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Biomedical subjects

Y Cohen

Publications and source records attributed to Y Cohen.

At least 307 records · Page 17Linked to original sources

Ontogeny of brain monoamines in lean and obese female Zucker rats.

Differences in monoamine and metabolite levels were previously observed between lean and obese 16 week-old female Zucker rats. In order to test whether these variations exist initially in young animals, catecholamines (CA), serotonin (5-HT) and some of their metabolites were assayed in brain areas of Zucker rats between 5 and 16 weeks of age. The levels of most compounds in all areas studied increased with age in both groups. At 5 weeks of age, there was no difference between lean and obese rats. At 8 weeks, a reduction of dopamine (DA) metabolites appeared in the striatum and cortex of obese rats and persisted up to 16 weeks. A reduction of the 5-HT metabolite, 5-hydroxyindolacetic acid (5-HIAA), occurred at 8 weeks only. At 16 weeks, increases of DA and 5-HT in the hypothalamus and decreases of norepinephrine (NE), 5-HT and 5-HIAA in the hippocampus appeared. These data suggest that the development of obesity occurs before any monoamine alterations.

3,4-Dihydroxyphenylacetic Acid↗

Correlations of dose and time-dose-fractionation factors (TDF) with treatment results and side effects in cancer of the uterine cervix.

Treatment results and side effects were analyzed for 57 patients with stage IB-IIIA cancer of the uterine cervix who received external beam radiotherapy combined with intracavitary insertion of cesium-137 sources. The total dosage and time-dose-fractionation (TDF) factors were calculated at point A and at points of maximum exposure in the rectum and bladder. The overall 5-year survival was 62%, and 78% of the complete responders were free of disease at 5 years. A total of 12 patients (21%) developed rectal complications. Two patients (4%) had rectal fibrosis and proctitis; seven cases of rectal bleeding occurred (12%), and 3 patients (5%) developed rectovaginal fistulas. There was no correlation between dose and TDF at point A and treatment failure or appearance of rectal complications. However, the occurrence of radiation damage in the rectum was consistently associated with high values of TDF when they were calculated in the region of maximal exposure in the rectum. The results suggest that TDF may be a useful parameter for predicting radiation damage in combined external beam and intracavitary treatment of cervical cancer.

Female↗

Rat brain monoamine metabolism and hypobaric hypoxia: a new approach.

A chromatographic method with electrochemical detection was used to measure noradrenaline (NA), dopamine (DA), and serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 5-hydroxyindoleacetic acid (5-HIAA) in several brain areas (hypothalamus, hippocampus, striatum and rest of the brain) of rats exposed to a 7000 m simulated altitude for 3 hr. This new direct approach, not using a pharmacological tool, provides further information on the hypobaric hypoxia effects on the main DA and 5-HT metabolic steps. In the hypothalamus, a decreased NA level with increased DA and DOPAC contents was considered as the result of dopamine-beta-hydroxylase activity impairment. The decrease of both 5-HIAA and DOPAC in all brain areas provides further evidence of the hypoxia-induced decrement in MAO activity. Furthermore, in the striatum, it was shown that catechol-O-methyl transferase, up to now considered unaffected by hypoxia, may also be altered by oxygen deficiency.

Animals↗

Variability of changes in obese rat brain monoamines in response to cholecystokinin.

The interactions between cholecystokinin (CCK) and brain monoamines have been investigated. The data found in the literature are quite dissimilar. Several reasons for these disparities have been suggested. We have sought to test some of them, such as the strain of rat, the nutritional state (by the use of two models of obesity), the length of the peptide (CCK 8 and CCK 33), the route of administration (i.p. and i.c.v.) and the time of sacrifice. We indeed found all these experimental conditions to be the cause of differential effects on brain monoamines and metabolites. However, by repeating the same experiments several times, we did not always obtain the same variations, even under the same conditions. In addition to the different parameters tested, another source of variability exists, possibly due to the molecule itself or to seasonal variations.

Animals↗

Dopaminergic metabolism in various rat brain areas after L-dopa loading.

The time course of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 3-methoxytyrosine (3-O-Medopa) concentrations in rat brain after treatment with L-dopa + benserazide has been investigated in the striatum, hypothalamus, hippocampus and cerebellum. These areas were selected for their different dopaminergic activities. After L-dopa loading, DA, DOPAC and HVA were increased in all the structures, but the largest increases were in those tissues with the less dopaminergic activity, while 3-MT increased in the hypothalamus, hippocampus and cerebellum but was lowered in striatum. 3-O-Medopa, which is the direct product of the O-methylation of L-dopa, did not show any specific distribution. The data provide evidence that the striatum, by feed-back mechanisms and specific enzymatic activity, is able to ensure a better regulation of dopaminergic activity than the other structures, thereby overcoming excess L-dopa.

3,4-Dihydroxyphenylacetic Acid↗

Chronic subcutaneous treatment with acebutolol: haemodynamic effects and metabolism in spontaneously hypertensive rats.

Chronic administration of acebutolol (15 mg kg-1 s.c. three times a week for five weeks, then 30 mg kg-1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of beta 2 vascular receptors.

Acebutolol↗

Re-evaluation of the L-dopa loading effect on dopamine metabolism in rat striatum.

Investigation by HPLC with electrochemical detection of dopamine (DA) metabolism in rat striatum after L-dopa + benserazide treatment allowed quantification of the time course evolution of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Furthermore, four peaks which did not appear in controls, were detected in treated striatum. One was identified as 3-methoxytyrosine, the level of which was still high 9 h after treatment. 3-Methoxytyrosine, has been detected previously in plasma of parkinsonian patients treated with L-dopa, and the disturbance in DA metabolism could explain some of the side-effects induced by that treatment.

3,4-Dihydroxyphenylacetic Acid↗

Adaptation to Hydrogen Sulfide of Oxygenic and Anoxygenic Photosynthesis among Cyanobacteria.

Four different types of adaptation to sulfide among cyanobacteria are described based on the differential toxicity to sulfide of photosystems I and II and the capacity for the induction of anoxygenic photosynthesis. Most cyanobacteria are highly sensitive to sulfide toxicity, and brief exposures to low concentrations cause complete and irreversible cessation of CO(2) photoassimilation. Resistance of photosystem II to sulfide toxicity, allowing for oxygenic photosynthesis under sulfide, is found in cyanobacteria exposed to low H(2)S concentrations in various hot springs. When H(2)S levels exceed 200 muM another type of adaptation involving partial induction of anoxygenic photosynthesis, operating in concert with partially inhibited oxygenic photosynthesis, is found in cyanobacterial strains isolated from both hot springs and hypersaline cyanobacterial mats. The fourth type of adaptation to sulfide is found at H(2)S concentrations higher than 1 mM and involves a complete replacement of oxygenic photosynthesis by an effective sulfide-dependent, photosystem II-independent anoxygenic photosynthesis. The ecophysiology of the various sulfide-adapted cyanobacteria may point to their uniqueness within the division of cyanobacteria.

Journal Article↗

Transition from Anoxygenic to Oxygenic Photosynthesis in a Microcoleus chthonoplastes Cyanobacterial Mat.

Benthic cyanobacterial mats with the filamentous Microcoleus chthonoplastes as the dominant phototroph grow in oxic hypersaline environments such as Solar Lake, Sinai. The cyanobacteria are in situ exposed to chemical variations between 200 mumol of sulfide liter at night and 1 atm pO(2) during the day. During experimental H(2)S to O(2) transitions the microbial community was shown to shift from anoxygenic photosynthesis, with H(2)S as the electron donor, to oxygenic photosynthesis. Microcoleus filaments could carry out both types of photosynthesis concurrently. Anoxygenic photosynthesis dominated at high sulfide levels, 500 mumol liter, while the oxygenic reaction became dominant when the sulfide level was reduced below 100 to 300 mumol liter (25 to 75 mumol of H(2)S liter). An increasing inhibition of the oxygenic photosynthesis was observed upon transition to oxic conditions from increasing sulfide concentrations. Oxygen built up within the Microcoleus layer of the mat even under 5 mmol of sulfide liter (500 mumol of H(2)S liter) in the overlying water. The implications of such a localized O(2) production in a highly reducing environment are discussed in relation to the evolution of oxygenic photosynthesis during the Proterozoic era.

Journal Article↗

Testicular seminoma: results of treatment at the Northern Israel Oncology Center.

The survival, and the patterns and mechanisms of failure of 41 patients with pure testicular seminoma treated at the Northern Israel Oncology Center from 1968 to 1983 were analyzed. The actuarial 5-year survival of all patients was 85.4% and of stage I patients, 92.2%. Treatment failures were analyzed. The following conclusions were reached: in order to increase the cure rate, the use of combination chemotherapy as the initial treatment modality in advanced seminoma is recommended. In cases of transscrotal approach, the scrotum should be irradiated. Adjuvant mediastinal irradiation is not needed.

Combined Modality Therapy↗

[Detection of endotoxins in radiopharmaceutical preparations--I. Comparison of rabbit hyperthermia after intravenous or intrathecal administration of reference endotoxin preparations].

The rise of the rabbit internal temperature after endotoxin injection is related to the route of administration. A rise of 1.71 +/- 0.411 degrees C is obtained after i.v. injection of 1 ng/kg Escherichia coli 0111.B.4 endotoxin. An increase of 1.93 +/- 0.236 degrees C is obtained after suboccipital intrathecal injection of 0.1 ng/kg of the same endotoxin; with the intrathecal route, the hyperthermia is induced by E. coli endotoxin after a dose ten times lower than with i.v. injection as shown by statistical analysis.

Animals↗

[Detection of endotoxins in radiopharmaceutical preparations--II. Comparison of the sensitivity of methods using the rabbit and the Limulus amoebocyte lysate for the detection of endotoxins].

The rise of the rabbit internal temperature after i.v. injection of an endotoxin solution is proportional to concentration. Gelation of Limulus amoebocyte, when in presence of an endotoxin solution, is also related to concentration. We compared the sensitivity of these two methods. With our experimental procedure, the rabbit is sensitive to a 0.40 ng/mL solution and the Limulus amoebocyte lysate to a 0.14 ng/mL solution. The rabbit sensitivity increase is related to the per kilogramme injected volume, whereas sensitivity is not related to the volume to check in the case of the lysate.

Animals↗

[Detection of endotoxins in radiopharmaceutical preparations--III. Limulus test assessment using radiopharmaceutical preparations; correlation with the rabbit pyrogen test].

Experiments using 17 radiopharmaceuticals containing known amounts of added endotoxin show that none of them inhibits the pyrogenic reaction of the rabbit. Gelation of the Limulus amoebocyte lysate (LAL) is inhibited by 4 of them: colloidal erbium 169Er citrate, colloidal rhenium 186Re sulfide, colloidal technetium 99mTc (Re) sulfide for liver scintigraphy and the colloidal technetium 99mTc (Re) sulfide for lymphography. This inhibition is cancelled, either by dilution or after neutral pH adjustment. Both controls were performed on 313 batches of various radiopharmaceuticals, 95% of results were identical (93% negative, 2% positive). The remaining 5% correspond to positive LAL tests vs negative rabbit tests on the same batches. No negative LAL test vs positive rabbit test was observed.

Animals↗

Mitomycin, doxorubicin, and vinblastine as second-line chemotherapy in patients with advanced breast cancer.

Thirty-seven patients with disseminated breast cancer refractory to previous therapy were treated with a combination of mitomycin, doxorubicin, and vinblastine (MAV). One complete and eight partial responses were achieved, with an overall response rate of 24.3%. The median duration of response was 5+ months. The MAV regimen had generally moderate but acceptable toxicity. This study indicates that the MAV combination is no better than doxorubicin given as a single agent.

Adult↗

Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma.

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.

Actuarial Analysis↗