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Biomedical subjects

J Jacob

Publications and source records attributed to J Jacob.

At least 163 records · Page 9Linked to original sources

Metabolism of benz(a)anthracene catalyzed by liver microsomes of untreated and nicotine-pretreated rats.

The purpose of the present investigation was to determine whether nicotine causes an induction or alteration of rat liver microsomal monooxygenases (cytochromes P-450) involved in the metabolism and activation of polycyclic aromatic hydrocarbons. After 2, 4, and 10 days of continuous nicotine treatment (16.8 mg/day) neither an increase of benz(a)anthracene metabolism nor an alteration of the metabolite pattern could be observed in comparison to controls. Moreover, there was no significant change of cytochrome P-450 content or benzo(a)pyrene hydroxylation rates. In further control experiments the inducibility of the rats was tested by pretreatment with benzo(k)fluoranthene. As expected, this treatment resulted in a high increase of metabolism and the formation of the ultimate carcinogen as well as other metabolites of benz(a)anthracene due to the induction corresponding to isocytochrome P-450. For nicotine it can be concluded that this alkaloid cannot cause qualitative or quantitative changes of normal rat liver cytochromes P-450.

Animals↗

Differences in serum glucose determinations in infants with umbilical artery catheters.

Differences in serum glucose values obtained from different extremities in newborns with umbilical artery catheters (UAC) through which a dextrose solution was administered were studied. Control infants (n = 20) had no difference in simultaneous capillary glucose values obtained from both lower extremities. Infants with a low UAC had a significant difference between two (both lower extremities) or three (both lower and one upper extremity) simultaneous capillary glucose values. Infants with a high UAC did not. In the low UAC group, the serum glucose value was highest in the lower extremity through which the UAC entered the aorta and lowest in the upper extremity. The elevation in glucose value was related to the glucose infusion rate corrected for infant size (mg/kg/min). Clinicians caring for infants with low UACs should be aware of this potential error in order to prevent erroneous decision-making.

Blood Flow Velocity↗

Antagonists of mouse paw oedema induced by Habu snake (Trimeresurus flavoviridis) venom. Inhibitions by various antagonists administered alone or in combinations.

When injected into the sole of the hind paw of mice, Habu snake (Trimeresurus flavoviridis) venom produced a prolonged oedema (72 hours). When administered alone, most of the studied drugs (mepyramine, methysergide, cyproheptadine, indomethacin, aspirin, dexamethasone and aprotinin) inhibited this oedema only partially and transiently (less than 7 hours). Some drugs however (EDTA, Biogel P4, zymosan and celluloses) were able to abolish it progressively. Combinations of some of these drugs resulted in various synergisms; in particular important and prolonged inhibitions were observed with aprotinin-dexamethasone, one of these drugs and EDTA, and especially EDTA-zymosan, which abolished totally the oedema from 2 hours after the injection of the venom to its end (72 hours). Antagonisms between components of combinations were also observed. The mechanisms of these synergisms and antagonisms are discussed. In particular, it is suggested that the blockade of the two pathways "classical" and "alternative", of the complement by EDTA and zymosan respectively might account for their important and early synergism. Antagonisms also helped in indicating some mechanisms of action.

Animals↗

Contribution of polycyclic aromatic hydrocarbons and nitro-derivatives to the carcinogenic impact of diesel engine exhaust condensate evaluated by implantation into the lungs of rats.

Diesel exhaust condensate was separated by a liquid-liquid distribution into a hydrophilic (I; about 25% by weight of the total condensate) and a hydrophobic part (II; about 75%-wt.). To evaluate the carcinogenicity, the proportionately dosed fractions have been implanted into the lungs of Osborne Mendel rats and compared with several doses of benzo[a]pyrene and the vehicle, a mixture of trioctanoin plus beeswax. Only the hydrophobic part which contained polycyclic aromatic compounds (PAC) resulted in 5 malignant tumors in a group of 35 animals. In addition, the hydrophobic part was separated by column chromatography on Sephadex LH 20 and subsequently on silica gel into several fractions, such as non-aromatic compounds plus PAC with 2 and 3 rings (IIa; 72%-wt of the total condensate), polycyclic aromatic compounds (PAH) with 4 and more rings (IIb; 0.8%-wt), polar PAC (IIc; 1.1%-wt) and nitro-PAH (IId; 0.7%-wt). PAH consisting of 4 and more rings (IIb) were found to be the most potent subfraction and provoked when proportionately dosed 6 carcinomas in a group of 35 rats. Only a low contribution to the carcinogenicity was observed by the subfraction of nitro-PAH (IId) which produced 1 carcinoma/35 rats. The polar PAC (IIc) and the fraction of non-aromatics plus PAC with 2 and 3 rings (IIa), although the main subfraction (72%-wt of the total condensate) did not provoke any tumors. The reconstitution of all hydrophobic subfractions (IIa-d) resulted in the same carcinogenic potency as the unfractionated hydrophobics (II), provoking 7 carcinoma in 35 rats. It may be concluded from these findings that most of the carcinogenicity of diesel exhaust originates from the PAH consisting of 4 or more rings.

Animals↗

[Demonstration of an NAD-dependent 6-phosphogluconate dehydrogenase in Pseudomonas syringae pv. phaseolicola].

Crude extracts from cells of Pseudomonas syringae pv. phaseolicola, a fluorescent pseudomonad, when grown on glucose contain a NAD-linked 6-phosphogluconate dehydrogenase. The reaction of the enzyme, which produces 14CO2 from 1-14C-6-phosphogluconate, is not inhibited by NaF, a potent inhibitor of the Enter-Doudoroff (ED) pathway enzyme 6-phosphogluconate dehydratase. In the presence of phosphate or arsenate ions the NAD-linked glyceraldehyde-3-phosphate dehydrogenase reacts with glyceraldehyde-3-phosphate which, in the ED pathway, is produced from 6-phosphogluconate and overlaps the 6-phosphogluconate dehydrogenase reaction. Only a small proportion of glucose is metabolized via the 6-phosphogluconate dehydrogenase/oxidative pentose phosphate pathway.

Kinetics↗

Combination chemotherapy of disseminated Kaposi's sarcoma in patients with the acquired immune deficiency syndrome.

Two clinical trials were conducted to assess the efficacy and safety of a combination chemotherapy regimen for the treatment of Kaposi's sarcoma in patients with the acquired immune deficiency syndrome (AIDS). Eighteen consecutive patients with disseminated Kaposi's sarcoma were treated with a six-drug regimen of doxorubicin (Adriamycin), vinblastine, bleomycin/actinomycin D, vincristine, dacarbazine (ABV/ADV). A brief partial or complete response was achieved in 13 patients. Most patients died of opportunistic infections. Eighteen consecutive patients with disseminated Kaposi's sarcoma were then randomly assigned to therapy with either recombinant alpha interferon or ABV/ADV. The treatment responses in these two groups were comparable to results of earlier trials, and the incidence of opportunistic infections during therapy did not differ between the two treatment arms. It is concluded that chemotherapy is effective and safe for use in palliative management of Kaposi's sarcoma in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Monooxygenase induction by various xenobiotics and its influence on rat liver microsomal metabolism of chrysene in comparison to benz[a]anthracene.

The potencies of various xenobiotics for induction of monooxygenases and their influence on the rat liver microsomal metabolite profile of the environmentally relevant weak carcinogen, chrysene, was determined. Among the widely distributed chemicals, polychlorinated biphenyls (PCB) and preferentially 3,3',4,4'-tetrachlorobiphenyl as well as PAHs and their heterocyclic analogues such as benzo[a]pyrene, benzo[b]- and -[j]fluoranthene, indeno[1,2,3-cd]pyrene, dibenz[a,h]acridine, benzo[b]naphtho-[2,1-d]thiophene, and 5,6-benzoflavone were found to be potent inducers stimulating the formation of the proximate, and some of them also the ultimate carcinogen of chrysene. Lindane, carbaryl, DDT, and pentachlorophenol were found to be inefficient or weak inducers. With the exception of phenobarbital no inducers were found among the pharmaceuticals investigated. Sex-dependent metabolism was found for Wistar-rats. No 1,2-oxidation was observed in females, and turnover rates were lower than in males. These findings confirm the results previously obtained with benz[a]anthracene as substrate. The inducing potencies of various compounds tested were similar for both of these substrates. It is interesting to note that in most cases the same effective xenobiotic induces the bay-region diolepoxide in both, chrysene and benz[a]anthracene.

Animals↗

Comparison of chrysene metabolism in epithelial human bronchial and Syrian hamster lung cells.

Chrysene is metabolized to 1-, 2-, 3-, and 4-hydroxychrysene and trans-1,2- as well as trans-3,4-dihydroxydihydrochrysene in human and Syrian hamster epithelial lung cells as indicated by GC/MS analysis, whereas K-region oxidation is at most a very minor pathway. Cells of a permanent clonal line of fetal hamster lung metabolized 97% of the chrysene whereas fetal human bronchial epithelial cells converted 24% of the substrate within 8 days incubation. In human cells oxidation at the 3,4-position predominates, whereas oxidation at the 1,2-position is the major pathway in hamster cells. Indication for a bay-region oxidation of chrysene in hamster cells has been obtained.

Animals↗

Distal interphalangeal joint involvement in rheumatoid arthritis.

Sixty-two patients with seropositive rheumatoid arthritis (RA) were evaluated radiographically for distal interphalangeal (DIP) joint involvement and were compared with 50 age- and sex-matched control subjects. The frequency of DIP erosions was 37% in the patients versus 14% in the controls; these erosions were mild and were not related to disease duration. Erosions elsewhere in the hand and wrist were of all degrees of severity and were related in part to disease duration. Osteophytes occurred frequently in both the RA group (71%) and the control group (60%). However, joint space narrowing occurred more frequently in RA patients (77%) than in the controls (46%) (P less than 0.009). The findings from this study suggest that in RA patients, DIP erosions occur frequently, do not occur in isolation, and are not simply a marker for severe global erosive disease in the hand and wrist. The high frequency of osteophytosis and joint space narrowing in both groups probably represents the overlap of osteoarthritis and RA that occurs in many patients.

Arthritis, Rheumatoid↗

The predominant role of S-oxidation in rat liver metabolism of thiaarenes.

Thiaarenes are metabolized by liver microsomes of untreated rats predominantly to sulfones and sulfoxides. After pretreatment of rats with monooxygenase inducers, ring oxidation of thiaarenes is also observed. In case of benzo[b]naphtho[2,3-d]thiophene the formation of a p-quinone takes place. Rat liver microsomal metabolism of the thiaarenes tested as substrates did not resemble that of the polycyclic aromatic hydrocarbon (PAH) isosters at all.

Animals↗

Tetany induced by hypokalemia in the absence of alkalosis.

A 36-year-old patient developed tetany manifested only by a positive Trousseau's sign and with a negative Chvostek's sign 8 weeks after gastric bypass surgery for obesity. The usual causes of tetany (hypocalcemia, hypomagnesemia and alkalosis) were absent. The only possible etiology found was hypokalemia. Previous cases of hypokalemia induced tetany reported were always accompanied by alkalosis. Its absence in our patient makes this case unique and determines that hypokalemia per se in the absence of alkalosis may be a cause of tetany. It is suggested that the Trousseau's sign should be investigated in patients with severe potassium deficiency.

Adult↗

Transcutaneous carbon dioxide monitoring during neonatal transport.

We studied the value of transcutaneous carbon dioxide (PtcCO2) monitoring during neonatal transport. Thirty-two neonates with respiratory distress were alternately enrolled in an experimental group (results of PtcO2 and PtcCO2 available for clinical management) and a control group (results of only PtcO2 available). Although differences were not significant, infants in the experimental group had more changes in the intermittent mandatory ventilation (IMV) settings during transport, and more such infants arrived at the receiving hospital with acceptable pH and PCO2 values. On arrival at the receiving hospital, two patients in the control group had acidosis and hypercarbia and were placed on IMV immediately on arrival. No such patients were encountered in the experimental group. For patients needing IMV during transport, the percentage of study time spent with PtcCO2 measurements in the normal range (35 to 45 torr) was greater for the experimental group (p less than .02). Continuous PtcCO2 monitoring during transport offers the opportunity to further decrease the risks of transporting a critically ill neonate.

Blood Gas Analysis↗