Biomedical subjects

R Henriksson

Publications and source records attributed to R Henriksson.

At least 91 records · Page 5Linked to original sources

PubMed1995

Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation.

PURPOSE: The expression of different neuropeptides in the innervation of submandibular and parotid glands of the rats was examined 2 and 5 days after initiation of radiation treatment as well as 10 and 180 days following the termination of irradiation. METHODS AND MATERIALS: The irradiation was given on 2 or 5 consecutive days with daily doses of 4-8 Gy up to a total dose of 20-40 Gy. Immunohistochemical methods were used for the demonstration of substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and, the rate-limiting enzyme in the catecholamine synthetic pathway, tyrosine hydroxylase (TH). The content of SP was also analyzed by the use of radioimmunoassay (RIA). RESULTS: In the parenchyma of both the submandibular and the parotid glands of control animals as well as after 2 days of irradiation treatment, a few nerve fibers showing SP-like immunoreactivity (LI) were observed. A marked increase in the expression of SP in the innervation of the parenchyma in both glands was observed 10 days after cessation of radiation treatment. The number of stained nerve fibers and the intensity of fluorescence in the fibers seemed to be dose dependent because the group subjected to a total dose of 40 Gy displayed a more pronounced staining intensity than that treated with 30 Gy. These results were supported by the RIA analysis. One hundred eighty days after treatment no obvious differences in SP-expression were seen between control and irradiated animals. No acute and long-term alterations were seen with regard to the other peptides and TH. CONCLUSIONS: These results suggest that specific dose- and time-dependent changes in the expression of SP in the parenchyma of both submandibular and parotid glands occur in response to fractionated irradiation. The observations add further aspects to the tissue differences in physiological response and sensitivity to irradiation.

Animals↗

PubMed1995

Bombesin-like immunoreactivity in the rat larynx: increase in response to irradiation.

It is previously well known that bombesin has effects as growth factor and that changes in bombesin content in air-way structures occur in various patho-physiological conditions. In the present study, the effects of radiotherapy on bombesin expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 gray daily. Ten days after cessation of irradiation, the subglottic part of the larynx from irradiated and control animals was dissected out, and processed for immunohistochemistry or radioimmunoassay. The radioimmunoassay analysis showed that the content of bombesin-like material increased 2-fold after irradiation. The immunohistochemical analysis displayed an increased bombesin-like immunoreactivity in local ganglionic cells and in nerve fibers in the submucosal glands. These nerve fibers are likely to be derived from the local ganglionic cells. On the other hand, there was no change in the pattern of immuno-reactivity in the innervation of the epithelium and the lamina propria, including the blood vessels. The observations show that radiotherapy can be added to the list of factors that influence bombesin expression in airway structures.

Animals↗

PubMed1995

Effects of estrogens and progestogens on the membrane permeability and growth of human prostatic carcinoma cells (PC-3) in vitro.

The effects of estrogens and progestogens in the management of prostatic adenocarcinoma are generally believed to be related to their suppressive effect on the hypothalamic-pituitary-testicular axis, but other mechanisms have also been suggested. The present study was designed to investigate if an androgen-insensitive human prostatic cancer cell line (PC-3) is sensitive to estrogens or progestogens and to elucidate possible mechanisms of action. Both estrogens and progestogens in high doses (10(-5) M) suppressed tumor cell growth. At these high doses medroxyprogesterone acetate (MPA) most effectively reduced the uptake of 86rubidium chloride, indicating the strongest effect on ion transport and membrane permeability. Effects on rubidium transport were also seen after estrogen treatment. It is suggested that estrogens and progestogens have direct cytotoxic effects on prostatic carcinoma cells in vitro, possibly by an effect on the cell membrane.

Adenocarcinoma↗

PubMed1995

Irradiation influences the expression of substance P and enkephalin in the rat larynx.

The effects of radiotherapy on neuropeptide expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 Gray daily. Ten days after the end of irradiation, the larynx, the laryngeal nerves and different ganglia related to the larynx were dissected out from irradiated and control animals and processed for neuropeptide immunohistochemistry. There was an increased immunolabelling for two of the neuropeptides tested, substance P and enkephalin, in the innervation of the subglottic glands and in the acetylcholinesterase-positive ganglionic cells of the local ganglia. These cells were interpreted as representing postganglionic parasympathetic ganglionic cells. The changes seen in the subglottic glands were interpreted as most likely being related to the changing pattern of staining seen in the local ganglia. No changes in substance P- and enkephalin expression were observed in other laryngeal structures, the nodose ganglia, superior cervical ganglia or laryngeal nerve paraganglia. Thus, in certain respects neuropeptide expression in the larynx is modulated by radiotherapy. Since neuropeptides have both neurotransmitter and/or neuromodulator effects in airway tissue and since they show effects as growth factors, the occurrence of this plasticity in neuropeptide expression should be taken into consideration in future studies examining the effects of irradiation on normal/diseased airway tissues.

Animals↗

PubMed1995

Effects of active addition of bacterial cultures in fermented milk to patients with chronic bowel discomfort following irradiation.

Radiotherapy is a cornerstone in the treatment of malignancies in the pelvis. Consequently, there is usually exposure of the intestine and especially the lower colon and rectum, with ensuing disturbances in bowel habits at different times following radiotherapy. The main problem is diarrhoea associated with lactose intolerance, bile salt absorption and fat malabsorption. Bacterial contamination has also been described. In the present study we have evaluated the influence of the active administration of specific bacterial cultures in fermented milk, which inhibit the growth of potentially pathogenic micro-organisms, to 40 consecutive patients with chronic alteration in their bowel habits caused by previous radiotherapy of pelvic malignancies. The results suggest that intake of fermented milk products could be of value in decreasing chronic bowel discomfort following radiotherapy of pelvic malignancies. However, a more extensive study is warranted in order to very the significance of the results and to find the optimal product.

Animals↗

PubMed1995

Long-term memory deficits in patients with malignant gliomas.

Knowledge about the neuropsychological performance of adult patients with brain tumors, and especially with malignant gliomas, is limited. In this study 30 patients were consecutively included at time of diagnosis. Five months after completion of radiotherapy eleven of the patients showed no signs of focal neurology or tumor recurrence. These eleven patients, and their partners, were interviewed independently. Using each partner as control the patients were assessed neuropsychologically with special emphasis on memory abilities. The selective reminding technique was used with nouns of different visual imagery. A consistent pattern was found: there was no clear impairment in global intellectual abilities, but there was a pronounced deficit in long-term memory. However, the patients had a preserved capacity to use visual imagery to boost performance. It is important that medical staff acknowledge or confirm this problem. The sparing of imaginal coding makes it possible for the staff to assist with advice facilitating memory. Memory is a vital cognitive ability and the selective reminding technique was a sensitive method capable of detecting subtle impairments. The technique is recommended in future examinations of conditions and evaluations of treatments affecting the CNS.

Adult↗

PubMed1995

Radiosensitizing effect of estramustine in malignant glioma in vitro and in vivo.

Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17 beta-estradiol, has been demonstrated to exert specific antiproliferative effects on human glioma cells in vitro. The cytotoxic effect is, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG, in vitro, and in the rat glioma BT4C in vitro and in vivo. In all cell-lines an additive effect of EMP and radiation was obtained in vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill will be increased from 2-3 to 5-10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was found to be synergistic. Flow cytometry demonstrated an arrest in G2/M phase in all cell-lines after EMP treatment. This block in G2/M phase in addition to the previously demonstrated induction of free oxygen radicals, and the increase of blood flow with an assumed subsequent increase of oxygenation, might provide an explanation for the observed radiosensitizing effect of estramustine.

Animals↗

PubMed1995

Can alpha-tocopherol and beta-carotene supplementation reduce adverse radiation effects on salivary glands?

In this study, we evaluated whether supplementation with antioxidant vitamins can reduce the adverse effects of irradiation on the salivary glands in the rat. Four groups of adult Sprague-Dawley rats were given a basic diet providing 0.6 mg alpha-tocopherol and no beta-carotene per day. In two groups the basic diet was supplemented with 3.4 mg alpha-tocopherol and 6 mg beta-carotene per day from 14 days before irradiation until 12 days after completed irradiation. One group of rats given basic diet and one group given supplemented diet were irradiated with 7 Gy daily for five consecutive days. Isoproterenol and pilocarpine-stimulated whole saliva was collected from all rats 2, 4 and 26 weeks after irradiation. Vitamin-supplemented irradiated rats had higher secretion rates on all three occasions compared with those of irradiated rats given basic diet. The changes in saliva composition seen in irradiated rats were less accentuated in vitamin-supplemented, irradiated rats. The proportions of acinar cells were significantly decreased both in parotid and submandibular glands 26 weeks after irradiation. Supplementation with alpha-tocopherol and beta-carotene did not alter the morphology of the glands.

Animals↗

PubMed1995

Effects of intrapleural mitoxantrone and mepacrine on malignant pleural effusion--a randomised study.

30 patients with malignant pleuritis were randomised to be treated, either with intrapleural instillation of mepacrine chloride or with mitoxantrone. The patients were evaluated with chest X-ray and a symptom questionnaire during a follow-up period of 12 weeks. Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients. High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low, giving a plasma/intracavity ratio generally of less than 1:60. The chest X-rays showed excellent results for both treatment modalities. However, the patients treated with mepacrine chloride experienced greater discomfort with fever and pain, and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks. We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion. However, mitoxantrone seems to have further advantages when it comes to improving the quality of life.

Adult↗

PubMed1995

DNA fragmentation induced by the antimitotic drug estramustine in malignant rat glioma but not in normal brain--suggesting an apoptotic cell death.

Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has been shown to be metabolised and to induce specific antiproliferative effects in malignant glioma, including arrest of glioma cells in the G2/M phase of the cell cycle, damage to cell membranes and DNA and induction of free oxygen radicals. To evaluate further the effects of estramustine, an in vivo rat glioma model using inbred BD-IX rats and the BT4C cell line was set up. In order to detect cells with fragmented DNA, tumour and brain specimens were, following fixation for histological examination, processed for in situ end labelling (ISEL) with biotin-labelled nucleotides. Fresh tissue fragments were also used for DNA integrity analysis on agarose gels. It was demonstrated that estramustine induced clusters of ISEL-positive cells and a pronounced typical fragmentation of DNA 0.5-8 h after treatment. In tumours examined 24 or 94 h after estramustine treatment, and in untreated tumours, only occasional single ISEL-positive cells were scattered in the tumour. DNA from normal brain tissue did not display any visible sign of fragmentation. These changes are indicative of programmed cell death induced by estramustine in glioma cells but not in normal brain tissue. Further studies are, however, needed to establish in detail the mechanism of cell death following treatment with the antimitotic drug estramustine.

Animals↗

PubMed1995

Metoclopramide inhibits the cytotoxicity of cisplatin and enhances the cytotoxicity of epirubicin.

During cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting by antineoplastic drugs. Some antiemetics have however been afflicted with cytotoxic effects during f1p4otherapy. The influence of the commonly used antiemetic metoclopramide on the cytotoxicity of epirubicin and cisplatin was tested on fibroblasts (V79) and lung cancer cells (P31) in vitro. The clonogenic survival of fibroblast and lung cancer cells were reduced when the cells were exposed to epirubicin or cisplatin. Metoclopramide (0.5 or 5 mg/l) enhanced epirubicin-induced toxicity to both fibroblast and lung cancer cells, but inhibited the cytotoxicity of cisplatin. The demonstrated effect of metoclopramide on cells in vitro and the fact that metoclopramide is used as a routine antiemetic during cancer treatment, may indicate that a possible clinical interaction with the antineoplastic action of cancer treatment drugs should be given attention.

Animals↗

PubMed1995

Effects of IL-2 treatment on different compartments of the irradiated rat lung analysed by bronchoalveolar lavage and lung tissue morphology.

In recent years, interleukin-2 (IL-2) has been used as an immunomodulatory agent in the treatment of various malignant tumours. However, this treatment has been limited by serious side-effects, including toxic reactions in the lung. The effects of IL-2 treatment on inflammatory cell populations in the normal and irradiated rat lung were investigated in this study. IL-2 was continuously administered as a subcutaneous infusion over a 6 week study period. Irradiation was given in a single dose (25 Gy) the day after starting IL-2 treatment. Evaluation with bronchoalveolar lavage fluid (BALF) analysis and lung tissue morphology was made 6 weeks after irradiation. In nonirradiated rats, IL-2 treatment induced significant increases in the total number of inflammatory cells in the perivascular, interstitial and peribronchial tissues as well as in the alveolar space. These increases were not reflected in BALF; on the contrary, a significant decrease of the total numbers of inflammatory cells was found in BALF. Irradiation alone caused a more pronounced inflammatory response was significant increases of all inflammatory cells in all lung compartments, which was also reflected in BALF. Concomitant treatment with IL-2 and irradiation induced an enhanced accumulation of inflammatory cells in the perivascular and peribronchial tissues compared with irradiation alone. Thus, both irradiation and IL-2 treatment induce inflammatory reactions in the lung, but there were signs of synergistic effects seen in this study. Furthermore, the results also emphasize the difficulties in making sophisticated conclusions from BALF analyses alone.

Animals↗

PubMed1995

Sucralfate: prophylaxis of mucosal damage during cancer therapy.

BACKGROUND: Chemotherapy and radiotherapy of different malignancies may be complicated by a variety of side effects, some of which may be related mucosal damage. RESULTS: There is increasing evidence that sucralfate reduces the severity of radiation-induced mucositis in the head and neck, esophagus, and the lower gastrointestinal tract. Sucralfate also seems to protect the skin during radiotherapy and to reduce chemotherapy-induced mucositis. CONCLUSION: Further studies could be of interest to define the clinical significance of sucralfate in reducing the mucosal damage and increasing quality of life during an following cancer therapy.

Anti-Ulcer Agents↗

PubMed1995

Regeneration of parotid acinar cells after high radiation doses. A morphological study in rat.

The acute and late effects of fractionated irradiation on rat parotid gland acinar cells were studied by light and electron microscopy. At 10 days after the last irradiation session (6 Gy or 9 Gy daily during five consecutive days) no effects were seen. At 180 days, minor loss of acini was detectable after a total dose of 30 Gy. After 45 Gy a massive acinar loss was seen at that time; the number of acini had diminished and minor duct-like structures and scattered amounts of fibrous stroma dominated the slides. The remaining acini were disorganized and usually larger compared with the control side and to non-irradiated animals. The acinar cells appeared larger than in the controls. The ducts were better preserved but the intercalated ducts often seemed to be larger than normal. We suggest that this phenomenon indicates a remaining capacity of the parotid gland to regenerate acinar cells even after high radiation doses.

Animals↗

PubMed1995

Effects of sucralfate on mucositis during and following radiotherapy of malignancies in the head and neck region. A double-blind placebo-controlled study.

Radiotherapy of head and neck malignancies is accompanied by oral discomforts, such as epithelitis, pain and functional impairment. This can lead to chronic sequalae with subjective distress such as loss of taste and xerostomia and pronounced decrease in quality of life. Thus, the need to reduce the mucosal damage following radiotherapy is obvious. Therefore, we investigated the possible ability of sucralfate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, in preventing oral discomfort in patients treated with curative intent for malignancies in the head and neck region. The study was double-blind, placebo-controlled and randomized and included 50 consecutive patients. The study demonstrated that the proportion of patients with severe mucosal reactions was significantly lower in the sucralfate group than in the placebo group.

Combined Modality Therapy↗

PubMed1995

Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro.

At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, as far as we know, not been studied in this respect. In the present study, the effects of the 5-HT3 receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10(-5) mol/l) had no effect on the survival of irradiated cells. Granisetron (10(-5) mol/l) significantly potentiated cytotoxicity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10(-7) mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT3 receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment.

Animals↗

PubMed1994

Estramustine-binding protein and specific binding of the anti-mitotic compound estramustine in astrocytoma.

Estramustine-binding protein (EMBP) is a M(r) 46,000 heterodimeric protein originally isolated from prostatic tissue. It has a demonstrated high affinity for, and selective binding of, estramustine, which is a derivative of 17 beta-estradiol and nornitrogen mustard with antimitotic activity. In this study, we have analysed the expression of an EMBP-like protein in astrocytoma specimens. Immunohistochemistry revealed a pronounced reactivity for EMBP in astrocytoma grades III-IV as well as in metastatic prostatic adenocarcinoma used as positive control. In astrocytoma grades I-II, the expression was weak. The EMBP-like protein was quantified by radioimmunoassay in astrocytoma tumor tissue with higher concentrations in malignant astrocytoma, grades III-IV, compared to grades I-II tumors. Western immunoblotting of immunoaffinity purified EMBP-like protein under nonreducing conditions revealed an immunoreactivity corresponding to M(r) 138,000 and 200,000, indicating a different structure of EMBP in astrocytoma compared to prostatic tissue. Specific binding and the presence of saturable binding sites for 3H-labeled estramustine were demonstrated in astrocytoma tissues expressing EMBP-like protein. Scatchard plot analysis showed a Kd at approximately 30 nM, which suggests a binding affinity for estramustine in the same range as previously reported for EMBP in the prostate. Moreover, the number of estramustine binding sites/g tumor as calculated from the Scatchard plots was well correlated with the EMBP levels determined in the radioimmunoassay. In conclusion, an EMBP-like protein is expressed in astrocytoma. This protein may be responsible for the specific binding of estramustine in the tumor tissue. Whether this specific binding of estramustine is of importance for the cytotoxic effect in glioma cells remains to be evaluated.

Astrocytoma↗

PubMed1994

Estramustine potentiates the effects of irradiation on the Dunning (R3327) rat prostatic adenocarcinoma.

The present study was designed to determine if estramustine phosphate (EMP) could potentiate the effects of irradiation on the Dunning (R3327) prostatic adenocarcinoma in rats. Two groups of male Copenhagen x Fisher F1 rats carrying bilateral tumors in the flank were used. Irradiation was given with a linear accelerator 6 MV, in a dose of 6 Gy/day for 4 days to the tumor on one side while the tumor on the other side served as control. EMP (360 micrograms/24 hours) was administered with osmotic pumps to one group of rats for 2 weeks, starting 1 week before irradiation. Tumor growth was calculated by measuring tumor volume, and tumor blood flow was measured 8 weeks after treatment. Irradiation alone effectively delayed tumor growth and EMP enhanced these effects. Tumor blood flow was stimulated by EMP treatment irrespective of radiotherapy. Volume density of tumor epithelium was effectively decreased by irradiation but no significant effects could be seen after EMP. In conclusion, the present study shows that EMP potentiates irradiation on rat prostatic adenocarcinoma, and further evaluation of this therapeutic approach in the clinical treatment of prostatic carcinoma is thus justified.

Adenocarcinoma↗