Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver.

Previous studies in our laboratory have demonstrated the effect of Schisandrin B (Sch B),an active ingredient of the fruit of Schisandra chinensis, on enhancing the hepatic glutathione antioxidant system in mice, as evidenced by the hepatoprotection against carbon tetrachloride (CCl4) toxicity. In the present study, the mechanism involved in the hepatoprotection afforded by Sch B treatment was investigated. Treating female Balb/c mice with 1, 3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase (GRD), at a dose of 2 mmol/kg (i.p.) did not abrogate the hepatoprotective action of Sch B in CCl4-treated mice. The result indicates that the increased activity of hepatic GRD is not ascribable to the hepatoprotective action of Sch B. In control mice, the same Sch B treatment regimen caused an enhancement in hepatic mitochondrial glutathione redox status, as indicated by the significant increase and decrease in reduced and oxidized glutathione levels, respectively. While the CCl4 intoxication greatly impaired mitochondrial glutathione redox status, the beneficial effect of Sch B treatment became more evident after CCl4 challenge. Our results strongly suggest that the mechanism of hepatoprotection afforded by Sch B treatment may involve the enhancement of mitochondrial glutathione redox status.

The recovery of some components of the renin angiotensin system in the rat pancreas after chronic exposure to hypoxic condition.

Previous studies have shown that the expression of the major components from a local pancreatic renin-angiotensin system (RAS) was upregulated after chronic exposure to oxygen deprivation (10% oxygen). In the present study, the reversibility of expression for the pancreatic RAS affected by chronic hypoxia was investigated in the pancreas. Rats were first subject to hypoxia for one Month and they were then returned to normoxic conditions for a varying period of time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS components was analyzed with standard curve-quantitative competitive-reverse transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and a specific assay for angiotensin-converting enzyme (ACE) activity. Results from SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1 (AT(1)) receptor mRNA following chronic hypoxia could be completely restored to the control level after the rats were returned to the normoxic condition for 3 weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT(2)) receptor and angiotensinogen was observed after the return to normoxic conditions for 2 and 3 weeks respectively when compared with that of their respective controls. Results from Western blot analysis further confirmed that the expression of AT(1) receptor protein was also reversible after return to normoxic conditions for 4 weeks. In addition, the activation of ACE activity returned to its normal level in a time-dependent manner. These data indicate that the upregulation of a local pancreatic RAS affected by chronic hypoxia could be recoverable. The significance of its reversibility and adaptability following chronic hypoxia may be of physiological relevance to the pancreas.

The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: a comparative study with butylated hydroxytoluene.

A comparison between the effects of schisandrin B (Sch B) and butylated hydroxytoluene (BHT) treatments on hepatic antioxidant status was made to identify the critical antioxidant action of Sch B involved in hepatoprotection in mice. Whereas Sch B treatment (3 mmol/kg/day x 3, p.o.) increased the hepatic mitochondrial-reduced glutathione (GSH) level, BHT treatment at the same dosage regimen decreased it. However, both Sch B and BHT increased, albeit to a different extent, the activity of mitochondrial glutathione reductase. The differential effect of Sch B and BHT treatment on hepatic mitochondrial glutathione status became more apparent after carbon tetrachloride (CCl4) challenge. Pretreatment with Sch B could sustain the hepatic mitochondrial GSH level in CCl4-intoxicated mice and protect against CCl4 hepatotoxicity. BHT pretreatment did not produce any protective effect on CCl4-induced GSH depletion in mitochondrion and hepatocellular damage. Although both Sch B and BHT treatments increased hepatic ascorbic acid (VC) level in control animals, only Sch B pretreatment sustained a high hepatic VC level in CCl4-intoxicated mice. Moreover, Sch B pretreatment prevented the CCl4-induced decrease in the hepatic alpha-tocopherol (VE) level. However, Sch B inhibited NADPH oxidation in mouse liver microsomes incubated with CCl4 in vitro, whereas BHT stimulated this oxidation. The ensemble of results suggests that the ability to sustain the hepatic mitochondrial GSH level and the hepatic VC and VE levels may represent the crucial antioxidant action of Sch B in protection against CCl4 hepatotoxicity. The possible inhibition of CCl4 metabolism by Sch B may also contribute to its hepatoprotective action.

Methylenedioxy group as determinant of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-intoxicated mice.

As a preliminary approach to exploring whether the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrins plays an important role in hepatic mitochondrial-reduced glutathione (GSH) stimulatory activity, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and hepatic mitochondrial GSH status in mice. Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen produced almost complete protection. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important structural determinant in the stimulation of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.

Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver.

Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of D-galactosamine sensitized mice, as evidenced by the increase in the extent of DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with hepatocellular damage as assessed by plasma alanine aminotransferase activity. Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis in mice. The hepatoprotection was accompanied by a parallel reduction in the extent of hepatocellular damage. The same Sch B pretreatment regimens increased hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic apoptosis remains to be elucidated.

Association of free radicals and the tissue renin-angiotensin system: prospective effects of Rhodiola, a genus of Chinese herb, on hypoxia-induced pancreatic injury.

The renin-angiotensin system has long been recognized as crucial factor in the regulation of the systemic blood pressure and renal electrolyte homeostasis. Numerous studies have demonstrated the presence of a local renin-angiotensin system in a variety of organs. A recent study of the pancreatic renin-angiotensin system showed that chronic hypoxia significantly increased the mRNA expression for angiotensinogen II receptor subtypes AT1b and AT2. The activation of the renin-angiotensin system may play an important role in cellular pathophysiological processes. Angiotensin II enhances the formation of reactive oxygen species via the activation of xanthine oxidase or NAD(P)H oxidase. The reactive oxygen species can cause oxidative damage in the pancreas and other tissues either directly or indirectly via the formation of other radicals such as reactive nitrogen species. Rhodiola therapy may protect hypoxia-induced pancreatic injury in two ways. It prevents hypoxia-induced biological changes by increasing intracellular oxygen diffusion and efficiency of oxygen utilization. Alternatively, it reduces hypoxia-induced oxidative damage by its antioxidant activities. Additional experimental data are required to fully elucidate the mode of action of this herbal drug.

Short-stay in-patient rehabilitation of elderly patients with chronic obstructive pulmonary disease: prospective study.

OBJECTIVES: To evaluate the effectiveness of a short-stay in-patient rehabilitation programme. DESIGN: Prospective case-control cohort study. SETTING: Regional medical centre, Hong Kong. PATIENTS: One hundred and thirty symptomatic elderly patients with chronic obstructive pulmonary disease who had been treated for an acute respiratory illness in 1998. They were divided into two groups: the conventional treatment group, which received no rehabilitation (n=65), and the rehabilitation group (n=65). INTERVENTION: A short-stay in-patient rehabilitation programme was implemented, which included assessment, patient and caregiver education, an exercise regimen, physiotherapy, occupational therapy, and case conference. MAIN OUTCOME MEASURES: Length of stay, hospital re-admission rate, and admission-free interval. RESULTS: The mean length of stay in the rehabilitation ward was 6.2 days. The rate of hospital re-admission was significantly higher in the conventional treatment group than in the rehabilitation group, both within 28 days of discharge home (relative risk=3.33; 95% confidence interval, 2.32-4.56; P=0.019) and at 100 days after discharge (relative risk=2.47; 95% confidence interval, 1.78-3.48; P<0.001). The admission-free interval was significantly longer in the rehabilitation group than in the conventional treatment group (1.13 years vs 0.86 years; P<0.001). CONCLUSION: A short-stay in-patient rehabilitation programme is effective in reducing hospital re-admission rates. This type of rehabilitation service may be important for elderly patients, as well as for patients with more advanced disease and more functional deficits than others.

Unimuscular neuromuscular insult of the leg in partial anterior compartment syndrome in a patient with combined fractures.

A complicated case of ipsilateral fractures of the left femur and tibia after a road traffic accident is reported. The patient presented with numbness of the first web of his left foot and contracture of the extensor hallucis longus muscle, with fixed length deformity after intramedullary nailing of the femur and tibia. The extensor digitorum longus and tibialis anterior muscles were spared. Tinel's sign could be elicited at the mid-portion of the anterior compartment of the injured leg. This indicated that the distal half of the anterior tibial nerve (deep peroneal nerve), together with the extensor hallucis muscle of the anterior compartment of the leg, had been damaged. The subsequent management of this patient is described.

Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats.

BACKGROUND: Nitric oxide (NO) is implicated in the pathogenesis of irritable bowel syndrome (IBS) but the underlying mechanism is unclear. Thus, the aim of the present study is to examine the role of NO synthase (NOS) expression in the distal colon of neonatal maternal separation (NMS) model rats employed in IBS studies. METHODS: Male neonates of Sprague-Dawley rats were randomly assigned into NMS and normal control (N) groups. Rats of NMS group were subjected to 3 h daily maternal separation on postnatal day 2-21. Rats were administrated non-selective NOS inhibitor l-NAME (100 mg kg(-1) ), selective neuronal NOS (nNOS) inhibitor 7-NINA (10mgkg(-1) ), selective inducible NOS (iNOS) inhibitor, endothelial NOS (eNOS) inhibitor (10mgkg(-1) ) or Vehicle (Veh; distilled water) intraperitoneally 1h prior to the experiment for the test and control groups, respectively. KEY RESULTS: The amount of NO was significantly higher in the NMS Veh rats compared with unseparated N rats. Western-blotting and real-time quantitative PCR studies showed that protein and mRNA expression of nNOS were higher in the NMS group than that in the N rats; whereas no significant change in iNOS and eNOS was found in either groups. Neonatal maternal separation Veh rats showed low pain threshold and increased electromyogram (EMG) activity in response to colonic distension stimuli. l-NAME and 7-Nitroindazole monosodium salt (7-NINA) increased pain threshold pressure and attenuated EMG activity in the NMS rats. In addition, l-NAME and 7-NINA substantially reduced oxidative marker malondialdehyde level in NMS rats. CONCLUSIONS & INFERENCES: Neonatal maternal separation increased the NO generation by nNOS upregulation that interact with reactive oxygen species contributing to the visceral hypersensitivity in IBS.

Accessory radial collateral vascular bone graft for the management of nonunion of humeral shaft fracture after intramedullary nailing.

SUMMARY: An easy pedicle vascular bone graft technique for the management of nonunion of humeral shaft fracture is described. The distal and lateral part of the humerus, including the lateral epicondyle, is transferred to the nonunion site of the humerus. This vascular bone graft is based on the accessory radial collateral artery. It promotes healing of the nonunion.

Trans-triquetral dorsal perilunate fracture dislocation.

A rare case of trans-triquetral dorsal perilunate dislocation is described. It differs from the Mayfield and Johnson theory of progressive perilunar instability in greater arc injuries which states that the injury passes from the radial to the ulnar carpal bones and soft tissues in stages. This injury supports the concept of a reverse greater arc injury from ulnar to radial being possible with the radial carpal bones being spared in some cases.

The crisscross injury mechanism in forearm injuries.

INTRODUCTION: A new mechanism of injury of the forearm bones, crisscross injury, is described. It is more common than the Essex-Lopresti fracture dislocation. The old concept of isolated injury of one side of the radioulnar joint may be challenged. It often occurs in Mason type II fracture dislocation of the radial head or dislocation of radioulnar joints. MATERIALS AND METHODS: The first part was a cadaveric study of the crisscross injury of forearms. The second part was a clinical study of the crisscross injury in some cases of Mason type II fracture radial head and double dislocation of the radioulnar joint. RESULTS: The cadaveric study confirmed a stable crisscross fracture dislocation injury with intact interosseous membrane. The clinical study echoed the presence of this injury by imaging techniques. CONCLUSION: The crisscross injury mechanism explains the mirror pathogenesis of the traumatic fracture dislocation of the distal and proximal radioulnar joints with intact shaft of the radius and ulna. Co-existing subluxation or dislocation of the other radioulnar articulation must not be overlooked in cases of fracture dislocation of one radioulnar joint. Two types of crisscross injury of forearm bones are proposed.

Depression in institutionalised older people with impaired vision.

OBJECTIVES: For depression in institutionalised elders with visual impairment, there is a lack of information in the literature. A panel study was performed: (1) to determine the prevalence of depressive symptoms, and (2) to investigate the risk factors of depression. METHOD: Residents of a nursing home for the aged blind were recruited. Measurements included: Geriatric Depression Scale (GDS), Snellen Eye Chart, age, duration of institutionalisation, duration of impaired vision, and functional ability. RESULTS AND CONCLUSIONS: The proportion of participants who scored GDS> or =6/15 was 45.2%. The rate of depression among visually impaired nursing home residents is higher compared to other populations reported. The depressed participants had significantly shorter duration of institutionalisation (3.4 years vs 7.1 years, rank-sum, p=0.007) and lower functional ability (Barthel Index 60.7/100 vs 85.6/100, rank-sum, p=0.002) as compared to the non-depressed. No significant difference was found in age and length of impaired vision. A logistic regression model predicting depressive symptoms found that the duration of institutionalisation (odds ratio 0.75; 95% confidence interval 0.59-0.94), and functional ability (odds ratio 0.96; 95% confidence interval 0.92-0.99), were independently and inversely associated with depressive mood after controlling for age and duration of blindness. The effects of blindness and living in a long-term care institution were identified. Recommendations on screening and management of depression were provided.

Chronic erosion injury of a digit by a ring: epidemiology, staging, treatment and prognosis.

A 71-year-old man who presented with chronic erosion of a digit by an ornamental ring is reported. The literature is reviewed; and the epidemiology, risk factors, staging, treatment and outcome are discussed.

Structure-activity relationship of schisandrins in enhancing liver mitochondrial glutathione status in CCl4-poisoned mice.

AIM: To explore whether the methylenedioxy group and cyclooctadiene ring of the dibenzocyclooctadiene skeleton of schisandrins (Sch) play a role in the liver mitochondrial glutathione status enhancing activity. METHOD: The effects of three dibenzocyclooctadiene derivatives, Sch A, Sch B, Sch C, and a synthetic intermediate of Sch C, (dimethyl biphenyl dicarboxylate, DBD) on carbon tetrachloride (CCl4)-hepatotoxicity and liver mitochondrial glutathione status were examined in mice. RESULTS: Pretreating mice with intragastric Sch B, Sch C, or DBD 1.mmol.kg-1.d-1 for 3 d protected against CCl4-hepatotoxicity. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with increases in liver mitochondrial reduced glutathione (mtGSH) level and glutathione reductase (mtGRD) activity, an indication of enhanced mitochondrial glutathione status. In contrast, the hepatoprotective action of DBD was not accompanied by any detectable changes in mtGSH level and mtGRD activity. CONCLUSION: Both the methylenedioxy group and the cyclooctadiene ring of the dibenzocyclooctadiene molecule are important structural determinants in the enhancement of liver mitochondrial glutathione status.

Differential effect of schisandrin B and dimethyl diphenyl bicarboxylate (DDB) on hepatic mitochondrial glutathione redox status in carbon tetrachloride intoxicated mice.

The effects of schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, and dimethyl diphenyl bicarboxylate (DDB), a synthetic intermediate of schisandrin C (also a dibenzocyclooctadiene derivative), on hepatic mitochondrial glutathione redox status in control and carbon tetrachloride (CCl4)-intoxicated mice were examined. Treating mice with Sch B or DDB at a daily oral dose of 1 mmol/kg for 3 d did not produce any significant alterations in plasma alanine aminotransferase (ALT) and sorbital dehydrogenase (SDH) activities. CCl4 treatment caused drastic increases in both plasma ALT and SDH activities in mice. Pretreating mice with Sch B or DDB at the same dosage regimen significantly suppressed the CCl4-induced increase in plasma ALT activity, with the inhibitory effect of Sch B being much more potent. Sch B, but not DDB, pretreatment could also decrease the plasma SDH activity in CCl4-intoxicated mice. The lowering of plasma SDH activity, indicative of hepatoprotection against CCl4 toxicity, by Sch B pretreatment was associated with an enhancement in hepatic mitochondrial glutathione redox status as well as an increase in mitochondrial glutathione reductase (mtGRD) activity in both non-CCl4 and CCl4-treated mice. DDB pretreatment, though enhancing both hepatic mitochondrial glutathione redox status and mtGRD activity in control animals, did not produce any beneficial effect in CCl4-treated mice. The difference in hepatoprotective action against CCl4 toxicity between Sch B and DDB may therefore be related to their ability to maintain hepatic mitochondrial glutathione redox status under oxidative stress condition.

Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity.

Pretreating mice with schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 1 mmol/kg for 3 days protected against menadione-induced hepatic oxidative damage in mice, as evidenced by decreases in plasma alanine aminotransferase activity (78%) and hepatic malondialdehyde level (70%), when compared with the menadione intoxicated control. In order to define the biochemical mechanism involved in the hepatoprotection afforded by Sch B pretreatment, we examined the activity of DT-diaphorase (DTD) in hepatocytes isolated from Sch B pretreated rats. Hepatocytes isolated from Sch B pretreated (a daily dose of 1 mmol/kg for 3 days) rats showed a significant increase (25%) in DTD activity. The increase in DTD activity was associated with the enhanced rate of menadione elimination in the hepatocyte culture. The ensemble of results suggests that the ability of Sch B pretreatment to enhance hepatocellular DTD activity may at least in part be attributed to the protection against menadione hepatotoxicity.

Prooxidant and antioxidant effects of Trolox on ferric ion-induced oxidation of erythrocyte membrane lipids.

The prooxidant and antioxidant actions of Trolox were examined in an in vitro system measuring ferric ion-induced oxidation of erythrocyte membrane lipids. Trolox was found to produce a concentration-dependent biphasic effect on the ferric ion-stimulated lipid peroxidation, with the mode of action being similar to those produced by reducing-agent antioxidants, such as ascorbic acid and reduced glutathione, and iron chelator, such as desferrioxamine. Phytic acid, a potent iron chelator, could suppress the prooxidant actions of Trolox and desferrioxamine, but not those of ascorbic acid and reduced glutathione. The ability of Trolox to stimulate ferric ion-catalyzed ascorbate oxidation, as similar to the action produced by ethylenediaminetetraacetic acid, indicates the presence of iron-chelating activity. The ensemble of results suggests the possible involvement of iron chelation in the prooxidant action of Trolox in ferric ion-stimulated lipid peroxidation reactions.

Trephine bone grafting technique for the treatment of scaphoid nonunion.

A simple, minimally invasive trephine bone grafting technique for the treatment of scaphoid fracture nonunions is described. The method has a short surgical time, good results, and minimal donor site morbidity.