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Biomedical subjects

V Saano

Publications and source records attributed to V Saano.

At least 19 recordsLinked to original sources
PubMed2000

Water-activated, pH-controlled patch in transdermal administration of timolol. II. Drug absorption and skin irritation.

The feasibility of the water-activated, pH-controlled silicone reservoir devices for transdermal administration was investigated using timolol maleate as a model drug. Timolol patches were applied to the arm of 12 volunteers for 81 h, two patches per subject. Timolol absorption from patches was compared to that from a peroral timolol tablet formulation (Blocanol((R)) 10 mg). Furthermore, in vivo plasma levels of timolol were compared with those predicted by kinetic simulations. Skin irritation induced by timolol patches was assessed by visual scoring and color reflectance measurements. With water-activated, pH-controlled patches both steady-state concentrations of timolol in plasma and its duration could be controlled. However, a considerable, inter-individual variability in the transdermal absorption of timolol was observed. This is due to the high fractional skin control in timolol delivery. Timolol patches were well tolerated by subjects. Skin irritation induced by the combination of timolol with long-term occlusion was mild, and after removal of the patches, skin changes were practically reversed in 24 h. Simulation model was useful in prediction of timolol levels in plasma after transdermal administration.

Administration, Cutaneous↗
PubMed1999

Effects of repeated low dose administration and withdrawal of haloperidol on sexual behaviour of male rats.

Neuroleptics are known to cause anhedonia and attenuate sexual behaviour at therapeutic doses in humans. These effects are assumed to result from the dopamine antagonism of the drugs. It has been observed that a mixed dopamine D1/D2 antagonist, haloperidol, may cause a reduction in the number of intromissions required to achieve ejaculation. On the other hand, dopamine antagonists are considered unable to modify sexual behaviour once the copulatory sequence is initiated. In this study, male rats received low doses of haloperidol (30 or 60 microg/kg) before the investigation of sexual behaviour in five consecutive days and the mating test was repeated after withdrawal periods of four and five days. Haloperidol dose-dependently reduced intromission frequency, and this effect was maintained for four days after withdrawal. Ejaculation latency was reduced in all groups, including controls. The results indicate that at low doses haloperidol dose-dependently reduces intromission frequency, and the effect of a repeated dosage may persist several days after cessation of medication.

Animals↗
PubMed1998

Correlation between ciliary beat frequency and the structure of ciliated epithelia in pathologic human nasal mucosa.

The structure and function of ciliated epithelium were studied in 44 human nasal mucosa samples using a photoelectric method and scanning electron microscopy (SEM). The ciliary beat frequency (CBF) of cases with recurrent or chronic sinusitis was 9.1 +/- 5.4 Hz. In eight of the samples (18.2%) no ciliary activity was detected. The amount of ciliated cells, the orientation of cilia, epithelial metaplasia, and secretion were found to be explanatory factors accounting for the decreased ciliary activity. Ciliary disorientation and a lack of ciliated cells in SEM correlated with low ciliary activity. In cases where sinusitis secretion was not seen, the CBF was slower than in cases with mucus or mucopurulent secretion. Sinusitis with disoriented cilia, a loss of ciliated cells, and a lack of mucosal secretion is associated with a decreased CBF. This may lead to impaired mucociliary clearance and increase the risk of recurrent and chronic sinusitis.

Adolescent↗
PubMed1997

Influence of ageing on ciliary beat frequency and on ciliary response to leukotriene D4 in guinea-pig tracheal epithelium.

1. In the present study on guinea-pig tracheal epithelium, the influence of age on ciliary beat frequency (CBF) was investigated. 2. An age-dependent decrease in CBF was seen: as the age of the guinea-pig increased from 0.9 to 16.3 months, CBF decreased from 20.2 to 6.9 Hz. 3. The effect of leukotriene D4 (LTD4) on CBF was also examined using tracheal explants from guinea-pigs of varying ages. The lower CBF of the older animal was increased by LTD4 to a larger extent than was the higher CBF seen in explants taken from younger animals. 4. Ciliary activity and possibly also the sensitivity of the cilia to drugs, seems to be dependent upon the age of the animal, which has to be taken into consideration when comparing the results of different studies on the effects of xenobiotics on mucociliary function.

Aging↗
PubMed1997

Experimental studies on the antitussive properties of the new xanthine derivative 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]. 1st communication: in vivo demonstration of the effects on animal models of cough and of mucociliary clearance.

CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) is a new xanthine derivative synthesized with the purpose to develop a highly safe compound against several pulmonary disorders, especially for the treatment of acute and chronic cough. CH-13584 showed acute and chronic antitussive activity on citric acid spray-evoked cough model in guinea-pig. CH-13584 was also effective on capsaicine spray and mechanical irritation-induced cough in guinea-pig and rabbit, respectively. The effectivity of CH-13584 on antitussive tests reached and in some cases even exceeded the effectivity of the reference compounds. The compound increased the mucociliary clearance at lower doses than bromhexine.

Animals↗
PubMed1996

Effect of leukotriene D4 on ciliary activity in human, guinea-pig and rat respiratory mucosa.

Leukotriene D4 (LTD4) is a potent bronchoconstrictor and inflammatory mediator in asthma. Data concerning the effects of LTD4 on ciliary function in the respiratory tract are sparse and contradictory. The purpose of the present study was to clarify the effects of LTD4 on mucociliary activity using the tracheal mucosa of two laboratory animal species, guinea-pig and rat, as well as human nasal mucosa. The ciliary beat frequency (CBF) was measured photoelectrically and determined by Fast Fourier Transform computer analysis. Additionally the structure of ciliated epithelia of guinea-pig trachea after LTD4-immersion was investigated using a scanning electron microscope (SEM). In all tissues, LTD4 increased CBF showing a bell-shaped dose-response curve. The maximum effect was 75 +/- 30% in guinea-pig at 10(-9) mol/l, 119 +/- 49% in rat at 10(-7) mol/l, and 86 +/- 28% at 10(-6) mol/l in human tissue. In guinea-pig tracheal mucosa, there was an indication of an increase in the amount of mucus and disorientation of cilia were seen by SEM after immersion in LTD4. These findings suggest that LTD4 stimulates ciliary activity, but impairs the orientation of cilia.

Adolescent↗
PubMed1995

Triethyllead decreases central benzodiazepine receptor binding in rat cerebellum ex vivo.

Effect of triethyllead on the specific [3H]flunitrazepam binding was studied in rat cortical and cerebellar P2 fractions in vitro and in tissue homogenates of several rat brain regions ex vivo after 5 daily subcutaneous doses of 1.9 mg/kg triethyllead acetate to rats. Up to concentration of 100 microM, triethyllead did not affect significantly the specific [3H]flunitrazepam binding but attenuated marginally (14-18%) the GABAA receptor agonist, muscimol-induced elevation of [3H]flunitrazepam binding in cerebellar tissue. After the subacute treatment of rats with triethyllead, the specific [3H]flunitrazepam binding was 27% lower in cerebellum compared to control animals. In other brain regions the receptor binding was not changed. The data suggest that triethyllead modified the cerebellar GABAA receptor complex causing decreased binding in the benzodiazepine site. Such an inhibitory effect in the GABAA receptor complex may decrease cerebellar inhibitory output and augment the triethyllead induced convulsions and tremor.

Animals↗
PubMed1995

Methylmercury modulates GABAA receptor complex differentially in rat cortical and cerebellar membranes in vitro.

Effects of methylmercury (MetHg) on the specific [3H]flunitrazepam binding were studied in rat cortical and cerebellar P2-fractions in vitro. MetHg did not affect significantly the specific [3H]flunitrazepam binding in unwashed P2-fraction but increased it marginally (by 16%) at 100 microM in washed P2-fraction, in both brain regions. Muscimol (3 microM), a GABAA agonist, stimulated the [3H]flunitrazepam binding by 30% to 50% depending on the brain region. In washed cerebellar membranes the enhancing response of muscimol was 10 to 14% lower after preincubation of the tissue with MetHg but in cerebral cortex MetHg did not modulate the muscimol response at all. The results indicate that Met-Hg may have region specific effects on GABAA receptors in vitro and the effect may depend on the occupational state of the GABA binding domain of the receptor complex.

Animals↗
PubMed1995

Effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive.

The effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive containing 30 micrograms ethinyl estradiol and 75 micrograms gestodene were assessed in a randomized, double-blind, placebo-controlled parallel-group study in healthy premenopausal female volunteers established in a regimen of oral contraceptive use. They received either placebo or 2400 mg/day felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive cycles (months 1 and 2). Pharmacokinetic assessments of ethinyl estradiol and gestodene were performed on day 14 of both cycles. To determine whether ovulation occurred, plasma progesterone and urinary luteinizing hormone levels were measured, and diaries recording vaginal bleeding were kept. Felbamate treatment resulted in a significant 42% decrease in gestodene area under the plasma concentration-time curve (0 to 24 hours) (p = 0.018) compared with baseline, whereas a minor but not clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol. There were no changes in the pharmacokinetics of ethinyl estradiol or gestodene after placebo treatment. No volunteer showed hormonal evidence of ovulation; however, one volunteer reported the onset of intermenstrual bleeding during felbamate treatment. Because of the effect of felbamate on the pharmacokinetics of gestodene and the report of intermenstrual bleeding, it is possible that the contraceptive efficacy of low-dose combination oral contraceptives may be adversely affected during felbamate treatment.

Adult↗
PubMed1995

Ciliary ultrastructure and beating activity in rat and guinea-pig respiratory mucosa.

1. The rat and the guinea-pig are commonly used animals when the effects of drugs on ciliary activity in respiratory airways are studied. There are few data concerning the possible differences in ciliary function between these two animals. 2. Using a photodetector method we measured the ciliary beating frequency (CBF) from the upper part of the trachea, the lower part of the trachea and the distal part of the main bronchi (subsegmental bronchi) of rat and guinea-pig respiratory tract. In addition, the structure of the cilia was studied using scanning electron microscopy (SEM). 3. CBF in the rat respiratory tract was significantly lower than in the guinea-pigs. In the upper trachea, the CBF for rat was 12.7 beats/s and 15.3 beats/s for guinea-pig. The respective values were 9.2/16.0 beats/s in the lower part of the trachea and 6.9/13.8 beats/s in subsegmental bronchi. In both rats and guinea-pigs CBF was lower in the subsegmental bronchi than in the trachea (rat: 25.0-45.7%, guinea-pig: 9.8-13.8%). 4. In addition to higher CBF, the quality of the photo-electrical signal was better from guinea-pig tissues, probably as a result of the larger amounts of ciliated cells and longer cilia of guinea-pig respiratory epithelial compared to those in rat mucosa. 5. SEM showed that the rat cilia were on average shorter (3.6 vs 4.3 microns) and thinner (0.19 vs 0.22 microns) than those of the guinea-pig. Rat mucosa was markedly less ciliated than the respiratory mucosa of the guinea-pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Controlled ocular timolol delivery: systemic absorption and intraocular pressure effects in humans.

Timolol eyedrops may cause systemic side-effects in glaucoma patients due to absorption of the drug into systemic circulation. In a previous study, timolol concentrations in plasma were reduced if timolol was administered in ocular inserts instead of eyedrops. We compared the intraocular pressure lowering effect and systemic absorption of timolol inserts to those of 0.5% timolol eyedrops in humans. Inserts of silicone tubing released 90.3 +/- 13.9 micrograms of timolol in 24 hours in vivo. Timolol inserts afforded similar decreases in intraocular pressure in open-angle glaucoma patients as did b.i.d. eyedrops, but produced lower peak timolol concentrations in plasma, 0.70 +/- 0.10 ng/ml and 0.24 +/- 0.05 ng/ml, respectively. After eyedrops, peak concentrations were achieved at 15.0 +/- 2.2 min, while application of an insert resulted in a delayed peak (tmax = 623 +/- 195 min). The insert resulted in a higher systemically absorbed fraction of the timolol dose than the eyedrop, but the peak timolol concentration and daily absorbed amount of timolol were decreased. The release rate of timolol from the inserts in vivo was only slightly less than that in vitro. Silicone devices are useful for clinical testing of controlled delivery properties of ocular drugs.

Absorption↗
PubMed1994

Ciliary beat frequency at six levels of the respiratory tract in cow, dog, guinea-pig, pig, rabbit and rat.

1. The ciliary beat frequency (CBF) of six animal species from six regions of the respiratory tract were measured: inferior turbinate, nasopharynx, the upper part of trachea from first to second cartilage, the lower part of trachea, main bronchus and subsegmental bronchi. Cow, pig, dog, rabbit, guinea-pig and rat were studied. 2. There were no significant differences in the CBF values between cow, pig and dog, and the ciliary activity was essentially the same (11.3-16.9 Hz) in all parts of the respiratory tract. 3. In the rat, the CBF was slower, especially in subsegmental bronchi (6.8 Hz). 4. In general, CBF was higher in upper than lower airways, with the exception of guinea-pig. 5. Signal quality was the highest in guinea-pig tissue, whereas rat tissue produced the signal with the widest variation in CBF and the highest proportion of distorted waveforms. 6. Therefore, for studying drug effects on ciliary activity, guinea-pig seems to be a more suitable animal than the more commonly used rabbit or rat. In drug comparisons, the same part of the respiratory tract and the same animal species should be used.

Analysis of Variance↗