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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 199 records · Page 11Linked to original sources

Ca(2+)-related hepatocellular alterations during intra-abdominal sepsis.

Intra-abdominal sepsis was induced in rats by implanting into their abdominal cavities fecal-agar pellets impregnated with Escherichia coli and Bacteroides fragilis. Sham-operated rats received sterile pellets. A group of sterile- and septic-implanted rats was treated intraperitoneally with diltiazem (1.2 mg/kg) 8 h after implantations. Septic- and sterile-implanted rat hepatocytes were loaded with 1) the fluorescent dye indo-1 to quantify hepatocyte basal and vasopressin (100 nM)-elevated cytosolic Ca2+ concentration and 2) 45Ca to quantify Ca2+ flux and cellular content of exchangeable Ca2+. Lipid peroxidation was determined by measuring conjugated dienes (CD) and thiobarbiturate-reactive substances (TBA-RS) in liver homogenates. In septic-implanted rats, the basal cytosolic [Ca2+], cellular exchangeable Ca2+, Ca2+ flux, CD, and TBA-RS were significantly higher than in sterile-implanted rats. Although vasopressin caused a significant elevation in cytosolic [Ca2+] in septic rat hepatocytes, the magnitude of this elevation was significantly smaller than that found in the sterile group. Diltiazem treatment of septic rats significantly decreased basal cytosolic [Ca2+], cellular exchangeable Ca2+ content, Ca2+ flux, CD, and TBA-RS. Also, vasopressin-induced increase in hepatocyte cytosolic [Ca2+] in diltiazem-treated septic rats was significantly greater than that observed in untreated septic rats. Both Ca2+ and membrane lipid alterations were attenuated with diltiazem treatment of septic rats. These results suggest that prevention or attenuation of Ca2+ channel-mediated Ca2+ influx restores both Ca2+ homeostasis and membrane lipid alteration.

Abdomen↗

[A simple method for repositioning metatarsal fractures].

Because of small direct contact to the fracture fragments reduction of metatarsal fractures can be achieved only indirectly by applying traction to the toes. In this article a method for simple direct manipulation of the distal main fragment of metatarsal fractures is described: A K-wire is drilled in dorsi plantar direction across the head of the fractured metatarsal and mounted on a traction bow. In this manner the distal fracture fragment can be moved in all directions and placed exactly onto the proximal fragment. All 8 patients with multiple metatarsal fractures could be treated by closed reduction and percutaneous pinning. The described method allows simple and precise reduction of metatarsal fractures, reduced x-ray exposure of the surgeon's hand by short operation times, and manipulation for fracture reduction outside the x-ray beam.

Bone Wires↗

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP.

Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5-2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical parameters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met5]-enkephalin, [Leu5]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met5]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu5]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met5]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Cocaethylene is more potent than cocaine in mediating lethality.

Cocaethylene is a pharmacologically active cocaine metabolite that is formed in the presence of ethanol by the activity of liver enzymes. The pharmacology of cocaethylene has not been extensively investigated and its acute toxicity is unknown. The acute toxicity of cocaethylene was compared to cocaine in Swiss-Webster mice. The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.

Animals↗

Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter.

Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse.

Adult↗

Peripheral pharmacokinetic handling and metabolism of L-dopa in the rat: the effect of route of administration and carbidopa pretreatment.

The effect of carbidopa (L-alpha-methyldopa hydrazine; 25 mg kg-1 i.p.) pretreatment on the pharmacokinetics and peripheral metabolism of orally and intra-aortically administered L-3,4-dihydroxyphenylalanine (L-dopa; 50 mg kg-1) has been examined in rats. Following intra-aortic (i.a.) administration, plasma levels of the drug declined biexponentially. Pretreatment with carbidopa resulted in higher plasma concentrations after i.a. administration of L-dopa, but had no effect on the half-life (t1/2) for its distribution or elimination. Oral L-dopa gave peak plasma concentrations at 1.5 h and then a log-linear decline between 1.5 and 6 h. Pretreatment with carbidopa also produced higher plasma concentrations of L-dopa given orally, and the t1/2 for its elimination tended to be increased compared with values achieved after the drug alone. Pretreatment with carbidopa decreased volume of distribution and total plasma clearance and increased area under the curve (0-infinity) after L-dopa i.a. and increased AUC0-infinity after L-dopa p.o. The fraction of the oral dose absorbed through the gut was not affected. Carbidopa pretreatment enhanced the accumulation of 3-O-methyldopa and decreased dopamine levels in plasma after both i.a. and oral administration of L-dopa. Higher plasma concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid (HVA) were detected in the plasma after i.a. rather than oral administration of L-dopa and pretreatment with carbidopa greatly reduced these plasma concentrations. However, following oral L-dopa, only HVA levels were reduced by carbidopa pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

An investigation of parents' attitudes and the communication skills of their deaf children.

The reciprocity and consequences of parent-child interactions are an important subject of inquiry in child development literature. The majority of studies on deaf children with hearing parents focus on differences in parent-child interactions, which emanate from a number of factors including parental attitudes toward deafness and acceptance of alternative modes of communication. The purpose of this study was to investigate the relationship between parental attitudes toward deafness and the communication skills of their hearing-impaired children. Whereas the majority of researchers in interactional studies have focused on mothers, both parents were included in this investigation. Significant correlations were found between fathers' scores on the Attitude to Deafness Scale and the language comprehension scores of their deaf children. No significant differences in attitudes were found between mothers and fathers. Similarly, no significant differences were found between the parents of boys and the parents of girls.

Adult↗

Comparison of different prothrombin complex concentrates--in vitro and in vivo studies.

The potency and tests for thrombogenicity were studied prospectively in 7 different (two lots of each brand, A-G) prothrombin complex concentrates (PCC). Human albumine (H) and a factor IX concentrate (I), served as controls. The potency of coagulation factors and inhibitors varied considerably. Two brands (E, F) contained no protein S, additionally one brand contained no protein C. Two preparations exhibited high amidolytic activities, especially towards the thrombin-sensitive chromogenic substrate S-2238, in vitro. These activities could be quenched in part by the addition of hirudin or antithrombin III. The heparin and antithrombin III content of the PCCs was significantly different, and, after addition of antithrombin III an increase of thrombin-antithrombin III complexes in 2 preparations (B, D) was observed in vitro. Additionally, three brands (B, D, F) caused more severe cardio-pulmonary reactions in rabbits, associated with an increase of fibrin split products for brands B and D. We conclude that the use of these preparations in patients, in whom an acquired protein C or S defect, or a hypercoagulable state, can be suspected, cannot be recommended.

Animals↗

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset.

Four adult marmosets were treated with increasing doses of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) in the range 0.23-4.3 mg/kg i.p. to give a cumulative dose of 11.0-11.6 mg/kg over a 6-10 day period. After 4 days of treatment, and as the dosage was gradually increased, the animals exhibited mild motor deficits. These abnormalities slowly declined over the following 1-6 week period. In contrast, similar treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 3-5 days in a cumulative dose of 6.9-9.2 mg/kg produced gross impairment of motor function which persisted throughout the 5 weeks period of observation. Administration of 2'-methyl-MPTP for 6-10 days caused some decrease in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), but not homovanillic acid (HVA) content in the caudate nucleus in animals 5-6 weeks after the start of treatment. There was a small decrease in [3H]dopamine uptake into putamen synaptosomes. This contrasted with the marked decreases in all these parameters observed after MPTP treatment of common marmosets. Histological examination of the substantia nigra from the four animals treated with 2'-methyl-MPTP did not show degeneration or loss of dopamine-containing cell bodies in the zona compacta. In contrast, MPTP caused severe destruction of these pigmented nigral neurones. In the common marmoset 2'-methyl-MPTP does not appear to show the same neurotoxic action as MPTP itself. This contrasts with findings in the mouse where 2'-methyl-MPTP is more toxic to dopamine-containing cells of substantia nigra than MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Three tomato genes code for heat stress transcription factors with a region of remarkable homology to the DNA-binding domain of the yeast HSF.

Heat stress (hs) treatment of cell cultures of Lycopersicon peruvianum (Lp, tomato) results in activation of preformed transcription factor(s) (HSF) binding to the heat stress consensus element (HSE). Using appropriate synthetic HSE oligonucleotides, three types of clones with potential HSE binding domains were isolated from a tomato lambda gt11 expression library by DNA-ligand screening. One of the potential HSF genes is constitutively expressed, the other two are hs-induced. Sequence comparison defines a single domain of approximately 90 amino acid residues common to all three genes and to the HSE--binding domain of the yeast HSF. The domain is flanked by proline residues and characterized by two long overlapping repeats. We speculate that the derived consensus sequence is also representative for other eukaryotic HSF and that the existence of several different HSF is not unique to plants.

Amino Acid Sequence↗

Percutaneous absorption of benzyl acetate through rat skin in vitro. 1. Validation of an in vitro model against in vivo data.

The percutaneous absorption in vitro of the fragrance agent benzyl acetate has been evaluated in flow-through diffusion cells using shaved full-thickness skin from male Fischer 344 rats. After the application of neat [methylene-14C]benzyl acetate to the epidermal surface of the skin and occlusion with parafilm 1.3 cm above the skin surface, the absorption of the chemical across the skin and into the receptor fluid was rapid and extensive, commencing within 1 hr of application, and reaching 49.8 +/- 3.2% (mean +/- SD, n = 4) of the applied dose after 48 hr. The coefficient of variation for absorption at 48 hr between four identical experiments was 6.4%. The extent of absorption at 48 hr of benzyl acetate applied in 50% (v/v) ethanol was not significantly different from that after application neat, although absorption at earlier times was enhanced, with a maximum increase of 8.5% of the applied dose at 12 hr. Over the dose range studied there was a linear relationship (r = 0.996) between the amount of benzyl acetate applied to the skin (1.66-33.13 mg benzyl acetate/cm2) and the amount absorbed into the receptor fluid at 24 hr (0.66 +/- 0.04-10.27 +/- 0.51 mg/cm2). The extent of absorption of benzyl acetate through rat skin in vitro was compared with the extent of absorption in vivo at 24 hr and a correlation coefficient of 0.993 was obtained. These data support the use of this in vitro system as a model to predict in vivo absorption and indicate the suitability of the system to study factors influencing the disposition of topically applied benzyl acetate.

Animals↗

[Quality control of prothrombin complex preparations: in vivo and in vitro findings].

Prothrombin complex concentrates (PCC) are frequently used for the treatment of acquired coagulation factor deficiencies. However, a major problem when using these preparations is their thrombogenic potential. Thus, the potency and tests for thrombogenicity were studied prospectively in 7 different PCC's. Human albumine and a factor IX concentrate served as controls. The potency of coagulation factors and inhibitors varied considerably, especially for proteins S and C. Two preparations exhibited high amidolytic activities in vitro. These activities could be quenched in part by the addition of hirudin or antithrombin III. Additionally, these two preparations caused more severe cardiopulmonary reactions in rabbits and an increase of fibrin split products. We conclude that the use of these preparations in patients, in whom an acquired protein C or S defect, or a hypercoagulable state, can be suspected, cannot be recommended.

Blood Coagulation Factors↗

Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets.

Acute treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused an initial profound akinesia and other motor deficits. However, over the following months akinesia gradually disappeared although the animals remained clumsy and poorly coordinated. At 10 days following MPTP treatment there was a profound decrease in the dopamine, HVA and DOPAC content of the caudate nucleus, putamen and nucleus accumbens. By 3-4 months following MPTP treatment the animals had largely recovered from their akinesia, but the caudate nucleus and putamen dopamine, HVA and DOPAC content remained low. In contrast, the dopamine content of the nucleus accumbens had returned towards normal and the metabolite levels were higher than at 10 days. No overall alterations in 5HT or 5HIAA levels were observed at either time point. The transient and reversible nature of dopamine loss in the nucleus accumbens may contribute to the initial profound akinesia exhibited by common marmosets treated with MPTP. The restoration of dopamine levels in the nucleus accumbens may be partially responsible for the subsequent recovery of motor function that occurs in MPTP-treated marmosets.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗