Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney

The effect of chloroquine (CHQ) administration on antioxidant enzymes in rat liver and kidney was studied. Male Sprague-Dawley rats were administered 20 mg/kg CHQ once a week for 4 weeks (chronic treatment) or a single dose at 10 or 20 mg/kg (acute treatment). Antioxidant enzyme activities were determined in cytosolic fractions of liver and kidney, whereas reduced glutathione (GSH) and malondialdehyde (MDA) were determined in tissue samples. Results indicate minimal effects of acute CHQ treatment, whereas chronic treatment with CHQ differentially affected antioxidant enzymes in the two organs. Superoxide dismutase activity was increased nearly twofold, while activities of selenium glutathione peroxidase (GPX), catalase, and NAD (P) H: quinone oxidoreductase were decreased in livers of CHQ-treated rats compared to controls. No significant effects of CHQ on glutathione reductase, GSH, and MDA levels were seen in the liver. Fewer effects of CHQ were observed in the kidney where a decrease in GPX activity and an increase in MDA levels was seen. Lowering of antioxidant enzymes activities in the liver by CHQ could render the organ more susceptible to subsequent oxidative stress; while increased MDA production after CHQ treatment in the kidney indicate that the organ is being subjected to oxidative stress. This could have implications for prolonged chloroquine intake.     

In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.     

Interaction between the Drug Information Centre and the Regional Centre for Adverse Drug Reaction Monitoring in northern Sweden

Two Ghanaian women, aged 21 and 29 years, who were involved in road traffic accidents sustaining blunt trauma to the chest and who had delayed diagnosis of their total bronchial rupture and underwent successful surgical repair 18 and 29 months, respectively after injury are reported with a review of the literature. We believe these to be the first reported cases of delayed diagnosis and successful repair of total bronchial rupture in Tropical Africa.     

Antitumor effect of DT-5461, a lipid A derivative, against human tumor xenografts is mediated by intratumoral production of tumor necrosis factor and affected by host immunosuppressive factors in nude mice

PURPOSE OF THE STUDY: The purpose of this report was to study the repercussions of rotator cuff condition on unconstrained shoulder arthroplasty results. METHODS: Between 1986 and 1993, 40 unconstrained shoulder prostheses were performed (24 total and 16 hemiarthroplasties). At the time of the operation, rotator cuff condition was reported to be normal in 15 shoulders, atrophic in 10, scarred in 3, torn in 12. Clinical and radiographical results were analyzed and supplemented with a rotator cuff echography. Postoperative follow-up averaged 42.25 months (12 to 97 months). RESULTS: When the rotator cuff was intact at the time of operation, clinical results were the best at the time of review. Constant score, overall mobility, forward elevation, external rotation with the elbow along the side were better for intact than for atrophic, scarred or torn rotator cuffs (p < 0.01). Ruptures repaired by local tissue transfer or trapezo deltoidal flap substitution (3 cases) gave satisfactory results, whereas two dacron cuff prostheses failed. In the non repaired ruptures (7 cases), arthroplasty resulted in 3/4 fair or poor results. At the time of review, the total incidence of postoperative rotator cuff tears was high (12 cases), functional repercussions were variable. Among the 15 rotator cuff tears observed at the time of the review, the long head of the biceps was present and in place in 9 cases and ruptured in 6 cases. In these latter cases, Constant score (p < 0.01), the forward elevation (p < 0.01), external rotation with elbow along side (p < 0.05) and overall mobility (p < 0.05) were worse; moreover, humeral head superior migration was greater (p < 0.01). DISCUSSION: Our study confirms the superiority of clinical results when the cuff was intact at the time of the operation. The repair of rotator cuff tears seems to be justified. When the rupture has not been repaired, clinical results were fair or poor in 5 cases out of 7, the initial rupture spread to the other tendons in 3 cases out of 7. Secondary ruptures were frequent (12 cases). No predictive factor was identified, but an overlapping of the greater tuberosity appears to be detrimental. Among rotator cuff tears present at the time of review, long head of the biceps rupture jeopardized clinical results and was associated with a proximal migration of the humeral head which was significantly more severe than with an intact non displaced long head of the biceps. CONCLUSION: During unconstrained shoulder prosthesis implantation, it is therefore recommend to systematically repair any associated rotator cuff rupture, in order to avoid any greater tuberosity overlap relative to the prosthetic head and to preserve the long head of the biceps tendon which limits upward migration of the humeral head and improves prosthetic kinetics.     

Ability of pediatric residents to read critically research papers]

PURPOSE: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). RESULTS: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. CONCLUSION: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.     

Long-term observation of subcutaneous tissue reaction to synthetic auditory ossicle (Apaceram) in rats

The present study evaluates histological characteristics of the soft tissue response to long-term implantation of Apaceram discs composed of dense hydroxyapatite in rats. Discs were implanted into the subcutaneous tissue of 76 rats for six to 20 months. Decalcified histological sections stained with haematoxylin and eosin (H & E) and Mallory's azan were examined. Different cell types surrounding implants were counted. The greatest proportion of macrophages was found at six months (13.5 per cent). This proportion gradually decreased to four per cent at 20 months. Small numbers of lymphocytes and foreign body giant cells were observed in every group, but neither neutrophils nor osteogenesis were observed in any specimens. Results of the present study and previous related studies indicate that despite reappearance of a small number of macrophages six months after implantation, Apaceram is useful for reconstructive surgery.     

Insights into multistep phosphorelay from the crystal structure of the C-terminal HPt domain of ArcB

The histidine-containing phosphotransfer (HPt) domain is a novel protein module with an active histidine residue that mediates phosphotransfer reactions in the two-component signaling systems. A multistep phosphorelay involving the HPt domain has been suggested for these signaling pathways. The crystal structure of the HPt domain of the anaerobic sensor kinase ArcB has been determined at 2.06 A resolution. The domain consists of six alpha helices containing a four-helix bundle-folding. The pattern of sequence similarity of the HPt domains of ArcB and components in other signaling systems can be interpreted in light of the three-dimensional structure and supports the conclusion that the HPt domains have a common structural motif both in prokaryotes and eukaryotes.     

Low molecular weight heparins. Implications in anesthesia and resuscitation

Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).