Attenuation of contraction-induced skeletal muscle injury by bromelain.

The proteolytic enzyme, bromelain, reportedly has therapeutic effects in the treatment of inflammation and soft tissue injuries. We tested the hypothesis that bromelain attenuates skeletal muscle injury induced by lengthening contractions. The left extensor digitorum longus (EDL) muscle of anesthetized hamsters was injured using a motorized foot pedal which repeatedly flexed/extended the foot through a range of 125 degrees. The EDL muscle was electrically stimulated for 400 ms during plantarflexion. Animals were assigned randomly to either a 0-d group (evaluated 3-h post-injury) or to untreated (UT) or bromelain-treated (T) groups, evaluated 3, 7, or 14 d post-injury. Following injury, T received 5 mg.kg-1 b.w. of bromelain, twice daily. Maximum isometric tetanic force (Po) was measured in vitro, then muscles were fixed, sectioned, and examined for evidence of fiber damage. The Po of injured muscles from T were higher than Po of injured muscles from UT at 3 (18.7 +/- 0.4 vs 16.5 +/- N.cm-2 and 14 d (20.5 +/- 0.6 vs 18.2 +/- 0.6 N.cm-2) (P less than 0.05), but not 7 d (19.5 +/-0.7 vs 17.7 +/- 0.8 N.cm-2). The Po of UT injured muscles were significantly lower than Po of contralateral control muscles at all time periods. Po of injured muscles from T were lower than Po from control muscles at 3 and 7 d (P less than 0.05), but not 14 d. The number of intact fibers of 3-d UT injured muscles was lower than the number of intact fibers in control muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Algorithm for diagnosis and prevention of postoperative deep vein thrombosis

An algorithm is described in this paper for diagnosis and prevention of postoperative deep venous thrombosis. It is presented in the form of a network graph and is based on an evaluation of the relative risk of pulmonary embolism of 17.785 patients. Age above 60 years, malignant disease, and more than four days of postoperative immobilisation were found to be the greatest risk factors for lethal embolism of the pulmonary artery. Examination of the venous flow bed by non-invasive methods has proved to be indicated for any patient who has not resumed spontaneous movement on the fourth postoperative day. Diagnostic coverage has so far been achieved for 75 per cent of all patients still immobilised four days after surgery. Peroral or rectal administration of aspirin (1.5 g:24 h-1) is recommended for its good therapeutic effectiveness to reduce complications and for economic reasons.     

The synergistic effect of hyperthermia and chemotherapy on murine transitional cell carcinoma

The in vivo effect of hyperthermia and chemotherapy was studied in a murine transitional cell carcinoma model. Localized hyperthermia (43.5C) of 60 and 90 minutes duration was combined with systemic doxorubicin hydrochloride, cis-platinum, cyclophosphamide or mitomycin to treat tumors implanted into the hind legs of C3H mice. The data were compared to the results obtained from the application of hyperthermia or chemotherapy alone as well as to the natural growth rate of untreated tumors. Untreated tumors grew with an exponential rate and had a doubling time of 4 +/- 1.5 days. Animals bearing such tumors survived for 25 +/- 7 days. When treated with hyperthermia alone, there was no significant reduction in the growth rate and no improvement was noted in the survival time. Treatment with doxorubicin hydrochloride, cyclophosphamide or mitomycin administered alone was likewise not effective. Cis-platinum alone was able to induce a minimal decrease in the growth rate. When the administration of chemotherapy was accompanied by hyperthermia, significant synergistic effect was noted for doxorubicin hydrochloride, cis-platinum and cyclophosphamide (p less than .01); only the mitomycin and hyperthermia combination failed to improve survival and decrease the growth rate. The duration of the hyperthermia exposure influenced the degree of tumor response. Hyperthermia of 90 minutes duration resulted in consistently greater decrease in tumor growth rate with doxorubicin hydrochloride, cis-platinum or cyclophosphamide than 60 minutes of hyperthermia combined with the same agents. These results indicate that local hyperthermia combined with doxorubicin hydrochloride, cis-platinum or cyclophosphamide can induce tumor regression, increase tumor doubling time and improve the survival of the tumor-bearing animal. Only the hyperthermia-mitomycin combination did not result in significant improvement from the baseline values. Thus, hyperthermia combined with selected chemotherapeutic agents can have an adjuvant effect in the treatment of established, implanted mouse bladder tumors.     

Improvement of iron removal from the reticuloendothelial system by liposome encapsulation of N,N'-bis[2-hydroxybenzyl]-ethylenediamine-N,N'-diacetic acid (HBED). Comparison with desferrioxamine

An iron chelator of low water solubility, HBED, has been encapsulated in the lipid bilayers of unilamellar and multilamellar liposomes. The effectiveness of liposome-encapsulated HBED for removing excess iron burden from the RE system of the mouse liver (i.e., Kupffer cells) has been compared to that of the most commonly used iron chelator, DF, a water-soluble drug. We report the following: (1) At a single dose of 25 mg/kg, HBED in liposomes is more effective in removing excess iron than free nonencapsulated HBED. (2) HBED is a more potent iron chelator than DF; after a single dose of 25 mg/kg, about 25% of the originally injected iron is excreted within 7 days from mice given HBED either in small unilamellar or in large multilamellar liposomes, whereas about 18% is excreted from mice given the same dose of liposome-encapsulated DF. (3) Although the iron burden is introduced into the Kupffer cells, liposome-encapsulated HBED promotes iron excretion mainly via the bile and feces, whereas liposome-encapsulated DF promotes iron excretion through the kidney. (4) Cell fractionation studies show that encapsulation of HBED in the lipid bilayers of liposomes does not alter the uptake pattern of liposomes by the Kupffer and parenchymal cells of the liver; in other words, Kupffer cells are more effective in taking up large-sized multilamellar liposomes while parenchymal cells take up small-sized unilamellar liposomes more effectively. (5) Electron microscopic studies demonstrate that the liver biliary canaliculi are enlarged and filled with vesicular materials in mice given liposome-encapsulated HBED and that this condition does not occur in control mice or mice given liposome-encapsulated DF. Our results have thus demonstrated that liposomes could be very useful as injection vehicles for metal chelators that are not readily soluble in water. HBED is also demonstrated to be far superior to DF, the iron chelator of choice for therapy of transfusional iron overload.     

Targets of emerging therapies for viral hepatitis B and C

Viral hepatitis B and C, structurally two completely different viruses, commonly infect human hepatocytes and cause similar clinical manifestations. Since their discovery, IFN has been a pillar in the treatment. However, because of the different natures of the viruses, therapeutic approaches diverge and new treatment targets are tailored specifically for each virus. Herein, the authors analyse therapeutic approaches for hepatitis B virus (HBV) and hepatitis C virus (HCV) and focus on emerging concepts that are under clinical evaluation. In particular, promising viral inhibitors for HBV and HCV are reviewed and the current status of research for gene therapy for HCV is described. Immune therapy is a fast-moving field with fascinating results which include therapeutic vaccines and toll-like receptor agonists that could improve tomorrow's treatment approaches.     

Xanthogranulomatous pyelonephritis in children.

Xanthogranulomatous pyelonephritis in children, contrary to adult onset, rarely is associated with non-function or calcification. The lesion is predominantly on the left side in children. There appears to be a normal humoral but temporarily impaired cellular immune response in addition to sustained depression of polymorphonuclear chemotaxis. The etiology of this is uncertain but may be attributed partially to hyperosmolarity of serum and urine, and to leukocyte specific antinuclear antibodies. The presence of leukocyte specific antinuclear antibody or cold agglutining may interfere with normal phagocyte chemotaxis requiring tissue macrophages to produce a xanthogranulomatous reaction to bacterial invasion.     

Distribution of retinoic acid-binding proteins in normal and neoplastic mammary tissues

Cellular retinoic acid-binding proteins were detected in chemically induced mammary tumors using sucrose density gradient analysis. Unlabeled retinoic acid did not displace nonspecific binding in the 5S region but was, however, a competitive inhibitor for the specifically binding 2S component. Mammary gland cytosol fractions from both 1-methyl-1-nitrosourea-treated and untreated as well as from lactating rats contained low levels of retinoic acid-binding proteins. 1-Methyl-1-nitrosourea treatment did not result in the increased number of binding sites. Thus, the increase in the levels of binding proteins in tumors most probably occurred during tumor development and probably was not a result of the carcinogen per se. Retinoids which have been shown to be effective in the chemoprevention of mammary carcinogenesis only partially competed for the binding sites, indicating that they may be metabolized prior to their action as an active chemopreventive agent.     

Aberrant renal arteries

A case is reported of a patient with aberrant right renal artery arising at the level of the eleventh thoracic segment associated with renal artery aneurysm and systemic hypertension. Knowledge of the existence of aberrant renal arteries is important because they may be inadvertently damaged during renal surgery and their presence must be considered in evaluating a donor kidney for possible renal transplantation.