafness, cataracts, and renal failure. Since another two highly conserved nonmuscle myosins, II-B and II-C, are known, an analysis of their tissue distribution is fundamental for the understanding of their biological roles. In mouse, we found that all forms are ubiquitously expressed. However, megakaryocytic and granulocytic lineages express only II-A, suggesting that congenital features, macrothrombocytopenia, and leukocyte inclusions correlate with its exclusive presence. In kidney, eye, and ear, where clinical manifestations have a late onset, as well as in other tissues apparently not affected in patients, II-A and at least one of the other two isoforms are expressed, suggesting that II-B and II-C can partially compensate for each other. We hypothesize that cells expressing only II-A manifest the congenital defects, while tissues expressing additional myosin II isoforms show either late onset of abnormalities or no pathological sign.

Animals↗

PubMedDate not supplied

Tissue distribution of methamphetamine and amphetamine in premature infants.

An amphetamine-abusing mother who had taken methamphetamine 5 hours before beginning labor gave birth to twins who died 1 to 2 hours after birth; an autopsy and toxicological examination were performed. The results are consistent with previous findings of premature delivery and retarded intrauterine development. Tissue distribution shows a similar pattern to an earlier reported case, though drug concentrations are about 10 times higher.

Amphetamine↗

PubMed2000

Ex vivo measurement of tissue distribution of a nitroxide radical after intravenous injection and its in vivo imaging using a rapid scan ESR-CT system.

To establish the usefulness of ESR-CT imaging with 3-carbamoyl-2,2,5, 5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) in living animals, we investigated the tissue distribution of carbamoyl-PROXYL after i. v. injection. Ten minutes after injection of carbamoyl-PROXYL, its concentrations in the liver, spleen, kidney, and plasma were higher than those in the small intestine and stomach. However, the inter-organ differences in concentrations were not striking. We selected the liver as a representative organ and attempted to measure the concentration of carbamoyl-PROXYL in it after washing out all of the blood by in situ perfusion with saline. The ESR spectrum of the liver homogenate after complete blood washout revealed that the concentration of carbamoyl-PROXYL was significantly reduced. Thus, at this time, carbamoyl-PROXYL was distributed predominantly in the plasma and/or loosely attached to the surfaces of cells. We obtained high-quality ESR-CT images of the murine abdomen at a measurement time of 40 s and found that a high-intensity area of carbamoyl-PROXYL appeared in the liver and kidneys, indicating an abundant blood circulation. Although the organ specificity of carbamoyl-PROXYL was weak, we consider that ESR-CT imaging with carbamoyl-PROXYL will be a powerful new tool for non-invasive anatomic analysis of the liver and the kidneys.

Animals↗

PubMed1995

Stability, tissue metabolism, tissue distribution, and blood partition of DA-1131, a new carbapenem.

The stability of DA-1131 after incubation in various pH solutions, human plasma, human urine, human gastric juice, rat liver homogenates and rat whole blood, the disappearance of DA-1131 after incubation in the 9000g supernatant fraction of various rat tissue homogenates in the presence of NADPH, the tissue distribution of DA-1131 after intravenous (i.v.) administration of DA-1131, 50 mg/kg, to rats, and the blood partition of DA-1131 between plasma and blood cells from rabbit blood were studied. DA-1131 was unstable when incubated in various pH solutions, especially at low and high pHs at the DA-1131 concentration of 10 micro g/ml; the degradation half-lives of DA-1131 were 0.260, 1.23, 2.20, 7.16, 14.2, 10.5, 31.3, 21.3, 0.262, 0.241, and 1.45 hr for pH solutions of 1-11, respectively. DA-1131 was also unstable after incubation in human plasma, rat liver homogenates, and human gastric juice. However, DA-1131 seemed to be sable in human plasma for up to 12 hr storage at -20 degrees C. The spleen, kidney, liver, lung, mesentery, and stomach homogenates from rats showed metabolic activity to DA-1131. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The plasma-to-blood cell concentration ratios of DA-1131 were independent of DA-1131 blood concentrations when the whole blood was incubated up to 120 min; the mean values were 5.56 +/- 1.47, 5.80 +/- 2.19, and 4.61 +/- 1.82 at DA-1131 blood concentrations of 2, 10, and 20 microgram/ml, respectively, rabbits A-C. There was also considerable in vivo and in vitro blood storage effect in the plasma concentration of DA-1131 in rabbits.

Animals↗

PubMed2000

Pharmacokinetics and tissue distribution of a ribozyme directed against hepatitis C virus RNA following subcutaneous or intravenous administration in mice.

A nuclease resistant ribozyme targeting the 5' untranslated region (5' UTR) of hepatitis C virus (HCV) at site 195 has been identified. To investigate the therapeutic utility of this ribozyme, we evaluated the pharmacokinetics and tissue distribution with two labeled forms of this ribozyme. [(32)P]-labeled ribozyme was administered as a single subcutaneous (SC) or intravenous (IV) bolus at a dose of 10 mg/kg or 30 mg/kg in C57Bl/6 mice. Regardless of route of administration, peak liver concentrations achieved were greater than the concentration necessary to inhibit HCV-IRES-luciferase expression in cell culture. The ribozyme was well absorbed after SC administration (89%) and had an elimination half-life of 23 minutes. To show intracellular localization of the ribozyme in target tissue, a tetramethyl rhodamine (TMR)-labeled ribozyme was administered as a single SC or IV bolus at a dose of 30 mg/kg in C57Bl/6 mice. Mice treated SC or IV with TMR-labeled ribozyme had positive fluorescence in the liver from 15 minutes to 48 hours after dosing. Definite positive fluorescence was still present at 72 hours in the mice dosed via the IV route. At early time points (15 and 30 minutes postinjection), nuclear and possibly cytoplasmic fluorescence was present in the hepatocytes, and sinusoidal fluorescence was intense. At the later time points, fluorescence became more punctate. Abundant staining was often present in Kupffer cells. This study confirms the retention of ribozyme in liver cells and supports the potential of an anti-HCV ribozyme as a therapeutic agent for treatment of chronic hepatitis C.

Animals↗

PubMed1997

Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse.

Until recently, only a single type of estrogen receptor (ER) was thought to exist and mediate the genomic effects of the hormone 17beta-estradiol in mammalian tissues. However, the cloning of a gene encoding a second type of ER, termed ERbeta, from the mouse, rat, and human has prompted a reevaluation of the estrogen signaling system. Based on in vitro studies, the ERbeta protein binds estradiol with an affinity similar to that of the classical ER (now referred to as ERalpha) and is able to mediate the effects of estradiol in transfected mammalian cell lines. Essential to further investigations of the possible physiological roles of ERbeta, and its possible interactions with ERalpha, are data on the tissue distribution of the two ER types. Herein, we have described the optimization and use of an RNase protection assay able to detect and distinguish messenger RNA (mRNA) transcripts from both the ERalpha and ERbeta genes in the mouse. Because this assay is directly quantitative, a comparison of the levels of expression within various tissues was possible. In addition, the effect of disruption of the ERalpha gene on the expression of the ERbeta gene was also investigated using the ERalpha-knockout (ERKO) mouse. Transcripts encoding ERalpha were detected in all the wild-type tissues assayed from both sexes. In the female reproductive tract, the highest expression of ERbeta mRNA was observed in the ovary and showed great variation among individual animals; detectable levels were observed in the uterus and oviduct, whereas mammary tissue was negative. In the male reproductive tract, significant expression of ERbeta was seen in the prostate and epididymis, whereas the testes were negative. In other tissues of both sexes, the hypothalamus and lung were clearly positive for both ERalpha and ERbeta mRNA. The ERKO mice demonstrated slightly reduced levels of ERbeta mRNA in the ovary, prostate, and epididymis. These data, in combination with the several described phenotypes in both sexes of the ERKO mouse, suggest that the biological functions of the ERbeta protein may be dependent on the presence of ERalpha in certain cell types and tissues. Further characterization of the physiological phenotypes in the ERKO mice may elucidate possible ERbeta specific actions.

Animals↗

PubMed1982

Radiotracers binding to estrogen receptors: I: Tissue distribution of 17 alpha-ethynylestradiol and moxestrol in normal and tumor-bearing rats.

Ethynylestradiol and moxestrol can be labeled with carbon-11 by introducing this positron emitter in the 17 alpha-ethynyl group. To investigate their potential as radiotracers binding to estrogen receptors, we studied the tissue distribution of tritiated ethynylestradiol and moxestrol, with specific activities of 57 Ci/mmol and 77-90 Ci/mmol, respectively, in the adult female rat. At 30 min after injection, both compounds showed specific uptake in the uterus (% dose/g): 2.52 for ethynylestradiol and of 2.43 for moxestrol. A decrease of the specific activity to 6-9 Ci/mmol resulted in uterine uptakes of 1.60 and 2.10 respectively, for ethynylestradiol and moxestrol, at 30 min. In the female rat bearing DMBA-induced mammary tumors, specific uptake was also measured in the tumors, although the values were only 25-30% of the uterine uptake. Moxestrol showed a greater uptake selectivity in the tumors compared with ethynylestradiol. From this study we conclude that ethynylestradiol and moxestrol have good potential as tracers binding to mammary tumors that contain estrogen receptors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

Tissue distribution of a melanoma-associated antigen immunogenic in patients with melanoma as analyzed by polyclonal antibodies to recombinant peptide antigen.

This study aimed to detect in vivo expression of human melanoma-associated antigen D-1, which was identified by screening an expression cDNA library constructed from mRNA extracted from cultured melanoma cells with sera from patients with melanoma. The tissue distribution of D-1 antigen was then analyzed. Murine anti-D-1 recombinant peptide polyclonal antibodies were raised by immunization of in vitro synthesized D-1 peptide against Balb/c mice and applied immunohistochemically on paraffin-embedded tissue specimens. D-1 antigen was found to be restrictedly expressed on melanoma cells, but not on normal melanocytes, adjacent keratinocytes, fibroblasts, lymphocytes and adnexal structures of skin. The reactivities of anti-D-1 antibodies did not correlate with histogenesis of the lesions, their ability to produce melanin, and/or their primary or metastatic nature. There was no positive reactivity of anti-D-1 antibodies with other skin tumors, including squamous cell carcinoma, basal cell epithelioma, seborrheic keratosis, and nevus cell nevus. Further, cytoplasmic expression of D-1 antigen in melanoma cells was observed only in a certain subgroup of patients with melanoma. This indicates that the cell surface expression of D-1 peptide requires specific transporting proteins, such as HLA molecules.

Animals↗

PubMed2005

Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in two freshwater shrimps, Palaemon modestus and Macrobrachium nipponensis, from a large shallow, eutrophic lake of the subtropical China.

So far no information is available on microcystin (MC) contents in shrimps, prawns or crayfish from natural freshwaters. Tissue distributions and seasonal dynamics of the hepatotoxic MC-LR and -RR in two freshwater shrimps, Palaemon modestus and Macrobrachium nipponensis were studied monthly (during June-November, 2003) in a Chinese lake containing toxic cyanobacterial blooms. The shrimps P. modestus and M. nipponensis accumulated high MCs not only in the hepatopancreas (mean 4.29 and 0.53 microg g(-1) DW, respectively) but also in the gonad (mean 1.17 and 0.48 microg g(-1) DW, respectively), and the crayfish Procambarus clarkii accumulated as much as 0.93 microg g(-1) DW in the gonad. This indicates that gonads of these invertebrates are the second important target organ of MCs. P. modestus apparently accumulated more MCs in their organs than M. nipponensis, which might be a reflection of their difference in trophic niche. Eggs of the shrimps accumulated 8.4% (M. nipponensis, 0.27 microg g(-1) DW) and 29.0% (P. modestus, 2.34 microg g(-1) DW) of total toxin burden, indicating that MCs had been transferred into offspring from their adults. Among the shrimp muscle samples analyzed, 31% were above the provisional WHO TDI level, suggesting the risk of consuming shrimps in Lake Chaohu.

Animals↗

PubMed2004

Death during patient-controlled analgesia: piritramide overdose and tissue distribution of the drug.

We report about a fatality during patient-controlled analgesia (PCA). Piritramide peripheral blood concentration was measured with 0.1 mg/l and exceeded the normal therapeutic range. Therefore, a fatal overdose was considered as the cause of death with respiratory depression as the underlying pathophysiological mechanism. The tissue distribution was studied; highest concentrations of piritramide were measured in kidney, bile and urine. Due to a large volume of distribution a difference in the drug concentration found in heart and peripheral bloods the phenomenon of drug redistribution was observed. Confronted with toxicological results, investigations revealed, that the PCA pump had been changed during a previous servicing from displaying mg/h to ml/h, therefore, the anesthetist had entered "1.5" assuming mg/h, but actually applying 1.5 ml/h (which was therefore equivalent to 2.25 mg/h, given a concentration in the cartridge of 1.5 mg piritramide/ml). In total, 61.5 ml (instead of 61.5 mg) had been infused, equivalent to 92.25 mg piritramide. This case report is a further example that human errors can play a crucial role in the safety of medical equipment. Experts in anesthesia recommended human factors engineering design principles to improve the safety of medical devices.

Analgesia, Patient-Controlled↗

PubMed2001

Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties.

We have determined the pharmacokinetics of liposomal vincristine, in a Lewis lung carcinoma solid tumor model in mice, with the aim of differentiating the contribution of liposomal and nonliposomal (released from liposomes) drug pools to the overall pharmacokinetic profile. Two types of liposomal formulations were used: one composed of 1,2 distearoyl-sn-glycero-3-phosphocholine/cholesterol (Chol) (55/45; mol/mol) and the other composed of sphingomyelin/cholesterol (SM/Chol; 55/45; mol/mol). Vincristine elimination from the circulation after injection of conventional, aqueous formulated vincristine (C-VINC) was characterized by a short half-life (1.36 h), low plasma area under the plasma concentration-time curve (AUC) (0.59 microg x h/ml), and large volume of distribution (145 ml). Total drug elimination from the circulation after liposomal vincristine injection using SM/Chol liposomes was characterized by a prolonged half-life (6.6 h), increased plasma AUC (213 microg x h/ml) and small volume of distribution (2.0 ml). Our results indicate that > or =98% of the total vincristine measured in the plasma of mice administered with liposomal vincristine was encapsulated within the liposomes. The systemic exposure to free drug after administration of liposomal formulations was significantly lower than that observed after the injection of C-VINC. Plasma concentrations of free drug remained between 0.025 and 0.05 microg/ml over 4 h of postinjection for both liposomal formulations. In contrast, concentrations between 0.1 and 0.35 microg/ml were observed following C-VINC administration. Free plasma drug concentrations did not correlate with vincristine tissue distribution properties following administration of liposomal vincristine formulations. Rather, accumulation of vincristine in tissues appeared to be influenced primarily by the drug retention properties of the liposome. While the reduced systemic exposure to free vincristine correlates with reduced toxicity, additional information (such as liposome drug release properties) may be necessary to correlate pharmacokinetic behavior with antitumor activity.

Animals↗

PubMed2000

Kinetics of peptide uptake and tissue distribution following a single intranasal dose of peptide.

We have previously used intranasal (i.n.) peptide application to induce mucosal tolerance in experimental autoimmune encephalomyelitis (EAE). This strategy, however, appeared to give rise to similar phenomena of tolerance observed as a result of systemic administration of soluble antigenic peptide. We were interested, therefore, in the uptake and tissue distribution of peptide following i.n. treatment. In the H-2u mouse model of EAE, the highly tolerogenic peptide analogue Ac1-9[4Y] of myelin basic protein (MBP) displays high affinity binding to Au MHC class II. For the purpose of the present study this peptide was synthesised to contain a tritiated acetyl group and a protocol was developed to recover radioactivity in solubilised tissues taken at various times after [3H]Ac1-9[4Y] i.n.. Radiolabel loads of the lung and gastro-intestinal tract were initially high but declined rapidly. Radiolabel uptake by blood and lymphoid tissues followed similar kinetics with peak levels around 2.5-4 hours after i.n. administration. Concentrations were high in the draining cervical lymph nodes (CLN) but also reached significant levels in the spleen and 'nondraining' inguinal lymph nodes. The presence of intact antigenic peptide was demonstrated in spleens and CLN from Ac1-9[4Y] i.n. treated mice. Cell suspensions prepared from these tissues at selected time points after peptide i.n. were able to stimulate peptide-specific T cell lines up to at least one day after peptide i.n., suggesting long lasting formation of stable Au-Ac1-9[4Y] complexes in vivo.

Administration, Intranasal↗