| 1. |
- Malm, Jan, Professor, 1957-, et al.
(författare)
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Cerebrospinal fluid shunt dynamics in patients with idiopathic adult hydrocephalus syndrome.
- 1995
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 58:6, s. 715-723
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to assess CSF dynamics of different shunt constructions in patients with adult hydrocephalus syndrome and correlate these findings to clinical outcome, neuroradiology, and the specifications of the shunts provided by the manufacturer. Thirty four patients with idiopathic adult hydrocephalus (normal pressure hydrocephalus) syndrome were included in a prospective, consecutive case series. A differential pressure valve (Cordis Hakim standard system) was used in 28 patients and a variable resistance valve (Cordis Orbis-Sigma) in six. A constant pressure infusion method was used; CSF pressure and conductance were determined before surgery. Three months after shunt placement CSF pressure, the "pressure v flow" curve, and gravity induced flow were measured. There was no difference between mean preoperative and postoperative resting CSF pressures in patients with Hakim shunts. The opening pressures of the Hakim shunts were higher than the value proposed by the manufacturer. A pronounced gravity effect induced CSF flow and decrease of the CSF pressure. In functioning variable resistance valves, CSF dynamics normalised postoperatively. There was no gravity effect and the characteristics shaped "pressure v flow" curve was sometimes seen. Six patients (three differential pressure valves, three variable resistance valves) had non-functioning shunts. Four of these patients were improved after the operation but improvement was transient in three. In all patients, there was no relation between the width of the ventricles and clinical improvement or CSF pressure. In conclusion, the differential pressure valve system does not behave according to the specifications provided by the manufacturer. A decrease in CSF pressure in patients with this shunt was solely due to the effect of gravity. Eleven percent of the differential pressure valves and 50% of the variable resistance valves were non-functioning. In the functioning variable resistance valves, the antisiphon system seems to be effective.
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| 2. |
- Johansson, Mikael, et al.
(författare)
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Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model
- 1997
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Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 41:1, s. 237-244
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.
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| 3. |
- Karlsson, Britt M., et al.
(författare)
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The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.
- 1997
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 49:3, s. 296-300
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Tidskriftsartikel (refereegranskat)abstract
- The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.
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| 4. |
- Koch, Bo L., et al.
(författare)
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Inhalation of substance P and thiorphan : acute toxicity and effects on respiration in conscious guinea pigs.
- 1999
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Ingår i: Journal of Applied Toxicology. - 0260-437X .- 1099-1263. ; 19:1, s. 19-23
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Tidskriftsartikel (refereegranskat)abstract
- Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.
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| 5. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.
- 1998
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 19:10, s. 1675-1677
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.
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| 6. |
- Larsson, Jan, et al.
(författare)
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Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.
- 1996
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 17:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- The effects of IV TRH pretreatment on induction of anesthesia with propofol or pentobarbital were investigated in rats. The effects of IV TRH, administered after induction, on duration of propofol anesthesia and the interaction with atropine were also studied. The doses of propofol or pentobarbital were not influenced by TRH. TRH reduced duration of anesthesia after propofol, with higher brain concentrations of propofol at recovery. Atropine did not block this effect, but given alone prolonged duration of anesthesia. It is concluded that TRH shortens the duration of propofol anesthesia, probably due to a pharmacodynamic effect and not to a pharmacokinetic interaction.
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| 7. |
- Magnusson, Beatrice M., et al.
(författare)
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Effects of topical application of capsaicin to human skin : a comparison of effects evaluated by visual assessment, sensation registration, skin blood flow and cutaneous impedance measurements.
- 1996
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Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 76:2, s. 129-132
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Tidskriftsartikel (refereegranskat)abstract
- A new non-invasive device, which enables local measurements of electrical impedance, has been used to evaluate the degree of irritation in human skin. The results have been compared with visual scoring, sensations and laser Doppler flowmetry. Capsaicin (50 microliters 1% solution) and control solutions (50 microliters 50% ethanol) were applied in a chamber for 30 min on the volar forearm of 7 volunteers. Values were recorded before application and during the total test period of 4.5 h. Sensations like sting/prick, burn and pain were produced by this treatment, and the flare response was observed. Using the non-invasive laser Doppler flow technique to measure blood flow in human skin, we have shown that topical application of capsaicin abolishes the vasodilator response to local heat provocation (40 degrees C). There was close agreement among values obtained using visual assessments, sensations and laser Doppler flowmetry. Results obtained using electrical impedance measurements were not consistent with the other three methods.
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| 8. |
- Magnusson, Beatrice M., et al.
(författare)
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Terpene-enhanced transdermal permeation of water and ethanol in human epidermis
- 1997
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 77:4, s. 264-267
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Tidskriftsartikel (refereegranskat)abstract
- The study was performed to investigate the effect of penetration enhancers on the stratum corneum barrier. Epidermal membranes were prepared from freeze-stored (-70 degrees C) Caucasian breast skin and mounted in a flow-through diffusion cell. The validity of the freeze storage procedure was verified by measurement of [3H]-water penetration. The effect of the cyclic terpene, carveol, on the transdermal penetration of water and ethanol was studied in vitro. Control ethanol and water penetration measured with a donor solution of 50% ethanol/PBS (w/w) was 1.9+/-0.2 and 3.6+/-0.5 x 10(-3) cm/h. The addition of 3% carveol to the donor solution increased the permeation of ethanol and water after 4 h to 8.3+/-1.1 and 12.5+/-1.9 x 10(-3) cm/h, respectively. In a separate experiment, terpinen-4-ol and alpha-terpineol were also tested, in addition to carveol, for effect on tritium flux. No significant difference in maximum tritium flux was obtained between the three terpenes studied. The maximum increase in permeability coefficients of carveol, terpinen-4-ol and alpha-terpineol was 10.6, 8.7 and 10.9, respectively.
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