Biomedical subjects

A Lang

Publications and source records attributed to A Lang.

At least 19 recordsLinked to original sources

PubMed1995

Beneficial effects of co-administration of catechol-O-methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression.

The administration of catechol-O-methyltransferase inhibitors alone changed neither the behavior of the rats in two animal models of depression, the forced swimming test (entacapone and tolcapone) or in the learned helplessness paradigm (tolcapone), nor the locomotor activity. L-Dihydroxyphenylalanine (L-DOPA) and carbidopa treatment as such decreased motility but did not improve the behavior in the antidepressant tests. Co-administration of catechol-O-methyltransferase inhibitors and L-DOPA/carbidopa increased the performance of rats in both tests without increasing locomotor activity. Catechol-O-methyltransferase inhibitors could be beneficial as adjunct drugs of L-DOPA not only in Parkinson's disease but also in the coincident depressive illness.

Analysis of Variance↗

PubMed1995

Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats.

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1995

Further studies on the role of cholecystokinin-A and B receptors in secretion of anterior pituitary hormones in male rats.

We compared the effects of unselective cholecystokinin (CCK) agonists (caerulein and CCK-8s) and a CCKB agonist CCK-4 on the secretion of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) in male rats. The subcutaneous (s.c.) administration of caerulein and CCK-8s suppressed dose-dependently TSH and GH levels. In contrast, when given into the 3rd brain ventricle (i.c.v.) caerulein dose-dependently elevated the GH levels. Next the importance of the afferent vagal nerves was studied in the action of caerulein and CCK-4. Subdiaphragmatic vagotomy itself decreased cold-stimulated TSH levels but abolished the suppressing effect of intraperitoneal (i.p.), and apparently also that of the i.c.v. caerulein. GH and PRL levels were altered neither by vagotomy nor caerulein. CCK-4 did not affect hormone levels. Atropine and butylscopolamine (i.p.) themselves did not alter TSH, PRL or GH secretion in intact rats. Neither did they reverse the effect of caerulein on TSH. In conclusion, CCKA receptors dominate in TSH and CCKB receptors in GH regulation. CCKA receptors in the gastrointestinal tract, related to the nervus vagus are mediating the inhibitory effect of caerulein upon TSH secretion but inhibition of GH secretion does not depend on the nervus vagus. CCKB receptors in the brain stem or near the 3rd brain ventricle are responsible for stimulation of GH secretion.

Animals↗

PubMed1995

Effect of silicone sound speed and intraocular lens thickness on pseudophakic axial length corrections.

We compared the sound speeds of SLM-1/UV (990 M/sec at 35 degrees Celsius [degrees C]), SLM-2/UV (1090 M/sec at 35 degrees C), and Perspex CQ poly(methyl methacrylate)(2658 M/sec at 35 degrees C). Methods are presented to determine the correction of axial length (CAL) factors for axial length measurements made on pseudophakes with AMO PhacoFlex Si-18, Si-26 (SLM-1/UV), and AMO PhacoFlex II SI-20 or SI-30 (SLM-2/UV) silicone intraocular lenses (IOLs). A CAL is required to avoid potential errors with secondary IOL power predictions; CALs, which are strongly dependent on the material sound speed and less so on lens thickness, ranged from -0.65 mm to -1.20 mm for SLM-1/UV silicone IOLs and from -0.35 mm to -0.55 mm for SLM-2/UV silicone IOLs. The sound speeds of IOL materials varied insignificantly between ambient room temperature (23 degrees C) and intraocular temperature (35 degrees C).

Artifacts↗

PubMed1995

Cathepsin B in osteoarthritis: zonal variation of enzyme activity in human femoral head cartilage.

OBJECTIVES: To determine the quantitative topographical distribution of cathepsin B in human femoral head cartilage by measuring the zonal variation of enzyme activity in specimens taken from various anatomical regions of normal and osteoarthritic (OA) tissues, and to correlate this parameter with the severity of the OA lesions. METHODS: OA articular cartilage was obtained at surgery for total hip replacement and control cartilage obtained at postmortem. Cylinders of full thickness cartilage with underlying bone were retrieved with a biopsy trephine. Sections of cartilage were produced by cryocutting the tissue as slices parallel to the articular surface and assayed for cathepsin B with a specific, highly sensitive fluorogenic substrate. The severity of the OA lesions was graded according to the histopathological-histochemical method of Mankin. RESULTS: Zonal cathepsin B activity of normal cartilage was uniform and low in all regions of the femoral head. In apparently intact OA cartilage and in severely degraded tissue the zonal distribution and the amounts of enzyme were similar to control values. At sites with active disease, cathepsin B activity was much greater than in controls and its irregular zonal distribution correlated with tissue degeneration, hypercellularity, or cloning of chondrocytes as determined histochemically. Particularly high enzyme levels were observed at sites with regenerating cartilage, where some zonal peaks attained 20-fold activity with respect to controls. CONCLUSION: Cathepsin B may play a role in sustaining the chronicity of OA, not as an initiator, but rather as a perpetuator of the disease and as an antagonist of regeneration.

Adult↗

PubMed1995

Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage.

OBJECTIVE: To localise the cysteine endopeptidase cathepsin B in chondrocytes and cartilage from normal and osteoarthritic (OA) human femoral heads in order to provide qualitative information on its cellular expression and distribution at possible sites of action. METHODS: OA articular cartilage was obtained at surgery for total hip replacement; control cartilage was obtained at postmortem. Chondrocytes were isolated by sequential enzymatic digestion and cathepsin B analysed by immunocytochemistry and activity staining with a fluorogenic substrate. Lysosomes were visualised by fluorescence microscopy after staining of living cells with acridine orange. Using a histochemical reaction, enzyme activity was measured in cryosections of full thickness cartilage. RESULTS: Chondrocytes from normal cartilage contained very few lysosomes and only a minor cell population was cathepsin B positive. A high proportion of chondrocytes from active OA cartilage contained a large number of lysosomes and an excess of cathepsin B in intracellular organelles; the enzyme was stored in an active form. In this respect, OA chondrocytes closely resembled normal cells that had been phenotypically modulated by serial subcultures. No cathepsin B activity could be detected by histochemistry in either chondrocytes or matrix of normal cartilage. While apparently intact and severely degraded OA cartilage was also cathepsin B negative, tissue at sites of active destruction and, particularly, at repair sites was highly positive. CONCLUSION: The presence and the particular distribution of active cathepsin B in OA cartilage at 'more involved' sites suggest a pathological role for this enzyme in sustaining and perpetuating cartilage degradation. While other stimuli may also be responsible for cathepsin B expression in OA chondrocytes, the similarity with artificially modulated cells indicates fibroblastic metaplasia as a plausible mechanism.

Adult↗

PubMed1995

Cold exposure attenuates effects of secretagogues on serum prolactin and growth hormone levels in male rats.

The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint stress on prolactin and growth hormone (GH) secretion was compared during cold exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats. Rectal temperature was also measured. The stimulatory effect of morphine, dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin release induced by pimozide and restraint stress. Cold exposure also antagonized the effect of morphine and dexmedetomidine on GH secretion. The stimulatory effect of morphine on prolactin and GH secretion was restored in the warm environment despite the sustained hypothermia. Cold exposure blocked the stimulatory effect of morphine on prolactin secretion in rats that were tolerant to the hypothermic effect of morphine. Thus hypothermia caused by morphine, dexmedetomidine, and m-CPP during cold exposure is not the sole factor in the antagonistic effect of cold. We suggest that cold exposure releases some compound(s) modulating hypothalamic neural pathways.

Animals↗

PubMed1995

Prolonged generalized pruritus associated with selective elevation of IgA as the presenting symptoms of sarcoidosis.

OBJECTIVE: The purpose of this case report is to describe the possible initial presentation of sarcoidosis as generalized prolonged pruritus. METHODS: In a patient presenting with prolonged generalized pruritus who also had selective elevation of IgA, the diagnosis of sarcoidosis was confirmed by bilateral interstitial infiltrates on chest radiograph, elevated angiotensin-converting enzyme, and dermal granuloma on skin biopsy from a recent rash. CONCLUSION: Sarcoidosis should be added to the list of diseases associated with prolonged pruritus and routine chest radiographs should be obtained in these patients.

Granuloma↗

PubMed1994

Opposite effects mediated by CCKA and CCKB receptors in behavioural and hormonal studies in rats.

We compared the influence of two cholecystokinin (CCK) antagonists, devazepide and L-365,260 [3R-(+)-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3y l)-N'-(3-methyl-phenyl)urea], upon two distinct phenomena, behavioural and hormonal effects of caerulein (5 micrograms/kg s.c.), and unselective CCK agonist, in rats. Behavioural effects were assessed in the elevated plus-maze and open field tests. In separate experiments, effects on thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) levels in serum of male rats were studied. Caerulein inhibited the exploratory behaviour in the plus-maze. Time spent in the open part, the number of line crossings and closed arm entries were significantly decreased, whereas the ratio of failed attempts/closed arm entries was increased. The anti-exploratory effect of caerulein was antagonized by the pretreatment with L-365,260 (10 micrograms/kg), a preferential antagonist at CCKB receptors, but was increased by devazepide (1-100 micrograms/kg), a preferential CCKA antagonist. L-365,260 (1-100 micrograms/kg) and devazepide (1-100 micrograms/kg) given alone did not change the behaviour of rats in the plus-maze test. Caerulein (5 micrograms/kg) itself did not modify the locomotor activity of rats in open field. However, the concomitant administration of caerulein with devazepide (1-10 micrograms/kg) reduced the frequency of line crossings and rearings. In the hormonal studies caerulein significantly decreased the cold-induced increase of TSH levels in serum. GH and PRL levels were not markedly affected by caerulein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Evidence for potentiation by CCK antagonists of the effect of cholecystokinin octapeptide in the elevated plus-maze.

Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 micrograms/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 microgram/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 micrograms/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 micrograms/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect of CCK-8 is related to the suppression of motor activity. This peculiar interaction between CCK-8 and CCK antagonists could be explained in the light of the opposite role of CCKA and CCKB receptors in the regulation of motor activity in mice.

Animals↗

PubMed1994

Subdiaphragmatic vagotomy does not prevent the anti-exploratory effect of caerulein in the elevated plus-maze.

We compared the action of subdiaphragmatic vagotomy upon the anti-exploratory and motor depressant effects of caerulein, an agonist of cholecystokinin (CCK) receptors, in male rats. Vagotomized rats entered more frequently into the open arms of elevated plus-maze compared to intact control rats. Caerulein (1 microgram/kg subcutaneously (s.c.)) significantly suppressed the exploratory behaviour in vagotomized rats but not in intact and sham-operated rats. In contrast, subdiaphragmatic vagotomy did not change the locomotor activity of rats in open field compared to intact and sham-operated animals. At a higher dose (10 micrograms/kg s.c.), the caerulein pretreatment markedly decreased the number of line crossings, rearings and head-dippings of intact animals in open field. In sham-operated rats caerulein also suppressed the locomotor activity, whereas in vagotomized rats it only tended to reduce the frequency of rearings. Consequently, the present study revealed the different action of vagotomy upon the motor depressant and anti-exploratory effects of caerulein. These results support the view that CCKA receptors in the gastrointestinal tract are mediating the motor depressant, whereas CCKB receptors in the brainstem are involved into the mediation of anti-exploratory effect of caerulein.

Animals↗

PubMed1994

A new versatile system for freeze-substitution, freeze-drying and low temperature embedding of biological specimens.

A universal system for freeze-substitution (FS), freeze-drying (FD) and low temperature embedding (LTE) has been developed, suited to perform standardized procedures of cryoprocessing biological and medical specimens as well as systematic studies of dehydration and embedding at various low and high temperatures. In a 35 1 Dewar vessel with 110 mm neck diameter an aluminum tube is mounted to the bottom of the liquid nitrogen (LN2x) reservoir and extends to the lower part of the cylindrical neck. At its top an aluminum plate serves as a contact surface for either the FS chamber or the FD chamber. Fs and subsequent LTE are carried out in an environment of dry cold nitrogen gas provided by evaporating nitrogen from the dewar. Different capsules and moulds may be used for cryodehydration and LTE. FD of bulk specimens or cryosections takes place in an absolutely clean vacuum provided by a cryosorption pump integrated in the FD apparatus. Most of the H2O molecules from the frozen specimen are trapped by large cold surfaces inside the drying chamber. Due to the low LN2 consumption during FS or FD (3-4 1 LN2/day) both procedures may be carried out for 8-10 days without refilling the dewar. A few representative results show that well frozen biological material is stabilized by prolonged FS or FD at temperatures of about -80 degrees C without user of chemical fixatives like OsO4 in the substitution medium during FS or by OsO4 vapor fixation after FD.

Animals↗

PubMed1993

Factors influencing physiological variations in the activity of the Rous sarcoma virus long terminal repeat.

Previous reports have shown that Rous sarcoma virus (RSV) transcript levels in mammalian cells can be elevated by serum treatment and cellular transformation. To understand this, we have examined how the RSV long terminal repeat (LTR) enhancer is affected by cellular growth state in clonally related normal and RSV-infected Rat-1 cell lines. Functional assays with enhancer mutants have shown that two LTR CArG motifs and a CCAAT box have individual and combinatorial effects on basal LTR activity, but only the CArG elements contribute to serum responses in phenotypically normal cells. Augmented enhancer activity in transformed cells is mediated in part by these CArG motifs, which under these conditions are not further stimulable by serum. Protein binding to the CArG and CCAAT elements corresponds with functional variations, binding proteins being scarce in serum-deprived normal cells and enhanced by serum stimulation, cellular transformation and, in part, cellular density. These findings provide an explanation for physiologically dependent fluctuations in RSV expression, which may include the initiation of the proviral transcriptional repression that is frequently observed in mammalian hosts. However, we also show that transcript levels of some integrated proviruses are independent of variations in the cell's ability to support LTR activity, showing that the site of insertion can be of overriding importance in determining proviral expression.

Animals↗

PubMed1993

Social isolation of rats increases the density of cholecystokinin receptors in the frontal cortex and abolishes the anti-exploratory effect of caerulein.

The role of cholecystokinin (CCK) receptors in the development of anxiety caused by social isolation of rats was studied using the elevated plus-maze and receptor binding techniques. The isolation of male Wistar rats significantly reduced their exploratory activity in the elevated plus-maze compared with that of rats kept in groups of four. Caerulein (0.1-5 micrograms/kg s.c.), an agonist at CCK receptors, only at the highest dose (5 micrograms/kg) significantly decreased the exploratory behaviour of rats housed in groups, but not in the isolated rats. By contrast, small doses of caerulein (0.1-0.5 microgram/kg) even tended to increase the behavioural activity of isolated rats in the plus-maze test. In parallel to the behavioural changes, isolation of the rats increased the number of [3H]pCCK-8 binding sites in the frontal cortex, but not in the other forebrain structures (the mesolimbic area, striatum and hippocampus). Isolation did not affect the density of benzodiazepine receptors in the frontal cortex. In conclusion, the isolation of rats for 7 days produced anxiogenic-like effect on the behaviour of rats and increased the number of CCK receptors in the frontal cortex without affecting benzodiazepine receptors.

Animals↗

PubMed1993

Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside.

Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-alpha-2c treatment for at least two months were entered in the present pilot study. IFN-alpha treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m2/day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/l, the Ara-C dose was increased to 20 mg/m2/day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-alpha/Ara-C cycles (3-14/patient). Five patients received 1-5 cycles with Ara-C dose intensification to 20 mg/m2/day. The following gastrointestinal and hematological toxicities were attributable to Ara-C, as they had not been observed in these patients during the preceding IFN-alpha monotherapy period. Gastrointestinal side effects consisted of nausea grade 1 (n = 5) and diarrhea grade 2 (n = 1). Hematotoxicity was observed in eight patients, grade 1 in five patients and grades 2, 3 and 4 in one of the patients each. Both episodes of grades 3 and 4 toxicity were seen during dose escalation to 20 mg/m2. Small cytogenetic responses (4-14%) were observed in 3 patients and a larger one (50%) in one patient, hematological improvement or stable disease in an additional three patients. These preliminary data suggest that the combination of IFN-alpha and low-dose Ara-C is active in inducing cytogenetic responses in CML patients at an acceptable rate of toxicity and therefore warrant further investigation.

Adult↗

PubMed1993

Anti-exploratory effect of N-methyl-D-aspartate in elevated plus-maze. Involvement of NMDA and CCK receptors.

N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open parts of an elevated plus-maze. Paradoxically, 40 mg/kg NMDA did not modify the behavior of the mice in the plus-maze. NMDA at a dose of 80 mg/kg again depressed the exploratory activity of mice, but this effect was accompanied with tremor and compulsive tail biting. The 'anti-exploratory' dose of NMDA (20 mg/kg) increased, whereas the 'tremorigenic' dose (80 mg/kg) significantly decreased the number of cholecystokinin (CCK) binding sites in the mouse cerebral cortex. The competitive NMDA antagonist (+/-)-CPP (2.5-5 mg/kg) and the non-competitive antagonist MK-801 (0.25 mg/kg) antagonized the anti-exploratory effect of NMDA (20 mg/kg). The tricyclic antidepressant imipramine (5 mg/kg, but not 1 or 10 mg/kg) also attenuated the inhibition of exploratory activity induced by NMDA. Of three CCK receptor antagonists tested, the unselective CCK antagonist proglumide (1 mg/kg, but not 0.1 and 10 mg/kg) significantly opposed the anti-exploratory action of NMDA. The selective CCK antagonists L-365,260 (1 microgram/kg) and devazepide (1 microgram/kg) were evidently weaker antagonists of NMDA. Furthermore, 10 micrograms/kg of L-365,260, a CCK-B receptor antagonist, and 1 mg/kg of devazepide, a CCK-A receptor antagonist, even tended to augment the effect of NMDA in the plus-maze. The results of the present study seem to give some support to the notion that not only NMDA receptors, but also CCK-ergic mechanisms are involved in the modulation of anti-exploratory action of NMDA in the elevated plus-maze.

Analysis of Variance↗

PubMed1993

Comparison of the optical and visual quality of poly(methyl methacrylate) and silicone intraocular lenses.

We evaluated experimentally the optical quality of poly(methyl methacrylate) (PMMA) (Storz 68UV, AMO PC58) and silicone (AMO SI19, Adatomed 90D) intraocular lenses (IOLs) and compared the results with our clinical data. We measured surface and image quality using the Zygo laser interferometer and modulation transfer function (MTF) using the Ealing EROS MTF analyzer. Contrast acuity was tested clinically with glare and without glare (Regan charts); AMO PC58, n = 18; AMO SI19, n = 7; Adatomed 90D, n = 18). Modulation transfer function and image quality were slightly better with PMMA IOLs but the reduction of MTF with silicone lenses was within the 1/8 diopter defocus range. Surface quality of silicone IOLs was superior to that of PMMA IOLs. Contrast acuity measured clinically was also slightly better with PMMA IOLs at low contrast and with glare but differences were not significant. Our results suggest that optical and visual quality of silicone IOLs is slightly lower than with PMMA IOLs. Experimental and clinical results correlated closely. However, the small differences observed are unlikely to be significant clinically.

Aged↗

PubMed1993

Interpreting multifocal intraocular lens modulation transfer functions.

The optical performance of new multifocal intraocular lens designs is frequently assessed using the modulation transfer function (MTF). We discuss the relationship between the MTF and clinical measures of human visual function, such as threshold visual acuity and contrast sensitivity. Using in vitro MTF measurements of a human eye model containing a multifocal or monofocal intraocular lens, we predict relative changes in acuity and contrast sensitivity and outline the techniques using a simple model of human retinal threshold detection. Specific concepts introduced include the visual acuity graph, predicted visual acuity graph, and predicted contrast sensitivity function.

Contrast Sensitivity↗