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Biomedical subjects

B Sadowski

Publications and source records attributed to B Sadowski.

At least 19 recordsLinked to original sources
PubMed1995

Oligogenic determination of morphine analgesic magnitude: a genetic analysis of selectively bred mouse lines.

Two ongoing selective breeding projects have produced mice that display divergent analgesic responses to morphine. These two projects have selected for similar phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland). Evidence suggests genetic commonalities between mice of the two projects. Using a Mendelian breeding protocol, we have recently found that one or two genetic loci predominantly determine the high morphine analgesia exhibited by HA mice. In the present study we demonstrate that the differential morphine analgesia (5 mg/kg, i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly determined by two unlinked loci. A complementation analysis, in which the analgesic responses to morphine of the recessive homozygotes of each project (HAR and HA) were compared to those of their hybrid offspring (HAR x HA), revealed that different genetic loci have been fixed in each project. An intriguing bimodal distribution was observed in the HAR x HA population: Some HAR x HA hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice were comparable to those of their low-line parents. These findings indicate not only that different loci were responsible for producing high morphine responders in each selection project but that these distinct loci can interact synergistically to produce "superhigh" and "superlow" responders.

Analgesics, Opioid↗
PubMed1995

[Biological corneal replacement--an alternative to keratoplasty and keratoprosthesis? A pilot study with heterologous hyaline cartilage in the rabbit model].

BACKGROUND: In patients with corneal opacity caused by diseases like okular pemphigoid, Stevens-Johnson-Syndrome or burns, visual rehabilitation can only be achieved with keratoplasty or keratoprosthesis. The first has generally a poor prognosis in these circumstances, and the latter bears several problems in the postoperative course as well. A biological, corneal replacement could possibly combine the advantages offered by keratoplasty (no interaction between host tissue and plastic) and keratoprosthesis (more permanent transparency). Theoretical considerations and practical experience suggest that the best candidate would be hyaline cartilage. MATERIAL AND METHODS: Bovine sterni were used to obtain circular cartilage slices which were approximately 60 microns thick, having a diameter of approximately 6 mm. These slices were implanted in one eye each of 4 rabbits instead of the natural cornea. The eyes were enucleated after 8 to 29 days. RESULTS: The cartilage remained so transparent that the iris and to a certain extent the fundus blood vessels could be visualized. Connective tissue served to bind the host cornea to the cartilage, but did not infiltrate the cartilage. Perforation was observed in 3 animals. The extent of epithelialization of the cartilage slices ranged form ca. 30% to 95%. None of the animals exhibited an intraocular inflammation. The cartilage did not proliferate and remained avascular. Secondary intraocular changes, with the exception of anterior synechiae, could not be detected. CONCLUSIONS: A tissue for biological corneal replacement has to fulfill many requirements which to a certain extent can be achieved with the use of hyaline cartilage. Despite numerous, unsolved problems, a biological corneal replacement as an alternative to keratoplasty and keratoprosthesis in cases of corneal blindness does not seem out of imagination.

Animals↗
PubMed1995

Selective cone dystrophy with protan genotype.

PURPOSE: To determine the functional defects in two male patients with progressive cone dystrophy and hybrid L-M cone pigment genes. METHODS: Clinical evaluation, standard electroretinography, and electrooculography were performed in two affected patients and two family members. Measurements of spectral sensitivity and transient tritanopia were made in both patients. RESULTS: In the patients, visual acuity varied between 20/50 and 20/100. The electroretinogram showed reduced flicker responses. When light adapted, a-wave amplitudes were borderline, but b-wave amplitudes were reduced severely. Electroretinography with chromatic stimuli showed a difference between well-preserved responses to green and markedly reduced responses to red stimuli. Spectral sensitivity measurement revealed a lack of L (long-wavelength sensitive; red) cone function and normal function of the S (short-wavelength sensitive; blue) and M (middle-wavelength sensitive; green) cones. Transient tritanopia was abnormal, indicating a severe disturbance of cone-cone interaction. CONCLUSIONS: Progressive cone dystrophy with predominant dysfunction of L cones exists in both patients. The cone dystrophy may be caused by a rearrangement of the X-chromosome pigment gene array that is associated with the deletion of L-cone sequences and the formation of hybrid L-M cone pigment genes. It cannot be excluded, however, that both patients have protanopia and that cone dystrophy developed because of other causes.

Adult↗
PubMed1995

[Visual acuity, refraction and color vision after implantation of foldable silicon lenses].

Implantation of intraocular lenses through a small opening is possible with phacoemulsification and foldable silicon lenses. There is little traumatic effect, which is positive for the healing process and the postoperative results of visual acuity and refraction. Because of alteration of the optic media, deteriorated sensation is possible. We investigated 28 patients with foldable silicon lenses after phacoemulsification. Pre- and postoperatively (1 day, 1 week, 3, 6, 12, 18 and 24 months) visual acuity and astigmatism were measured. As the testing of color vision is a sensitive method for the detection of disturbance in sensation because of altered optic media this was performed 24 months postoperatively using the pseudoisochromatic plates of Ishihara and Ichikawa and the color arrangement tests, Farnsworth Panel D-15 desaturated and the Farnsworth Munsell 100 hue test. The results of this study confirm quicker rehabilitation of visual function and a lower rate of operatively induced astigmatism. A slight blue color vision deficiency results as consequence to altered optic media, but there is no effect on daily life.

Aged↗
PubMed1994

Morphine analgesia and tolerance in mice selectively bred for divergent swim stress-induced analgesia.

Morphine-induced analgesia and tolerance were examined in Swiss Webster mice selectively bred for high and low swim stress-induced analgesia. Morphine produced a dose-dependent analgesia in both lines; it was 4-fold more potent in the high analgesia line than in the low analgesia line. Despite the differences in morphine-induced analgesia, the degree of tolerance was the same in both lines. Together, these data suggest that selective breeding of mice for high and low swim stress-induced analgesia produced a striking difference in morphine-induced analgesia without affecting the degree of tolerance. Thus, while there is a common genetic determination in swim stress-induced and morphine-induced analgesia, the development of tolerance to morphine possibly relies on a different genetic background.

Analgesia↗
PubMed1994

Mu-opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia.

Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [3H]naloxone. HA mice were found to have significantly higher whole-brain receptor density (Bmax) than LA mice in whole brain homogenates; no significant difference in affinity (Kd) was observed. Quantitative autoradiography confirmed the line difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [3H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant line differences were observed in any other brain locus. Thalamic mu receptors may therefore play an important role in a central 'volume control' mechanism of pain inhibition, and underlie individual differences in the responses of mice to opiate analgesic drugs.

Analgesia↗
PubMed1994

[Corneal manifestations in Vitamin A deficiency].

BACKGROUND: Vitamin A, the fat soluble vitamin, must be supplied orally before resorption in the mucosa of the small intestine and storage in the liver. Vitamin A deficiency can cause alterations in the anterior segment of the eye, from Bitot spots, which are reversible, to irreversible keratomalacia. PATIENTS AND METHODS: 5 patients suffering from manifestations at the cornea underwent ophthalmological, general and dermatological investigation and measurements of the vitamin A, retinol-binding protein and, in one patient, zinc were performed. 4 patients suffered from cornea manifestations, reaching from almost a reactive ulceration to spontaneous perforation. One patient had relapsing episcleritis. All patients were alcoholics, had hepatopathies and dermatological diseases. Vitamin A and retinol-binding protein were decreased and in one patient a highly decreased zinc was measured. In one patient a systemical and local substitution of vitamin A increased the clinical findings significantly. Two eyes had to undergo a keratoplasty à chaud, one evisceration had to be done. CONCLUSION: Vitamin A deficiency can be the reason for bilateral painless cornea manifestations. An interdisciplinary cooperation is essential for the elaboration of the diagnosis and the treatment.

Adult↗
PubMed1994

[Benign concentric annular macular dystrophy].

In routine eye examination of a 32-year-old male patient an annular macular dystrophy was noted in absence of distinctive visual complaints. Visual acuity was 20/20, the photopic and scotopic electroretinograms were normal. The ring scotoma in perimetry and the macula finding in ophthalmoscopy corresponded to the fluorescein angiographic pattern. Color vision deficiency was only mild without any predominant axis of confusion. Benign concentric annular macular dystrophy is rarely described in literature. Differential diagnosis includes all 'bull's eye' conditions.

Adult↗
PubMed1994

[Differential diagnosis of cone dystrophies].

Electrophysiological and psychophysical findings recorded in 70 patients with three hereditary diseases of the cone system,--blue cone monochromatism, cone-rod dystrophy and selective cone dystrophy--were compared. Blue cone monochromatism is distinguished from the other two diseases by a reduction of visual acuity since childhood, without progression and with a sex-linked mode of inheritance. In addition, nystagmus is generally observed only in the time shortly after birth and the green and red cones are found to be missing on spectral sensitivity measurements. Cone-rod dystrophy can be distinguished from the blue cone monochromatism by a reduction in visual acuity later in life with progression of the symptoms. Spectral sensitivity measurements reveal reduced function of all three cones in cone-rod dystrophy and a single cone mechanism in selective cone dystrophy. Moreover, in cone-rod dystrophy the ERG reveals a reduction in the amplitudes of the photopic system and often mild involvement of the scotopic part. Measurement of the spectral sensitivity and the ERG can thus help in the diagnosis of these three hereditary diseases.

Color Perception↗
PubMed1993

Antagonism of the non-opioid component of ethanol-induced analgesia by the NMDA receptor antagonist MK-801.

Recent evidence from our laboratory suggests that the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) selectively antagonizes non-opioid (i.e. naloxone-insensitive) mechanisms of stress-induced analgesia in mice. For example, we have recently demonstrated that a low dose of MK-801 (0.075 mg/kg, i.p.) antagonizes the non-opioid component of a mixed opioid/non-opioid swim stress-induced analgesia (SSIA) resulting from forced swimming for 3 min in 20 degrees C water. Since ethanol-induced analgesia (EIA) has been found to be only partially attenuated by naloxone, we hypothesized that MK-801 would similarly block the non-opioid component of EIA. The effects of MK-801 and of the opioid receptor antagonist naloxone (10 mg/kg, i.p.) on analgesia produced by ethanol (2.5 g/kg in 20% vol/vol, i.p.) were studied in control mice and in mice selectively bred for high (HA) or low (LA) SSIA. HA mice showed significantly more, and LA mice significantly less, EIA than controls. Naloxone and MK-801 significantly attenuated EIA in control and HA mice, and in these lines the combined administration of both antagonists blocked EIA completely. In LA mice, which displayed very little EIA, naloxone but not MK-801 reversed EIA completely. These findings provide additional evidence for the role of the NMDA receptor in non-opioid mechanisms of analgesia. The finding that mice selectively bred for high and low SSIA, also display high and low EIA suggests common mediation of the effects of stress and ethanol on antinociceptive processes.

Analgesia↗
PubMed1993

Cross-tolerance between morphine and swim analgesia in mice selectively bred for high and low stress-induced analgesia.

Mice selectively bred for high (HA) and for low analgesia (LA) induced by 3-min swimming at 20 degrees C and unselected controls (C) were injected three times daily for 3 days with 20 mg/kg morphine HCl. The analgesic effect of 10 mg/kg morphine in nontolerant mice differed between the lines in the rank order of HA > C > LA and significantly decreased after repeated treatment with morphine, as revealed by the hotplate test (56 degrees C). The tolerance to morphine analgesia was more pronounced in HA than in C mice but did not develop at all in LA mice. Similarly, the magnitude of swim-induced analgesia in morphine tolerant mice decreased to a greater degree in the HA than the C line but did not change in LA mice. Naloxone HCl (1 and 10 mg/kg) attenuated swim analgesia more in nontolerant HA than C mice but had no effect in morphine-tolerant HA and C and in all LA mice. The differential degree of morphine tolerance and cross-tolerance with swim analgesia suggests that the strategy of selective breeding toward divergent magnitudes of stress-induced analgesia has differentiated opioid involvement in endogenous pain inhibition in the selected lines.

Analgesia↗
PubMed1993

Genetic heterogeneity among blue-cone monochromats.

Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.

Base Sequence↗
PubMed1991

Tolerance and cross-tolerance with morphine in mice selectively bred for high and low stress-induced analgesia.

Mice selectively bred for high (HA) and low (LA) swim-induced analgesia were exposed to two different stress paradigms; one consisting of a 3-min swim at 20 degrees C daily for 14 days, and the other consisting of 3-min swims repeated at 2-h intervals for 48 h. Both forms of chronic stress resulted in the development of tolerance to swim-induced antinociception to a greater degree in the HA mice than in control (C) mice, but were both ineffective at inducing tolerance in LA mice. Swimming repeated at 2-h intervals for 48 h resulted in cross-tolerance with morphine in HA and C mice. Naloxone (1 and 10 mg/kg, IP) failed to antagonize swim-induced analgesia in mice that had experienced chronic swimming in the 2-h/48-h paradigm. The daily swimming paradigm failed to produce cross-tolerance with morphine analgesia in any line. Differential degree of tolerance in three lines supports a hypothesis that selective breeding for high and low stress-induced analgesia has modified the degree of opioid involvement in the endogenous analgesia mechanisms.

Animals↗
PubMed1990

Potentiation of swim analgesia by D-amino acids in mice is genotype dependent.

The effect of combined treatment with 125 mg/kg of D-phenylalanine plus 125 mg/kg of D-leucine (IP) on magnitude and duration of analgesia caused by 3 min swim at 20 degrees C was studied in mouse lines selectively bred for 20 generations toward high and low level of stress-induced analgesia. The D-amino acids administered 30 min prior to swimming increased postswim tail-flick latencies and prolonged antinociception more in the high analgesia line (HA) than in concomitantly bred unselected controls, but were not effective in the low analgesia line (LA). The potentiation of swim analgesia by D-amino acids was prevented by simultaneous administration of 1 mg/kg of naloxone hydrochloride which, given alone, antagonized the analgesia more in the HA line than in controls, but not in the LA line. The results are interpreted in terms of genetic differentiation of opioidergic transmission in the selectively bred mouse lines.

Amino Acids↗
PubMed1990

Correlation between magnitude and opioid mediation of stress-induced analgesia: individual differences and the effect of selective breeding.

Two experiments were made showing that opioid involvement coincides with the magnitude of stress-induced analgesia. In Experiment I rats subjected to cold water swims were screened for jump threshold levels on electrified grid and divided into high, medium and low threshold responders' groups. Later on the three groups were given 90 s forepaw footshock. Tail-flick latencies rose highest in the high threshold, and lowest in the low threshold responders. This decrease in nociception was counteracted by naloxone more effectively in high than in medium threshold responders, and not all in low threshold responders. In Experiment II mice selectively bred for high (HA) and low (LA) post-stress analgesia swam at 20 and 2 degrees C. Both stressors were followed by an increase in tail-flick latencies in the order of magnitude HA greater than unselected controls greater than LA line. Naloxone attenuated analgesia after both stressors in the HA line, but was ineffective in LA mice. In unselected controls swimming at 20 degrees C caused naloxone-sensitive, and cold water swims naloxone-resistant analgesia. It is concluded that apart from the kind of stressor, inborn properties of an individual are essential for the development of opioid vs. non-opioid form of post-stress analgesia.

Animals↗
PubMed1988

Difference in escaping electric footshock by genetic mouse lines selectively bred for divergent levels of swim-induced analgesia.

Inbred mouse lines selectively bred for divergent levels of swim induced analgesia were differed in the ability to escape electric footshock. Mice displaying a high analgesia on a hot plate, after swimming for 3 min at 20 degrees centigrade terminated electric current applied at ascending intensity to the grid floor at a higher value compared to the low analgesia line. The difference was particularly pronounced after swim stress, when mice of the former line manifested a serious escape deficit by failing to terminate electric current elikiting apparently aversive phenomena, such as vocalization, runing and jumping. This escape deficit was reserved by naloxone, an opioid antagonist. Results are interpreted in terms of an assumed amnesic effect of endogenous peptides released under the conditions of swim stress. Such interpretation is justified by the data indicating a greater opioid involvement in the swim analgesia in the high analgesia line, compared to low analgesia mice, in which non-opioid mechanisms prevail.

Analgesia↗
PubMed1987

Adrenalectomy and dexamethasone differentially affect postswim antinociception in mice selectively bred for high and low stress-induced analgesia.

The effects of dexamethasone and naloxone on analgesia induced by swimming (3 min, 20 degrees C) were studied in the 6th and 7th generations of adrenalectomized and intact mice selectively bred for high (HA) and low (LA) postswim analgesia. Swim-induced analgesia in intact HA animals was significantly reduced by naloxone and dexamethasone while in LA mice these two compounds were ineffective. Naloxone ability to reverse adrenalectomy-caused swim analgesia increase was much greater in HA than in LA mice. In both intact and adrenalectomized HA animals dexamethasone and naloxone decreased postswim analgesia to the level observed in LA mice. It is suggested that selective breeding for high and low swim analgesia modified the extent of pituitary-adrenal axis involvement in the generation of stress-induced analgesia.

Adrenalectomy↗