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Biomedical subjects

R Henriksson

Publications and source records attributed to R Henriksson.

At least 163 records · Page 9Linked to original sources

Effects of chronic stimulation of salivary gland beta-adrenoceptors on saliva composition and caries development in the rat.

The effects of long-term beta-adrenoceptor stimulation or inhibition on parotid and submandibular glands, saliva secretion, and caries development were studied. Groups of rats were treated daily with: 0.5 or 5 mg/kg body weight of isoproterenol (IPR), 0.5 or 5 mg/kg bw propranolol (PRO), or saline. After 42 days, saliva was collected and analyzed for secretion rate, total protein, amylase, sialic acid and electrolytes. Total protein and amylase in saliva decreased and potassium increased in the high IPR group. Phosphate increased in both IPR groups and decreased in the high PRO group. The average weight of parotid glands increased 3.7 times in the high IPR group and 1.8 times in the low IPR group. Amylase and total protein in parotid gland extracts decreased in both IPR groups. The submandibular gland weight increased 1.5 times in the high IPR group. Total protein decreased in the high IPR group. There was no difference in caries development.

Amylases↗

Comparative study of demethoxydaunorubicin with other anthracyclines on generation of oxygen radicals and clonogenic survival of fibroblasts.

Demethoxydaunorubicin was compared to other anthracyclines (daunorubicin, doxorubicin, epirubicin) on its ability to generate free oxygen radicals when mixed with Fe2+ in solution and on its ability to reduce clonogenic survival of fibroblasts in culture. Oxygen electrode measurements of free radical generation showed that most of the consumed oxygen entered the monovalet oxygen reduction pathway. Catalase and superoxide dismutase additions inhibited oxygen consumption for all tested anthracyclines and diethylenetriaminepentacetic acid (DTPA) was also inhibitory except for demethoxydaunorubicin. Demethoxydaunorubicin and epirubicin dose-dependently reduced the clonogenic survival of fibroblasts. Addition of catalase or superoxide dismutase was without effect, whereas metal chelators DPTA, desferrioxamine and EDTA all protected against epirubicin-induced toxicity. Of the chelators, only desferrioxamine protected against demethoxydaunorubicin toxicity. Tests in vivo will further elucidate whether demethoxydaunorubicin also differs from the other anthracyclines in therapeutic effect as well as in side effects such as myocardial toxicity.

Animals↗

Interactions between anticancer drugs and other clinically used pharmaceuticals. A review.

Drug interactions are increasingly common, since clinical practice is getting more complex with the flood of new drugs. Simultaneously, the increased life expectancy of the population increases the number of individuals likely to receive multiple prescriptions. Cytotoxic drugs generally have a narrow therapeutic index, and are delivered at doses close to toxic levels. Consequently, a slight increase in biological activity caused by an interaction with other concomitantly administered drugs could be deleterious to the patient. Interactions between drugs can sometimes also be used in a positive way, i.e. to increase the therapeutic ratio and overcome drug resistance. Interactions between different cancer treatment modalities have attracted considerable interest. However, much less interest has been devoted to interactions between anticancer drugs and other pharmaceuticals. The purpose of this review is to summarize data about the interactions between anticancer drugs and other clinically used drugs with regard to effects on tumor and toxicity.

Analgesics↗

Protective effect of iron chelators on epirubicin-induced fibroblast toxicity.

Free oxygen radicals generated by anthracycline/iron complexes have been implicated in anthracycline cytotoxicity. We therefore tested whether enzymatic scavengers of free radicals or metal chelators were able to inhibit anthracycline toxicity. The survival of Chinese hamster fibroblasts was reduced when the cells were exposed to 0.1-1.0 mg/l 4'-epidoxorubicin (epirubicin). Superoxide dismutase (SOD) (250 mg/l), or catalase (250 mg/l) did not affect the clonogenic survival of the fibroblasts. The metal-chelators, diethylenetriamine-pentaacetic acid (DTPA) (100 mumol/l), EDTA (100 mumol/l), and desferrioxamine (100 mumol/l) all protected against epirubicin-induced clonogenic survival. The protection of chelators against epirubicin toxicity implies that chelators might also be able to modulate anthracycline toxicity in vivo.

Animals↗

Non-specific secretory supersensitivity in rat parotid gland following neonatal sympathetic denervation.

Newborn rats were surgically sympathectomized by extirpation of the left superior cervical ganglion. After 9 weeks the parotid glands of both sides were used for secretory studies. Isoprenaline, dopamine, and the dibutyryl analogue of cAMP (DBcAMP) caused an increase in amylase release, which was significantly higher in the denervated glands. Also carbamylcholine was more effective in the denervated gland; the concentration-response curve was shifted to the left, and the maximal output of amylase was increased. Neonatal sympathetic denervation induces supersensitivity for both adrenergic and cholinergic agonists as well as for DBcAMP. This may be due to compensatory mechanisms involving both up-regulation of receptors as well as amplification of the intracellular mediation.

Adrenergic Fibers↗

Characterization of dopamine-induced potassium efflux in rat parotid acinar cells.

The effects of dopamine and noradrenaline on potassium efflux from rat parotid gland were studied in a perifusion system. Tissue specimens were preincubated with 86RbCl and the efflux of 86Rb+ was used as a marker for potassium efflux. Noradrenaline induced 86Rb+ efflux more effectively than dopamine. The noradrenaline-induced efflux was inhibited by alpha-adrenoceptor blockers, especially the alpha 1-antagonist prazosin. The dopamine-induced 86Rb+ efflux was blocked by alpha-adrenoceptor antagonists, non-selective dopamine antagonists and a D-1 selective dopamine antagonist. The D-2 selective drug, sulpiride, did not affect the dopamine-induced 86Rb+ efflux. The dopamine effect was abolished when reserpinized animals were used, whereas the effect of noradrenaline was unaffected. The results suggest that dopamine has a presynaptic stimulatory effect in rat parotid gland, and that the presynaptic effect on potassium efflux seems to be mediated via the D-1 receptor subtype. Whether activation of the presynaptic D-1 receptors leads to noradrenaline release, or whether the D-1 receptor is coupled to the catecholamine transporter system remains to be studied further.

Adrenergic alpha-Antagonists↗

Estramustine inhibits monocyte phagocytosis.

Estramustine phosphate (EMP) influence on human monocyte phagocytosis of fluorescein isothiocyanate (FITC)-labeled yeast cells was measured in vitro. The method used, a modification of Hed's technique (FEMS Microbiol Lett 1:357, 1977), can differentiate between yeast cell engulfment and adherence to the phagocytotic cell surface. EMP is now accepted in the treatment of advanced prostatic carcinoma. In concentrations corresponding to the clinical situation (20-40 micrograms/ml), it dramatically inhibited the process of phagocytosis. The engulfment phase was inhibited, whereas cell adherence was less affected. This might be due to direct interaction with the microtubule system. The effects were totally reversible. In contrast, the metabolites estradiol and normustine did not affect engulfment of yeast cells, either as single agents or combined. The results demonstrate that the EMP complex caused an impaired phagocytosis, which could be of pathophysiological significance in the compromised cancer patients.

Cell Adhesion↗

Managing side-effects in radiotherapy with regard to the gastrointestinal tract.

Three different means of diminishing discomfort during radiation therapy of the gastrointestinal tract are demonstrated and discussed: 1. Use of the smallest possible treatment volumes in medically well developed regions with good possibilities for follow-up of all patients. 2. Regular consultations, with advice concerning food intake and dental hygiene 3. Use of the drug sucralfate, which may improve tolerance against the radiation-induced damage to the gastrointestinal mucosa.

Adult↗

Decreased peripheral beta-adrenergic reactivity in asthmatics treated with oral beta 2-agonists.

Peripheral beta-adrenoceptor reactivity, measured as the dermal erythematous reaction to iontophoretically administered isoprenaline was studied in 41 asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy control subjects. The response of intact superficial dermal blood vessels to isoprenaline, which has previously been demonstrated to be beta 2-adrenoceptor mediated, was reduced in asthmatics treated with high dose, oral, slow-release beta 2-agonists compared to healthy controls. The response in asthmatics not treated with oral beta 2-agonists and in patients with allergic rhinoconjunctivitis did not differ from controls. Thus, the peripheral beta 2-adrenergic reactivity of intact human superficial blood vessels is affected by oral, slow-release beta 2-agonists.

Administration, Inhalation↗

Glycoprotein tumour markers in head and neck neoplasms--a consecutive study on CA-50, CA 19-9, and CEA.

Serum levels of three glycoprotein tumour antigens (carcino-embryonic antigen, CEA; cancer-associated antigen 50, CA-50; gastrointestinal cancer-associated antigen, CA 19-9) were determined on 125 consecutive patients with tumours of the head and neck region. Elevated CEA values (greater than 5 units/ml) were found in 13/70 squamous cell carcinomas, 3/21 benign and 4/18 malignant salivary gland neoplasms. Elevated CA-50 values (greater than 17 units/ml) were found in 19/70 squamous cell carcinomas, 6/18 malignant and 1/21 benign salivary neoplasms. CA 19-9 displayed higher values (greater than 37 units/ml) in 9/68 squamous cell carcinomas, 4/18 malignant and none of 21 benign salivary gland tumours. Combination of CEA and CA-50 analyses increased the proportion of elevated values to 30/70 in squamous cell carcinomas and 10/18 in salivary gland malignancies. In squamous cell carcinomas no correlation between staging or grading and serum levels was detected for any of the markers. Among malignant salivary gland tumours, CA-50 displayed enhanced serum values in 4/6 mucoepidermoid carcinomas. The mean values for CA-50 and CA 19-9 serum levels were significantly higher for malignant salivary gland neoplasms compared to benign tumours. There was a close correlation between CA-50 and CA 19-9 serum levels. Although, the results suggest that at present none of the tumour markers tested have a place alone in the routine examination of patients with tumours affecting the head and neck region, further studies on salivary gland neoplasms and combinations of the tumour markers are justified.

Antigens, Neoplasm↗

Iontophoretic study of skin vessel reactivity in atopic dermatitis and its correlation to serum IgE levels.

Skin vessel reactivity was studied by means of an iontophoretic technique in 19 adult patients with atopic dermatitis. Fifteen patients were available for reinvestigation some 6 months later in winter. Compared with a control group, we found a significantly increased sensitivity in summer of dermal skin vessels toward the alpha 1-agonist phenylephrine. Patients with elevated serum IgE levels seemed to be more sensitive to phenylephrine. However, the difference was not significant. Isoproterenol, the beta-adrenoceptor agonist, induced blanching (as opposed to erythema) in 7 of 19 (37%) atopic dermatitis patients in summer and in 9 of 15 (60%) in winter compared with 1 of 36 in the control groups. This blanching was antagonized by the alpha-blocker phentolamine. From the results we concluded that there may be an increased alpha-adrenoceptor reactivity and/or a decreased beta-adrenoceptor reactivity in atopic dermatitis patients, which might be a primary defect.

Adult↗

Estramustine binding protein and anti-proliferative effect of estramustine in human glioma cell lines.

Four human cell lines derived from malignant gliomas were immunohistochemically examined for their content of estramustine-binding protein (EMBP). EMBP was detected in a large amount in all glioma cells during the entire cell cycle. EMBP has previously been demonstrated to be the major receptor protein in prostatic cancers for the cytostatic drug estramustine-phosphate (EMP). EMP caused a dose-dependent inhibition of exponentially growing cells by increasing the number of cells in G2/M stage of the cell cycle as monitored by flow cytofluorometry. The effect may be coupled to arrest of the glioma cells at metaphase. The presence of EMBP may suggest a selective binding and effect of EMP in glioma cells.

Carrier Proteins↗

Increased peripheral alpha-adrenoceptor response in allergic asthmatics.

The peripheral alpha-adrenoceptor reactivity, measured as dermal blanching response to iontophoretically administered phenylephrine, was studied in 28 allergic asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy controls. The blanching response, which has previously been demonstrated to be mediated via alpha 1-adrenoceptors, was found to be significantly increased in allergic asthmatics compared with controls. It is suggested that there is an increased peripheral alpha-adrenoceptor reactivity in allergic asthma.

Adolescent↗

Dopamine actions in vitro on enzyme and electrolyte secretion from normal and sympathectomized rat parotid glands.

1. Adult rats were denervated unilaterally by removal of the left superior cervical ganglion or chemically denervated with 6-hydroxydopamine or reserpine. Two weeks later the parotid glands were used for in vitro secretory studies and their catecholamines and major metabolites were measured. 2. Noradrenaline concentrations were reduced 2 weeks after surgical sympathectomy and reserpine pre-treatment 18 h previously, whereas 6-hydroxydopamine pre-treatment for 3 days reduced both noradrenaline and dopamine concentrations. 3. Dopamine caused a prominent amylase release from incubated control glands. However, a subsensitivity for dopamine-induced amylase release was recorded on the denervated side. 4. Dopamine caused a prominent potassium efflux measured as 86Rb+ efflux from control glands, but was without effect in denervated glands. This is in contrast to noradrenaline-induced 86Rb+ efflux which was equally effective in both denervated and control glands. 5. Dopamine caused [3H]noradrenaline efflux in control glands, but was without effect in surgically denervated glands and in glands pre-treated with reserpine or 6-hydroxydopamine. 6. It is concluded that dopamine-induced potassium release is caused by a presynaptic action on noradrenergic nerves, whereas dopamine-induced amylase release has a presynaptic and a postsynaptic component. The results suggest a specific action of dopamine in salivary glands, with different effects on enzyme release and ionic fluxes.

Amylases↗

Mucin in gall bladder bile of gall stone patients: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.

The concentration of hexosamine, a marker for mucin, was determined and related to the degree of cholesterol saturation and to the occurrence of cholesterol crystals in gall bladder bile of gall stone patients (n = 40) and gall stone free subjects (n = 25). Ten of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and eight with ursodeoxycholic acid (UDCA) three to four weeks before cholecystectomy. The hexosamine content was significantly higher in gall stone patients (137 (19) ng/ml, mean (SE) than in gall stone free subjects (83 (9) ng/ml, p less than 0.02). Treatment with CDCA or UDCA decreased cholesterol saturation, but did not significantly affect the hexosamine concentration. There was no difference in hexosamine concentration between gall stone patients with and without cholesterol crystals. The results do not support the hypothesis that the degree of cholesterol saturation is important for the mucin content of gall bladder bile in man. Neither do the data indicate that the formation and occurrence of cholesterol crystals in gall bladder bile from gall stone patients is caused by an increased concentration of mucin. As the studies were conducted on patients who had already had gall stones for several years, however, an effect of mucin in the very early stage of gall stone formation cannot be completely excluded.

Adult↗

Doxorubicin and epirubicin iron-induced generation of free radicals in vitro. A comparative study.

To ascertain any differences in myocardial injury exerted by the anthracyclines doxorubicin and epirubicin, their ability to generate oxygen free radicals when mixed with Fe(II) was examined in vitro using an oxygen electrode. 5-250 micrograms/ml doxorubicin or epirubicin consumed oxygen when mixed with 50 or 100 mumol/l Fe(II). Addition of 75 mumol/l cytochrome C showed that of the consumed oxygen, approximately 80% entered the monovalent pathway of oxygen reduction. The strong inhibitory effect of 250 mg/l catalase indicates that most of the superoxide radicals generated are further reduced to hydrogen peroxide by both anthracyclines. Addition of metal chelators DTPA (100 mumol/l), or DDTC (50 mumol/l) did not affect oxygen consumption, whereas EDTA (100 mumol/l) or desferrioxamine (100 mumol/l) with anthracyclines and Fe(II) rather stimulated oxygen consumption. It is concluded that there are no significant differences in the amount or proportion of generated oxygen free radicals between doxorubicin and epirubicin when mixed with Fe(II) in a cell-free system in vitro. Thus, the ability of the anthracyclines, in conjunction with iron alone, to generate radicals does not explain the differences of the drugs in causing myocardial injury.

Doxorubicin↗

Salivary glands in long-term alloxan-diabetic rats. A quantitative light and electron-microscopic study.

Fifty untreated diabetic animals were compared with 58 age-matched non-diabetic controls. Reduced salivary gland weight was evident after one month's diabetes and this was unchanged after 12 months of diabetes. Submandibular/sublingual gland weight was proportional to the reduced body weight in the diabetic rats. Parotid gland weight, however, was proportionally more reduced. Only diabetic rats had lipid inclusions in the acinar cells of their submandibular glands and the morphometrically estimated amount of inclusions was positively correlated to the blood glucose level. Acinar cell size was significantly increased in long-term diabetic rats as compared with short-term diabetic rats and controls. Capillary basement membrane width was significantly increased in long-term diabetic rats compared with age-matched controls and with short-term diabetic rats. Thus, both the degree and duration of diabetes have a major effect on salivary gland morphology in alloxan diabetic rats.

Animals↗