Tissue and Hepatic Subcellular Distribution of Liposomes Containing Bleomycin after Intravenous Administration to Patients with Neoplasms

1976 ◽  
Vol 51 (4) ◽  
pp. 421-425 ◽  
Author(s):  
A. W. Segal ◽  
G. Gregoriadis ◽  
J. P. Lavender ◽  
D. Tarin ◽  
T. J. Peters

1. Liposomes containing 111In-labelled bleomycin were injected intravenously into two patients. One patient had a hepatoma and the other had secondary adenocarcinomatous deposits in the liver. 2. The tissue distribution of 111In was determined by whole-body scanning and by measurement of the radioactivity in organs at autopsy. 3. Scans in vivo and post-mortem measurement of radioactivity indicated that liposomes accumulate predominantly in the liver, but that there is no selective uptake of liposomes by the malignant tissue. 4. The subcellular distribution of radioactivity in the liver was measured 90 min after injection by fractionation of percutaneous liver biopsies on sucrose density gradients. 5. Radioactivity within the liver was concentrated in lysosomes. 6. Electron microscopy of tissue obtained before the administration of liposomes revealed particles morphologically indistinguishable from liposomes in hepatoma cells and hepatocytes.

2005 ◽  
Vol 16 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Newton Sesma ◽  
Dalva Cruz Laganá ◽  
Susana Morimoto ◽  
Carlos Gil

This study evaluated, in vivo, the efficacy of a denture glazing material (Palaseal) in modifying plaque colonization of dentures. Ten subjects were selected and received maxillary temporary partial removable dentures, with complete acrylic palatal coverage. The right half of the fitting surface of the denture bases were glazed with Palaseal, whereas the other half was not glazed. One month after insertion, two fragments of the resin base of all dentures were removed (one from the glazed side and another from the non-glazed side). These samples were prepared and examined by scanning electron microscopy. Three months after insertion, other fragments were obtained and analyzed. Microscopic observation at 1 month revealed that, for all patients, the plaque film was thinner on the treated side in comparison to the non-treated side. However, at the 3-month evaluation, some areas of the glaze showed cracking, and both glazed and non-glazed sides were covered by a dense bacterial plaque film. In conclusion, the findings of this clinical experiment showed that glazing denture's fitting surface did not prevent bacterial colonization, but favored plaque removal while the glaze layer remained intact. After three months, glaze cracks created microretentive areas that increased plaque accumulation.


1995 ◽  
Vol 60 (1) ◽  
pp. 143-149 ◽  
Author(s):  
M. Theau-Clément ◽  
N. Michel ◽  
J. Esparbié ◽  
G. Bolet

Male rabbits aged from 4 to 4·5 months were subjected to a 8L: 16D photoperiod for 4 weeks and were then split into two groups. One group of13 males was maintained at 8L: 16D (group 8). The other included 16 males and was submitted to 16L: 8D (group 16). Two successive ejaculates zvere collected and analysed once a week for 6 months. Animals from group 8 were sexually more active and ejaculated significantly larger volumes of semen than those from group 16. Performance of males from group 16 was better for all other measurements, whether these were qualitative (motility, percentage of live spermatozoa) or quantitative. Averages for the total number of spermatozoa and number of live spermatozoa per ejaculate were significantly greater in males submitted to 16L: 8D (509 and 408 v. 452 and 344 × 106 spermatozoa, respectively). However the testes of rabbits in group 8 had a significantly greater volume than those in group 16 (22·3 v. 17·4 cm3, P < 0·001). After the animals were slaughtered when 11 months of age, the volume and weight of the testes and the testis and epidydimis reserves did not differ significantly between groups. Under our experimental conditions, the sperm output of bucks exposed to 16 h of daylength was greater than that of bucks exposed to 8 h of daylength but in vivo and post-mortem measurements did not reflect this difference.


1975 ◽  
Vol 34 (3) ◽  
pp. 501-509 ◽  
Author(s):  
Christine D. Thomson ◽  
Bridget A. Robinson ◽  
R. D. H. Stewart ◽  
Marion F. Robinson

1. The long-term fate in rats of an oral dose of [75Se]selenocystine was compared with that of an oral dose of [75Se]selenomethionine.2. Urinary and faecal radioactivities were measured during the 1st week and whole-body radioactivity was determined for 10 weeks. Rats were killed at weekly intervals for 4 weeks and at weeks 6 and 10 for analysis of tissue distribution of 75Se.3. Intestinal absorption of [75Se]selenocystine was 81% of the administered dose; that of [75Se]selenomethionine was 86%. Urinary excretion of absorbed [75Se]selenocystine was 13.9% and that of [75Se]selenomethionine was 5.8%, in the 1st week.4. Whole-body retention of 75Se was greater for [75Se]selenomethionine than for [75Se]-selenocystine but after the 1st week it decreased at a similar rate in both groups. Tissue distribution of retained 75Se was also similar in both groups.5. The initial utilization of [75Se]selenocystine was different from that of [75Se]selenomethionine. However, after the 1st week 75Se from both sources appeared to be metabolized similarly, suggesting that dietary Se of both forms is ultimately incorporated into the same metabolic pool.6. When these findings were compared with those of earlier studies with [75Se]selenite and 75Se incorporated in vivo into rabbit kidney (RK-75Se) (Thomson, Stewart & Robinson, 1975) the metabolism of [75Se]selenocystine resembled that of [75Se]selenite and RK-75Se, rather than that of [75Se]selenomethionine.


1974 ◽  
Vol 142 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Eric H. Karunanayake ◽  
David J. Hearse ◽  
Graham Mellows

[14C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity of synthetic streptozotocin was characterised by studies in vivo of its diabetogenic activity and its dose–response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-14C]streptozotocin and [2′-14C]streptozotocin the injected radioactivity was excreted (approx. 70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8% respectively) were found in the faeces. In contrast, with [3′-methyl-14C]streptozotocin a much smaller proportion (approx. 42%) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53% of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3′-methyl-14C]streptozotocin. There was no accumulation of [1-14C]streptozotocin in the pancreas for the 6h period after administration. However, with [3′-methyl-14C]streptozotocin (and also [2′-14C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.


1998 ◽  
Vol 10 (6) ◽  
pp. 459 ◽  
Author(s):  
T. G. McEvoy ◽  
K. D. Sinclair ◽  
P. J. Broadbent ◽  
K. L. Goodhand ◽  
J. J. Robinson

Large fetuses arising from embryos produced in vitro have been shown to exhibit altered organ development in utero, but it is not known whether this persists post natally. Post-natal growth and development was examined in 18 Simmental bulls derived from in vivo frozen–thawed (n = 6), in vitro frozen– thawed (n = 6) or in vitro fresh (n = 6) embryos and reared together post weaning on an ad libitum diet until slaughter at approximately 13 months old. Calves weighing less than 60 kg at birth (n = 11) were classified as normal, and heavier calves (n = 7; all from in vitro embryos) as oversize. Lifetime growth rates and slaughter weights apparently were unaffected by embryo source or birthweight. Mean (± s.e.m.) post mortem liver and kidney weights were unaffected by embryo source, but hearts of bulls from in vitro frozen embryos were heavier than those of bulls from in vivo frozen embryos (2.7 ± 0.04 v. 2.3 ± 0.07 kg, P<0.025). Heart weight per kilogram body weight at slaughter for the 7 perinatally oversize males (4.01 ± 0.08 g) exceeded that of the other 5 bulls from in vitro embryos (3.60 ± 0.10 g kg −1 ; P<0.04) and the 6 in vivo males (3.56 ± 0.12 g kg −1 ; P<0.02). Overall, one-third of the variation in heart weight at slaughter (r 2 = 0.35; P = 0.01) was due to variation in birthweight. This is the first study to demonstrate birthweight-related developmental effects on post-natal organ weight following the transfer of embryos produced in vitro.


1999 ◽  
Vol 160 (2) ◽  
pp. 205-216 ◽  
Author(s):  
JA Tresguerres ◽  
C Ariznavarreta ◽  
B Granados ◽  
P Alvarez-Vega ◽  
P Fernandez-Mateos ◽  
...  

To test whether salivary tissue can secrete pituitary hormones, female Sprague-Dawley rats were hypophysectomized (hypox) and the following were transplanted to the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30), muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with dentist's cement. In addition a group of rats (group 1, n=22) remained intact as controls. All groups were followed for 8 months. Daily vaginal smears showed normal cyclicity in controls and constant dioestrus in all hypox groups. Blood samples, taken once every 30 days before and after LHRH stimulation, showed significantly lower (P<0.001) plasma LH values in all hypox groups compared with controls. In group 3, a gradual and significant increase (P<0.05) was observed in the LH response to LHRH in parallel with a partial recovery of oestrous smears. No LH modification was observed in the other hypox groups. Plasma prolactin (PRL) levels were also very low in all hypox groups and were unaltered throughout the study. At the end of the experiments, half the animals were killed by decapitation and the hypothalamic-pituitary areas carefully dissected, homogenized and analysed for LH and PRL content. The remaining animals were perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues. Hypothalamic and transplant areas were carefully dissected, frozen, cut and submitted to immunochemical procedures. LH content in the graft of group 3 animals was markedly (P<0.001) lower than in the control pituitary, but significantly higher (P<0.05) than in the other hypox groups. Immunochemistry showed LH and PRL positive cells in the graft of group 3 animals, whereas neither positive cells, nor LH content were observed in the parotid gland in situ. Experiments were completed with in vitro cultures of parotid glands in the presence or absence (controls) of synthetic hypothalamic hormones or rat hypothalamic extracts. After 1.5 weeks of culture, a significantly higher LH concentration (P<0.05) was observed in the wells treated with synthetic hypothalamic hormones (216+/-46 pg/ml vs 41+/-6 pg/ml in controls). When hypothalamic extracts were used, the LH levels increased more markedly (1834+/-190 pg/ml vs 36+/-6 pg/ml in controls) and those values were maintained during 3 weeks of culture. Immunostaining of these cultures showed a positive LH reaction in the epithelial cells found in the hypothalamic extract-treated wells. Both in vivo and in vitro studies confirm the transdifferentiation of parotid gland tissue to pituitary hormone-producing cells under hypothalamic influence.


1899 ◽  
Vol 45 (191) ◽  
pp. 758-760
Author(s):  
E. B. Whitcombe

The patient, thirty-nine years of age, was admitted into Birmingham Asylum in February, 1898. He was a porter, married, in fairly robust condition, and was a typical example, both mentally and physically, of general paralysis of the insane of somewhat short duration. He was stated to have been steady, of temperate habits, and had been in the army. For twelve years he served in India. No history of fevers or other illness. The disease progressed without any special features until January 14th of this year, when he was noticed to be worse; his breathing was a little rapid, and in consequence he was sent to the infirmary ward and was examined thoroughly by the assistant medical officer, who found nothing specially interesting, but ordered him to be put to bed and kept warm. This was about 3 o'clock in the afternoon. At 7 o'clock the same evening I was asked to see the patient (he had been examined at 5 o'clock by the nurse). I found the left leg from thigh to toe was double the size of the other leg, and nearly the whole surface of the leg was perfectly black, and there were numerous large bullæ the size of one's fist in different places along the leg. There was no special line of demarcation. At first sight it looked like an extreme case of local purpura, but after a careful examination I came to the conclusion that putrefaction had actually set in, and that the man was dying, and death took place an hour after I saw him. The most extraordinary part of this case occurred afterwards. I am accustomed to go and see a body before giving my certificate to the coroner. I saw this man between 10 and 11 on Sunday morning, he having died at 8 p.m. on Saturday. The body was double the former size; it was more like the body of a negro, the whole surface being in a black condition, and the bullæ had increased on the other parts of the body. The scrotum was distended to the size of a man's head, and the penis swelled and distorted. The case was the more extraordinary as the highest temperature recorded locally at the time was 52·8°, and the lowest 34°. I personally saw the coroner, and together we went through numerous works on jurisprudence, but we could find nothing to give us any idea as to the cause of this condition, and he very kindly and in scientific interests ordered an inquest. He sent Dr. Simon, Professor of Medical Jurisprudence in Mason College, to make the post-mortem examination. The results were practically nil, the whole body internally and externally being putrefied. The cause of death was very naturally put down to general paralysis, but as to any cause for this extremely rapid putrefaction we could arrive at no conclusion. The case is one of very great interest. I believe that the first idea that the nurse had in the infirmary was that this man must have been injured. Now there was the usual considerable difference between the appearance of an injury and this condition, which looked like purpura; but besides this the difficulty that occurred to my mind was as to the fixing of the time of death. Here was a body presenting the appearances which are usually recognised as those of three or four weeks' duration, and these had happened certainly within sixteen hours. From the point of view of jurisprudence it occurred to me that a murder might be committed, that the body might present these appearances, and that it would be a most serious matter for a medical man to give an opinion as to the time of death. We know that in hot countries this condition does occur, but we were in the middle of winter, and the condition arose from, so far as we could judge, no special cause whatever. There was some atheroma of the arteries, but otherwise we could distinguish nothing of importance at the post-mortem. It is to be regretted that no bacteriological examination was made.


2008 ◽  
Vol 19 (1) ◽  
pp. 207-215 ◽  
Author(s):  
Justin M. Kollman ◽  
Alex Zelter ◽  
Eric G.D. Muller ◽  
Bethany Fox ◽  
Luke M. Rice ◽  
...  

The γ-tubulin small complex (γ-TuSC) is an evolutionarily conserved heterotetramer essential for microtubule nucleation. We have determined the structure of the Saccharomyces cerevisiae γ-TuSC at 25-Å resolution by electron microscopy. γ-TuSC is Y-shaped, with an elongated body connected to two arms. Gold labeling showed that the two γ-tubulins are located in lobes at the ends of the arms, and the relative orientations of the other γ-TuSC components were determined by in vivo FRET. The structures of different subpopulations of γ-TuSC indicate flexibility in the connection between a mobile arm and the rest of the complex, resulting in variation of the relative positions and orientations of the γ-tubulins. In all of the structures, the γ-tubulins are distinctly separated, a configuration incompatible with the microtubule lattice. The separation of the γ-tubulins in isolated γ-TuSC likely plays a role in suppressing its intrinsic microtubule-nucleating activity, which is relatively weak until the γ-TuSC is incorporated into higher order complexes or localized to microtubule-organizing centers. We propose that further movement of the mobile arm is required to bring the γ-tubulins together in microtubule-like interactions, and provide a template for microtubule growth.


1977 ◽  
Vol 38 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Margaret Richold ◽  
Marion F. Robinson ◽  
R. D. H. Stewart

1.[75Se]selenite or [75Selenomethionine was injected into the coelomic cavity of fish. After 2 d or 14 d the muscle portion of the fish was removed and homogenized. The long-term fate in rats of an oral dose of each labelled homogenate was compared with that of an oral dose of [75Se]selenite or [75Se]selenomethionine mixed with unlabelled fish homogenate.2.Urinary and faecal radioactivity were measured during the 1st week and whole-body radioactivity was determined for 10 weeks. Rats were killed at weekly intervals for 4 weeks for analysis of tissue distribution of 75Se.3.Intestinal absorption of 75Se given as labelled fish homogenate was less complete than that of 75Se mixed with unlabelled homogenate, and the absorption of 75Se from the 14d-labelled fish homogenate derived from [75Se]selenite was less complete than that of 75Se from the other labelled homogenates.4.Urinary excretion of absorbed 75Se in the first 7 d was in the range 5-8 % absorbed dose and was slightly greater in the rats given 75Se as selenite or derived from selenite than in those given 75Se as selenomethionine or derived from selenomethionine. Endogenous faecal excretion of absorbed Se was similar in all groups, as also were tissue distribution of retained 75Se and long-term whole-body turnover rate.5.The results of these studies are compared with those of earlier studies of the metabolism in rats of [75Selenomethionine, [75Se]selenite, [75Sejselenocystine and 75Se incorporated in vivo into rabbit kidney. There were differences in the initial utilization of 75Se from these various sources but after the 1st week 75Se from all sources appeared to be metabolized similarly, suggesting that for rats dietary Se of all forms is ultimately incorporated into the same metabolic pool.


2010 ◽  
Vol 104 (2) ◽  
pp. 204-213 ◽  
Author(s):  
R. Poureslami ◽  
G. M. Turchini ◽  
K. Raes ◽  
G. Huyghebaert ◽  
S. De Smet

The present study was conducted to evaluate the effect of different dietary lipid sources, age and sex on the SFA and MUFA metabolism in broiler chickens using a whole body fatty acid balance method. Four dietary lipid sources (palm fat, Palm; soyabean oil, Soya; linseed oil, Lin; and fish oil, Fish) were added at 3 % to a basal diet containing 5 % Palm. Diets were fed to female and male chickens from day 1 to either day 21 or day 42 of age. The accumulation (percentage of net intake andex novoproduction) of SFA and MUFA was significantly lower in broilers fed on Palm than in broilers fed on the other diets (85·7v.97·4 %). Conversely, β-oxidation was significantly higher in Palm-fed birds than the average of the other dietary treatments (14·3v.2·6 %). On average, 33·1 % of total SFA and MUFA accumulated in the body were elongated, and 13·8 % were Δ-9 desaturated to longer chain or more unsaturated metabolites, with lower proportions being elongated and desaturated for the Palm and Fish diets than for the Soya and Lin diets. Totalin vivoapparent elongase activity decreased exponentially in relation to the net intake of SFA and MUFA, while it increased with age. Totalin vivoapparent Δ-9 desaturase activity was not significantly affected by dietary treatment or age. Totalex novoproduction and β-oxidation of SFA and MUFA showed a negative and positive curvilinear relationship with net intake of SFA and MUFA, respectively. Sex had no effect on SFA and MUFA metabolism.


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