The gastrointestinal absorption of organically bound forms of plutonium in fed and fasted hamsters

Values of about 0.005-0.01 per cent were obtained for the absorption in fed hamsters of plutonium ingested as Pu4+ citrate, isocitrate, phytate and malate complexes and Pu3+ ascorbate compared with about 0.003-0.004 per cent for Pu4+ nitrate. Replacing drinking water with tea did not affect the result for Pu4+ nitrate. Fasting hamsters for 8 h before the administration of plutonium citrate increased absorption to 0.1-0.2 per cent. An extra period of fasting for 4 h after administration did not lead to a further increase in absorption. Similar values were also obtained when plutonium citrate was administered after a 24 h fast, followed either by immediate access to food or a further 4 h fast. In hamsters fasted for 24 h before administration of either Pu3+ ascorbate or Pu4+ nitrate, about 6-7 per cent of the ingested plutonium was retained in the gastrointestinal tract after one week. At three weeks after ingestion of Pu3+ ascorbate, gastrointestinal retention had fallen 100-fold without an increase in absorption.     

The possible protective effect of cysteine during acute alcohol intoxication]

In the experimental conditions used, cysteine administered per os together with ethanol reduces the blood alcohol levels, but does not modify significantly the rate of alcohol oxidation. No effect of cysteine administration is however observed when ethanol is injected intraperitoneally. Cysteine addition in vitro enhances ethanol consumption by liver slices and reduces at the same time 14CO2 production from [2-14C] ethanol. This effect is only observed with a high cysteine/ethanol molar ratio. The changes in the blood alcohol level resulting from cysteine administration do not appear to result from such an interaction with ethanol oxidation, but seem to be due to a delayed ethanol absorption from the gastrointestinal tract.     

Biodistribution and stability of CdSe core quantum dots in mouse digestive tract following per os administration: advantages of double polymer/silica coated nanocrystals

CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) to stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials - mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) - are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract.     

Colorimetric analysis with N,N-dimethyl-p-phenylenediamine of the uptake of intravenously injected horseradish peroxidase by various tissues of the rat

1. A method is described for the colorimetric determination of peroxidase with N,N-dimethyl-p-phenylenediamine. The amount of red pigment formed by peroxidase is proportional to the concentration of enzyme and to the time of incubation during the first 40 to 90 seconds. The influence of the concentration of enzyme, N,N-dimethyl-p-phenylenediamine, H(2)O(2), the time of incubation, pH, the temperature, and the possible interference by oxidizing and reducing agents of tissues has been tested. 2. The method has been used to follow the uptake of intravenously injected horseradish peroxidase by 18 different tissues of the rat over a period of 30 hours. The highest concentration of the injected tracer enzyme was found in extracts of kidney, liver, bone marrow, thymus, and spleen. Considerable amounts were taken up by pancreas, prostate, epididymis, and small intestine. Lower concentrations were found in extracts of lung, stomach, heart, and skeletal muscle, aorta, skin, and connective tissue. No uptake was observed by brain and peripheral nerve tissue. 3. Tissue homogenates containing high concentrations of the injected peroxidase, in general also showed high or average activity of acid phosphatase. 4. Six hours after intravenous administration, the liver contained 27 per cent, the kidney 12 per cent, and the spleen, 1.4 per cent of the injected dose. 5. Approximately 20 per cent of the injected peroxidase was excreted in the urine during the first 6 hours, and the concentration of peroxidase in blood serum and urine fell exponentially during this time. After 6 hours, only low concentrations were excreted in the urine but low enzyme activity was still detectable after 30 hours. Approximately 6 per cent of the injected dose was excreted in the feces from 6 to 20 hours after administration. 6. After feeding through a stomach tube, low concentrations of peroxidase were found in blood serum and urine. Considerable variations in the extent of absorption from the gastrointestinal tract were observed in individual rats.     

Experimental characteristics of the antileishmaniasis action of amphotericin B]

The efficacy of amphotericin B powder of the Soviet production was studied as a therapeutic agent in experimental zoonotic leishmaniosis of the skin form of mice and hamsters. Amphotericin B was administered per os and its action was compared with that of monomycin injected subcutaneously (50 mg/kg). Amphotericin B in a dose of 150 mg/kg administered for 30 days protected 96+/-0.07 and 76.4+/-0.9 per cent of the mice and hamsters respectively from development of the leishmaniosis clinical signs, 68.8+/-0.04 per cent of the animals being cured (in the treatment experiments). The effect of the antibiotic was analogous to that of monomycin administered parenterally. The study of the kinetics of amphotericin B showed that the antibiotic was well absorbed from the digestive tract of the animals into the blood which provided the chemotherapeutic effect.     

Absorption, serum levels and urinary excretion of inorganic sulfate after oral administration of sodium sulfate in the conscious rat.

The absorption of inorganic sulfate after ingestion was investigated in rats. After oral administration of Na235SO4, 35S radioactivity was measurable in plasma already after 15 min and its plasma concentration reached a peak after about 1.5--2 h. The 35S-radioactivity excreted in urine during 24 h after ingestion of Na235SO4 together with varying amounts of unlabelled Na2SO4 (0.25--5.0 mmol Na2SO4 per rat) indicated an almost complete absorption of inorganic sulfate from the gastrointestinal tract. Determination of the inorganic sulfate concentration in rat serum 2 h after oral administration of 5.0 mmol Na2SO4 revealed a three-fold increase in serum sulfate concentration. The data suggest a rapid and almost complete absorption of inorganic sulfate after oral administration in the rat. Its importance in relation to the sulfate availability for sulfate conjugation of drugs is discussed.     

Colorimetric Analysis with N,N-Dimethyl-p-phenylenediamine of the Uptake of Intravenously Injected Horseradish Peroxidase by Various Tissues of the Rat

1. A method is described for the colorimetric determination of peroxidase with N,N-dimethyl-p-phenylenediamine. The amount of red pigment formed by peroxidase is proportional to the concentration of enzyme and to the time of incubation during the first 40 to 90 seconds. The influence of the concentration of enzyme, N,N-dimethyl-p-phenylenediamine, H₂O₂, the time of incubation, pH, the temperature, and the possible interference by oxidizing and reducing agents of tissues has been tested. 2. The method has been used to follow the uptake of intravenously injected horseradish peroxidase by 18 different tissues of the rat over a period of 30 hours. The highest concentration of the injected tracer enzyme was found in extracts of kidney, liver, bone marrow, thymus, and spleen. Considerable amounts were taken up by pancreas, prostate, epididymis, and small intestine. Lower concentrations were found in extracts of lung, stomach, heart, and skeletal muscle, aorta, skin, and connective tissue. No uptake was observed by brain and peripheral nerve tissue. 3. Tissue homogenates containing high concentrations of the injected peroxidase, in general also showed high or average activity of acid phosphatase. 4. Six hours after intravenous administration, the liver contained 27 per cent, the kidney 12 per cent, and the spleen, 1.4 per cent of the injected dose. 5. Approximately 20 per cent of the injected peroxidase was excreted in the urine during the first 6 hours, and the concentration of peroxidase in blood serum and urine fell exponentially during this time. After 6 hours, only low concentrations were excreted in the urine but low enzyme activity was still detectable after 30 hours. Approximately 6 per cent of the injected dose was excreted in the feces from 6 to 20 hours after administration. 6. After feeding through a stomach tube, low concentrations of peroxidase were found in blood serum and urine. Considerable variations in the extent of absorption from the gastrointestinal tract were observed in individual rats.     

The absorption of ingested neptunium, plutonium and americium in newborn hamsters

Hamsters aged 1, 4, 7, 22 and 30 days were given oral doses of either plutonium-239 citrate or americium-241 nitrate. The values of gastrointestinal absorption obtained were 3.5, 1.4, 0.04, 0.007 and 0.003 per cent, respectively, for plutonium and 4.5, 1.7, 0.5, 0.006 and 0.02 per cent, respectively, for americium, compared with values in adults of 0.01 per cent for plutonium and 0.05 per cent for americium. The absorption of neptunium was measured in hamsters aged 2 and 4 days and values of 2.3 and 1.7 per cent, respectively, were obtained for 239Np as the nitrate and 5.5 and 2.1 per cent, respectively, for 239Np as the bicarbonate compared with the values in adults of 0.02 per cent for both chemical forms. Thus, the absorption of plutonium, americium and neptunium at 1-2 days of age was about 100 times greater than in adults. The results for plutonium and americium show that absorption decreased rapidly with age over the suckling period. The values of absorption obtained at the time of weaning at 22 days were lower than in adults.     

Antibacterial prophylaxis of bacteriuria at transrectal multifocal prostatic biopsy]

It was shown that prophylactic use of ciprofloxacin (500 mg per os 30 min prior to and 5 days after transrectal multifocal prostatic biopsy) along with topical treatment with 40 ml 1% povidone-iodine and evacuant enema provided negative bacteriological urine analysis in 24 hours for 94.4 per cent of cases. Positive effect was registered for all patients as no urinary tract infections were demonstrated. Transitory fever over 37.5 degrees C was not registered at 67 (97.2 per cent) patients, for the rest cases no changes of the treatment regime were necessary. The results of the trial proves high bacteriological and clinical efficacy of the therapy regimes and allow to recommend its implementation at transrectal biopsy.     

The protective effect of zinc sulphate pretreatment against duodenal ulcers in the rat

Exogenously administered zinc compounds have been shown to possess antiulcer activity in the development of gastric lesions. The aim of this study was to investigate the effects of zinc sulphate pretreatment of rats on cysteamine-induced duodenal ulcers and to correlate them with changes in zinc serum and tissue levels. Atomic absorption spectrophotometry was used to determine zinc serum and tissue concentrations in all animal groups. Cysteamine produced marked duodenal ulceration in control animals 24 h after application, with an increase in endogenous zinc tissue concentrations and a marked decrease in serum concentrations. Zinc sulphate (20, 40 or 80 mg kg-1) applied per os one hour prior to cysteamine application inhibited the development of duodenal lesions in a dose-related manner. The application of zinc sulphate in a single intraperitoneal (i.p.) application (80 mg kg-1) did not, however, prevent the formation of duodenal lesions. In order to assess zinc absorption from the gastrointestinal tract, one group of rats received a single oral dose of zinc sulphate (80 mg kg) without cysteamine application. The observations of this study seem to indicate that zinc plays an important cytoprotective role in duodenal ulcer disease.     

Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds

In the pharmaceutical industry, orally active compounds are required to have sufficient water solubility to enable dissolution within the gastrointestinal tract prior to absorption. Limited dissolution within the gastrointestinal tract often reduces the bioavailability of hydrophobic drugs. To improve gastrointestinal tract dissolution, nonaqueous solvents are often used in the form of emulsions and microemulsions. Here, we show that oil-free polyelectrolyte nanosystems (micellar dispersions and 100-300 nm particles) prepared from poly(ethylenimines) derivatized with cetyl chains and quaternary ammonium groups are able to encapsulate high levels of hydrophobic drug (0.20 g of drug per g of polymer) for over 9 months, as demonstrated using cyclosporine A (log P = 4.3). The polyelectrolytes facilitate the absorption of hydrophobic drugs within the gastrointestinal tract by promoting drug dissolution and by a hypothesized mechanism involving paracellular drug transport. Polyelectrolyte nanoparticle drug blood levels are similar to those obtained with commercial microemulsion formulations. The polyelectrolytes do not promote absorption by inhibition of the P-glycoprotein efflux pump.     

Radiographic Diagnosis of Intestinal Perforation in Early Infancy

Records of 25 patients with intestinal perforation in early infancy who were treated at the Los Angeles County General Hospital in a period of 15 years were reviewed. Sixteen had roentgen evidence of pneumoperitoneum, and nine did not. The mortality rate was 94 per cent in the group with pneumoperitoneum, 78 per cent in the other, and 88 per cent overall. Multiple sites in the gastrointestinal tract were involved, and the causes of the lesions were diverse and frequently obscure. Prematurity, obstetrical and iatrogenic complications, and congenital anomalies were factors often associated with intestinal perforation. Roentgen features appeared to offer the best hope for diagnosis and appropriate treatment.     

CIRRHOSIS OF THE LIVER—Clinical Course in 2,377 Patients at San Francisco General Hospital

The records of 2,377 patients with Laennec''s cirrhosis were reviewed for the period 1947-1957. The chief presenting symptom was ascites in 46 per cent, bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both jaundice and ascites in 4 per cent. Nearly half of the patients died during the period under study—one-third from hepatic failure, one-third from gastrointestinal bleeding, and one-third from other causes, most of which were related to alcoholism.Massive gastrointestinal bleeding occurred in 21 per cent of the patients at some time in their clinical course, and in the 10 per cent of these in whom ulcer was demonstrated, one-fifth died as a result of the hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per cent of all those who bled from varices were dead at the end of one year, and 91 per cent were dead at the end of three years.The survival curve of a group of patients who bled once and were good operative risks but had received no operative treatment was compared to the survival curve for entire group who survived the first hemorrhage. The three-year survival in the good risk group was 47 per cent; for the group as a whole it was 30 per cent. The difference in mortality rate was primarily due to an increased number of deaths from hepatic failure in the combined group, whereas 60 per cent of the good risk group died of recurrent gastrointestinal hemorrhage.As 86 per cent of those who were to die of gastrointestinal bleeding did so at the first hemorrhage, it was concluded that any decided improvement in the salvage rate achievable by operation must come from some means of diagnostic forecast of the likelihood of bleeding, with resort to prophylactic operation in such cases.     

The structure and antibiotic sensitivity of the causative agents of community-acquired infectious diseases of bacterial origin in children]

Four hundred and forty pediatric patients at the age of 7 days to 15 years with various infections admitted to the Hospital within a month were examined. The biological material was inoculated to blood agar on the first days of the patient admittance to the Hospital and after the growth the organisms were isolated and identified. Antibiotic susceptibility of the isolates was assayed with the disk diffusion method. 479 strains in all were tested. The most frequent cases requiring hospitalization and antibiotic therapy were those of respiratory tract infections (54.09 per cent), urinary tract infections (26.36 per cent), cutaneous and subcutaneous fat diseases, gastrointestinal diseases and others (about 25 per cent of the cases in all). The main pathogens were Streptococcus viridans, S.aureus and S.epidermidis, as well as Enterobacteriaceae (chiefly E.coli) whose frequencies were practically equal (in 25-35 per cent of the cases). The Pneumococcus isolates amounted to 6.3 per cent. Nonfermenting bacteria (Pseudomonas aeruginosa and Acinetobacter) and some representatives of Enterobacteriaceae (Citrobacter, Serratia, Morganella) were isolated from 7 per cent of the patients. The frequency of Klebsiella and Enterobacter was about 11 per cent. The main pathogens were tested for their susceptibility to amoxycillin/clavulanic acid, ampicillin, oxacillin and gentamicin. The least active antibiotic was ampicillin. 88.8 per cent of the E.coli isolates and 100 per cent of the Klebsiella, P.mirabilis, Morganella, Citrobacter, Enterobacter and Serratia isolates were resistant to it. 53.2 per cent of the Streptococcus isolates including 64.5 per cent of the Pneumococcus isolates were as well resistant to ampicillin. 59.5 per cent of the Streptococcus isolates (mainly S.viridans and Enterococcus) was susceptible to oxacillin, 22.2 per cent of them being moderately susceptible. 62.5 per cent of the Pneumococcus isolates and 78.1 per cent of the Staphylococcus isolates were also susceptible to oxacillin. The highest susceptibility of the isolates was that to amoxycillin/clavulanic acid, i.e. 90.1 per cent of the strains, 79.9 per cent of them being highly susceptible. All the isolates of Citrobacter, Serratia and Morganella and some isolates of P.aeruginosa, Acinetobacter, Enterobacter, Klebsiella and E.coli were resistant to amoxycillin/clavulanic acid. As for the latter 5 organisms their susceptibility to amoxycillin/clavulanic acid was comparable with that to gentamicin. The susceptibility of the Streptococcus and Staphylococcus isolates to amoxycillin/clavulanic acid was significantly much higher than that to oxacillin, gentamicin and ampicillin: 93 per cent of the Streptococcus isolates (62.7 per cent of the Pneumococcus isolates) and 90.7 per cent of the Staphylococcus isolates.     

The Role of the Gut in Albumin Catabolism : II. Studies in enterectomized rabbits

Using I¹³¹-albumin tracer methods, albumin breakdown rates were estimated in 7 rabbits following extensive gastrointestinal resection, including 5 with nearly complete enterectomy, 1 with total gastroenterectomy, and 1 with gastrectomy only, and in 4 sham operated rabbits. Breakdown rates in the resected animals varied from 48 to 187 per cent of the corresponding controls, with an average of 96 per cent. It is concluded that no more than one-half, and probably much less, of albumin breakdown occurs in the gastrointestinal tract.     

Primary carcinoma of the gallbladder; review of 173 cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females. Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease. All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy. The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred. Gallstones were found in 79.8 per cent of the cases.     

Poikilocytosis in Cancer Patients

The incidence of poikilocytosis in 100 patients with cancer of various organ systems was found to be 12 per cent. Poikilocytosis was more frequently seen in patients with adenocarcinoma of the gastrointestinal tract and with inoperable metastatic carcinoma than in patients with other malignant lesions. Anemia was associated in three cases, but in nine instances the patient was not significantly anemic at admission. Two of these patients may have been dehydrated. Uremia was not a factor in any of the cases.Fifty per cent of the patients exhibiting poikilocytosis died or were in a terminal condition within one month after the observation was made, as compared with 21 per cent of the patients who did not have evidence of poikilocytosis. These findings show that poikilocytosis may occur in cancer patients without anemia or uremia; and they indicate that its presence is an unfavorable prognosis sign.     

Gastrointestinal stability and absorption of insulin in suckling pigs

Stability and absorption of orally administered fluorescein-isothiocyanate labeled insulin (FITC-insulin) in the gastrointestinal (GI) tract were investigated in newborn and 3-day-old pigs. The uptake of FITC-insulin by the intestinal epithelial cells was visualized using confocal laser scanning microscopy. Following oral administration, 3 h later 56 and 88% of orally administered fluorescence was found in the GI tract in newborn and 3-day-old piglets, respectively. Chromatographic analysis revealed that 15-37% of fluorescence recovered from the gastric and proximal intestinal contents was eluted in the void volume of a Sephadex G-25 column. It was also observed that oral administration of FITC-insulin at a dose of 100 nmol/kg body weight led to a significant decrease in blood glucose in newborn pigs (P<0. 05) but not in 3-day-old pigs. Microscopic examination showed that FITC-insulin was taken up via the vesicular transport mechanism throughout the whole small intestine but the ileum appeared to be a preferred site for FITC-insulin transport in newborn pigs. In 3-day-old pigs, the uptake of FITC-insulin occurred only in the distal part of the small intestine. These findings suggest that milk-borne insulin may partially survive in the GI lumen and subsequently act on the gastrointestinal tract in suckling piglets, while GI absorption of milk-borne insulin is limited to newborn pigs.     

Absorption and excretion of tablet disintegrating β-cyclodextrin polymer in rats

Absorption and excretion of a new tablet disintegrating agent, a crosslinked β-cyclodextrin polymer was investigated following per os administration in the rat. The polymer, which is insoluble but swells in water, was prepared from β-cyclodextrin by reacting with [2-¹⁴C]epichlorohydrin in an alkaline medium. Radioactivity of blood, urine, faeces, exhaled carbon dioxide and the gastrointestinal tract was determined by a liquid scintillation method. No radioactivity could be detected in the blood up to 24 h after the administration of the polymer. Radioactivity of urine and exhaled carbon dioxide together did not exceed 0·11% of the total administered radioactivity, 98% of which was found in the large intestine and the faeces. Therefore, it is assumed that β-cyclodextrin polymer could not be absorbed from the gastrointestinal tract.     

Intestinal bacterial population of healthy rats during the administration of chitosan and chitooligosaccharides

The effect of the administration of chitosan (CS) and chitooligosaccharides (COS) on rat fecal microbiota was analyzed in this study. The profile of total bacterial population was monitored during 3 weeks of CS or COS application using denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons. Quantitative PCR was used for monitoring possible changes in the levels of total bacteria and the levels of individual bacterial groups: Bifidobacteria, Clostridium leptum, Enterobacteriaceae, Lactobacillus–Streptococcus–Enterobacter, and Bacteroides–Prevotella. The DGGE profiles revealed a high complexity and individuality of each tested subject, and variations in the composition of band pattern were observed. CS or COS per os administration changed the profile and structure of the microbial ecosystem of the gastrointestinal tract of healthy rats. COS have, in most cases, an opposite effect compared with CS; only the Bacteroides–Prevotella bacterial group and Enterobacteriaceae were influenced in the same way. The Bifidobacteria group was not influenced by the administration CS and COS.