Separate and simultaneous effects of ethanol, hypertonic saline and insulin on the function of the subcommissural organ.
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Animals↗
Biomedical subjects
L Karlsson
Publications and source records attributed to L Karlsson.
Functional status of the hypothalamo-neurohypophyseal system after two weeks' administration of adrenalin and insulin in rats under continuous influence of ethanol.
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Alcoholism↗
Caffeine exposure in utero increases the incidence of apnea in adult rats.
Caffeine abuse during pregnancy may be a factor in the development of long-term breathing abnormalities. Therefore, the objective of the present study was to monitor adult breathing patterns after in utero exposure to caffeine. This was done by isolating episodes of apnea of more than 6-s duration from the breathing data as obtained by the Cotwatch breathing monitors adapted for rat use. The breathing record obtained over 6 consecutive days was expressed as daily weighted apnea-hypopnea density (WAHD) values. It was shown that administration of caffeine in moderate (30 mg/kg daily) or high (60 mg/kg daily) doses throughout gestation resulted in a significant dose-dependent increase in the WAHD value. The experimental offspring were significantly growth retarded in utero and their subsequent growth rates were also affected. The caffeine-exposed pups grew more slowly with growth plateauing at the same age, resulting in smaller adults. A link was suggested between infants with apnea of prematurity, when occurring after the first week, and an increased risk for later apnea and sudden infant death syndrome.
Animals↗
Methodological studies of multiple reference genes as endogenous controls in vascular gene expression studies.
Detection and quantification of differentially expressed genes requires valid and reliable references to control for error variability introduced by preparatory procedures or efficiency of reverse transcription and polymerase chain reaction (PCR) amplification conditions. So-called housekeeping genes are frequently used as endogenous standards, based on the assumption that they are constitutively expressed and independent of experimental conditions. However, if the influence of experimental stimuli is to be analyzed, it cannot a priori be assumed that their expression is unaffected by stimulation. In the present study, the authors studied the expression of different housekeeping genes in the vascular endothelium of intact conduit vessels perfused in a unique biomechanical perfusion model. Ten control gene candidates were investigated by microarray expression analysis. Further, five of these genes were systematically analyzed by real-time reverse transcriptase (RT)-PCR gene quantification and their suitability as reference genes were evaluated. On the basis of these findings, the authors suggest criteria for evaluation of endogenous control genes in vascular perfusion studies.
Biomedical Research↗
Laboratory evaluation of the TDx assay for detection of cannabinoids in urine from prison inmates.
The TDx (Abbott Laboratories) and the EMIT-Cobas (Syva Corp. & Roche) techniques for cannabinoid assay were evaluated. Authentic urine samples submitted for narcotics screening were analyzed for cannabinoids. All positive findings were confirmed by an HPLC procedure. The results indicated that the EMIT assay detects a few more positive samples, but also yields a higher rate of unconfirmed positive results compared to the TDx. Those additional "true" positives by EMIT had concentrations of the delta 9-THC-11-carboxylic acid below 10 ng/mL.
Cannabinoids↗
Determination of delta 9-tetrahydrocannabinol-11-oic acid in urine as its pentafluoropropyl-pentafluoropropionyl derivative by GC/MS utilizing negative ion chemical ionization.
A rapid and sensitive GC/MS method for the determination of delta 9-tetrahydrocannabinol-11-oic acid in urine is presented. Enzymically hydrolyzed urine was extracted with hexane/ethyl ether followed by a one-step derivatization procedure with a mixture of pentafluoropropionic anhydride and pentafluoropropanol. By using negative ion chemical ionization and selected ion monitoring, a 200-fold higher detectability was observed, compared with El or positive ion chemical ionization under the conditions used. Samples were analyzed with split injection on a fused silica capillary column with a total analysis time of less than four minutes. A deuterium labelled analogue was used as internal standard and the precision for the overall method was measured to 3.4% for a sample concentration of 230 ng/mL, and to 6.7% for 3 ng/mL. The minimum detectable amount was below 1 ng/mL.
Chemical Phenomena↗
Vertebral ring apophysis injury in athletes. Is the etiology different in the thoracic and lumbar spine?
In a radiologic study of the thoracolumbar spine in 143 athletes aged 14 to 25 years and 30 male nonathletes aged 19 to 25 years, abnormalities of the vertebral ring apophyses were analyzed. Abnormalities affecting the anterior part of the vertebral ring apophysis occurred exclusively in athletes and they were most common in wrestlers and female gymnasts. Different types of abnormalities were found and the type of abnormality was related to the spinal level. We propose that this is related to trauma of various types. Excavation of the anterior part of the vertebra, probably from compression forces, was mainly found in the thoracic and thoracolumbar junction of the spine. Persisting or enlarged apophysis, probably caused by avulsion of the anterior part of the vertebral ring apophysis, was only found in the lumbar spine.
Adolescent↗
Influence of a prostaglandin synthesis inhibitor and of thrombocytopenia on tumor blood flow and tumor vascular permeability. Experimental studies in the rat.
The intratumor distribution of vascular permeability in two transplantable rat tumors was studied by calculating tissue-plasma ratios of two intravenously injected labeled albumins with an interval of five hours between albumin injections. The data were calculated and presented as the capillary permeability surface area product (PS) in multiple tumor biopsies. Furthermore, the intratumor distribution of blood flow was studied by the intratumor uptake of intravenously injected 86Rb. The same parameters were also studied in normal striated muscle. Prolonged administration of a prostaglandin synthesis inhibitor, diclofenac-sodium (Voltaren) changed significantly the tumor blood flow towards higher values. A similar change was observed in animals with induced thrombocytopenia. Tumor PS values were increased by administration of diclofenac-sodium, but not by induced thrombocytopenia. The intratumor distribution of plasma volume, calculated from tissue-plasma values of albumin injected 5 minutes before the animals were killed, was not significantly changed as well as blood flow, plasma volume and PS in normal muscle. There was no significant correlation between separate tumor blood flow and PS values, while such a significant correlation was found in normal muscle. The observations made in this study suggest that a release of both prostaglandins and serotonin might be included in the regulation of tumor blood flow and vascular permeability.
Animals↗
Alprenolol as maintenance therapy for the protection against arrhythmia relapse in patients with DC-converted chronic atrial fibrillation.
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Adult↗
Influence of two prostaglandin synthesis inhibitors on the intratumor distribution of blood flow and vascular volume in a transplantable rat fibrosarcoma.
The intratumor and intramuscle distribution of blood flow and plasma volume was studied via isotope techniques in a transplantable rat fibrosarcoma. Administration of two prostaglandin synthesis inhibitors, indomethacin and diclofenac-sodium, had different effects. Indomethacin changed muscle plasma volume significantly towards higher values; a tendency to increased tumor plasma volume was also found. Diclofenac-sodium increased tumor blood flow, but had no significant influence on other parameters. These effects are discussed based on previous observations of reduction of tumor growth rate and tumor vascularization after administration of both drugs.
Animals↗
Estradiol regulates tumor growth by influencing p53 and bcl-2 expression in human endometrial adenocarcinomas grown in nude mice.
This study analyzes the effects of estradiol on p53 and bcl-2 expression, tumor growth and cell kinetic parameters in three human endometrial adenocarcinomas grown in nude mice. The tumors used were estradiol receptor (ER) positive but differed in receptor concentration and hormone sensitivity. All three tumors expressed wild-type p53 protein. Using a tumor with an estradiol independent but responsive (inhibited) growth phenotype, we found that an increase in the circulating estradiol concentration led to increases in p53 expression and a decrease in bcl-2 levels, resulting in increased cell loss (CL) measured as delayed tumor growth. In another tumor which demonstrated estradiol independent and resistant growth, we observed an estradiol dose-related increase in p53 expression but no changes in bcl-2 expression or cell kinetic parameters. The ER mechanism of these cells was at least partly intact, as evidenced by maintained PgR induction. The third tumor showed an estradiol independent and resistant growth phenotype and a non-functional ER mechanism, lacking PgR induction. After estradiol treatment of the tumor-bearing animals no changes were observed in p53 or bcl-2 expression or in cell kinetics. We conclude that estradiol may regulate tumor growth in some ER positive human endometrial adenocarcinomas through regulation of p53 expression, which in turn regulates the bcl-2 protein concentration. Furthermore, this regulation of p53 expression is estradiol dose dependent. These growth regulating functions appear to be strongly influenced by ER mechanisms and do not seem to operate synchronously in tumors with an estradiol resistant growth phenotype.
Animals↗
Characterisation of a human endometrial adenocarcinoma established in vivo and in vitro.
A moderately differentiated human endometrial adenocarcinoma was heterotransplanted into nude mice and later established as a continuous in vitro cell line. Western blot analysis showed an accumulation of p53 protein in the cell line compared to the original tumour and heterotransplants. Sequential analysis of the p53 gene revealed point mutations in codons 175 and 248 in the cell line while no mutations were found prior to in vitro establishment. Immunohistochemistry confirmed the epithelial origin of the heterotransplants and of retransplants of the cell line. The intraperitoneal retransplants remained moderately differentiated, whereas subcutaneous retransplants became less differentiated. Heterotransplants were estrogen receptor (ER) positive and progesterone receptor (PgR) negative, indicating preservation of normal steroid receptor status. The ER could not be detected in the in vitro cell line using an enzyme immunoassay, but was detected with Western blot using a polyclonal antibody toward the carboxy terminus. After estradiol treatment, the in vitro cell line became weakly positive for the PgR, suggesting the ER mechanism was at least partly intact. Tumour growth in vivo was independent of endogenous estrogen but was inhibited when the tumour-bearing animals were treated with estradiol. Analysis of cell growth kinetics by flow cytometry (FCM) after bromodeoxyuridine (BrdU)-labelling revealed no difference in S-phase fraction (SPF) or labelling index (LI) between the treated and control groups. Cell loss (CL) was significantly increased from 42% to 89%, resulting in increased tumour volume doubling time (TVDT). Under in vitro conditions estradiol treatment resulted in an increase in cell doubling time and this growth retardation was accompanied by a significant decrease in SPF and LI. The estrogen responsive (inhibited) phenotype was thus preserved in the in vitro cell line but was probably mediated through another mechanism. This cell line thus appears to represent the development of a more malignant clone with divergent receptor function and growth behaviour, and provides us with an interesting new tool for the study of tumorigenesis in the human endometrium.
Adenocarcinoma↗
Estradiol induces DNA fragmentation in a human endometrial adenocarcinoma with estradiol-inhibited growth phenotype.
A moderately differentiated human endometrial adenocarcinoma heterotransplanted into nude mice was investigated for morphological and molecular changes in the tumours after treating the animals with estradiol. The tumour growth was previously characterised as estradiol-independent but responsive (inhibited) without any changes in cell proliferation. In response to hormonal treatment rather the cell loss factor increased. In this experiment tumours influenced by estradiol were investigated at different time-points after treatment by an in situ labelling technique to detect cells undergoing DNA fragmentation as a sign of apoptosis. Expression of the apoptosis related protein bcl-2 was evaluated by Western blotting. Tumours from animals treated with estradiol showed an increase in tumour volume doubling time from 5.4 days to 16 days compared to control tumours. Histologically, tumours influenced by estradiol were better differentiated than control tumours and showed a significant increase in cells staining positively with the in situ apoptosis detection technique. A parallel time dependent decreased expression of bcl-2 protein was observed. These results confirm our previous findings where estradiol influenced the cell loss factor without changes in the growth fraction, indicating increased apoptotic activity in response to hormonal treatment.
Adenocarcinoma↗