| 1. |
- Karlsson, Britt M., et al.
(författare)
-
Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition
- 2003
-
Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 108:2, s. 141-149
-
Tidskriftsartikel (refereegranskat)abstract
- The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.
|
|
| 2. |
- Karlsson, Britt M., et al.
(författare)
-
The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.
- 1997
-
Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 49:3, s. 296-300
-
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.
|
|
| 3. |
- Koch, Bo L., et al.
(författare)
-
Inhalation of substance P and thiorphan : acute toxicity and effects on respiration in conscious guinea pigs.
- 1999
-
Ingår i: Journal of Applied Toxicology. - 0260-437X .- 1099-1263. ; 19:1, s. 19-23
-
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.
|
|
| 4. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
-
Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation
- 2000
-
Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 105:3, s. 215-226
-
Tidskriftsartikel (refereegranskat)abstract
- The acute effects of cigarette smoking and hypoxia on the cerebral and testicular microcirculation were studied in anestethised adult rats. Smoking for 2 min did not influence arterial pO2, pCO2 or pH but it induced an increase in cerebral blood flow by 34% and inhibited vasomotion in the testis for about 1 h. One hour after smoke exposure apnea induced a slight increase in arterial pCO2, a significant decrease in pO2, and an increase in cerebral blood flow (CBF) by 54%. In animals not previously exposed to cigarette smoke apnea increased CBF by 121%, demonstrating that a short-term exposure to tobacco smoke influences the cerebrovascular reactivity for more than one hour. In the testis, apnea resulted in a decreased blood flow by 39% and a complete depression of vasomotion. Breathing 10% O2/90% N2 resulted in moderate hypoxia, a total disappearance of the vasomotion in the testis, a 24% decrease in testicular blood flow, but a 23% increase in CBF.Our results indicate that short-term exposure to tobacco smoke induces marked acute vascular effects in both the brain and the testis. Apnea and moderate hypoxia elicited totyally different effects in the brain and testis, inicating different vascular control mechanisms.
|
|
| 5. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
-
Nitric oxide inhibition by L-NAME but not 7-NI induces a transient increase in cortical cerebral blood flow and affects the cerebrovasodilation induced by TRH
- 2003
-
Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 24:4, s. 579-583
-
Tidskriftsartikel (refereegranskat)abstract
- The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiological effects. One of these is the cerebrovasodilating effect, which has been described under several different conditions. The final mechanism for this effect is unknown. In the present study, we found an initial atropine-resistant cerebral vasodilation (24%) elicited by the NOS inhibitor L-NAME in the rat. D-NAME and 7-NI did not produce this effect. TRH (300 microg kg(-1), i.v.) induced an increase in cerebral blood flow by 62%. L-NAME reduced this effect significantly. The cerebrovasodilating mechanism of TRH, at least in part, is endothelial NO dependent as the neuronal 7-NI NOS inhibitor does not affect the TRH response.
|
|
| 6. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
-
The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.
- 1998
-
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 19:10, s. 1675-1677
-
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.
|
|
| 7. |
- Larsson, Jan, et al.
(författare)
-
Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.
- 1996
-
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 17:2, s. 293-297
-
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.
|
|
| 8. |
- Magnusson, B. M., et al.
(författare)
-
Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH
- 2001
-
Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 22:1, s. 73-79
-
Tidskriftsartikel (refereegranskat)abstract
- Besides its well known endocrinological effects, thyrotropin-releasing hormone (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the presence of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terpene on the transdermal penetration of the peptides across full-thickness rat skin were studied. Steady-state permeability values for TRH and M-TRH were 8.7 +/- 2.2 and 6.7 +/- 1.4 microg/cm(2) h, respectively. The addition of 3 % terpene in combination with 47 % ethanol increased the penetration of TRH and M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 microg/cm(2) h, respectively. Rats were studied in vivo for release of thyroid-stimulating hormone (TSH) as a biologic effect after transdermally delivered peptide. Topical application of TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/- 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respectively. It is concluded that, in the rat, peptides can be absorbed through the skin with retained biologic activity, and in amounts sufficient to elicit a physiological response.
|
|
| 9. |
- Magnusson, Beatrice M., et al.
(författare)
-
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
-
Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 76:2, s. 129-132
-
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.
|
|
| 10. |
- Magnusson, B.M., et al.
(författare)
-
In vitro percutaneous penetration of topically applied capsaicin in relation to in vivo sensation responses
- 2000
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 195:1-2, s. 55-62
-
Tidskriftsartikel (refereegranskat)abstract
- Capsaicin, the primary pungent element in several spices, elicits a variety of physiological effects which are due to neurogenic responses. The aim of the study was to explore the in vivo sensation responses of capsaicin and to compare the results with the in vitro percutaneous absorption of the substance. The overall objectives were to determining an in vitro-in vivo correlation for capsaicin. Capsaicin was applied in a chamber on the volar forearm of twelve volunteers and in a flow-through diffusion chamber on excised human epidermal membranes. Topical administration of capsaicin produced a complex cutaneous sensation that changed in intensity and quality as a function of time and was characterized by sting, prick, burn and pain. Percutaneous steady-state penetrations of capsaicin with a receptor fluid consisting either of 4% bovine serum albumin in phosphate buffered saline or 50% ethanol in water were 28.2+/-2.7 and 29.6+/-2.9 microg/cm(2) per h, respectively. The corresponding cumulative penetrated amounts of capsaicin after 30 min were 14. 7+/-1.7 and 19.2+/-2.1 microg/cm(2), respectively. The present investigation indicates that there is a good correlation between in vivo physiological responses and in vitro percutaneous penetration of topically applied capsaicin.
|
|
