Effects Of Different Regimens Research Articles

Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression.

Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear. This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic. Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan). We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.We analysed the results of studies comparing six different intravenous anaesthetics.Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.No difference was noted in the reduction of depression scores observed in participants treated with propofol compared with methohexital (low-quality evidence). These four studies were not designed to detect differences in depression scores.The duration of electroencephalograph (EEG) and of motor seizures was shorter in the propofol group compared with the methohexital group (low-quality evidence). No difference was seen in EEG seizure duration when propofol was compared with thiopental (low-quality evidence).Time to recovery (following commands) was longer among participants after anaesthesia with thiopental compared with propofol (low-quality evidence).For the remaining comparisons of anaesthetics, only single studies or insufficient data were available. Adverse events were inadequately reported in eligible trials, and none of the included trials reported anaesthesia-related mortality. Most of the included studies were at high risk of bias, and the quality of evidence was generally low. The studies were not designed to detect clinically relevant differences in depression scores. Anaesthetic agents should be chosen on the basis of adverse effect profile, emergence and how these medications affect seizure duration. If it is difficult to elicit an adequately long seizure, methohexital may be superior to propofol (low-quality evidence). If a patient is slow to recover from anaesthesia, propofol may allow a faster time to follow commands than thiopental (low-quality evidence). A factor of clinical concern that was not addressed by any study was adrenal suppression from etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet been determined.Larger well-designed randomized studies are needed to determine which intravenous anaesthetic medication leads to the greatest improvement in depression scores with minimal adverse effects.

Weight change trajectory in women with breast cancer receiving chemotherapy and the effect of different regimens

To investigate the trajectory of weight change in Taiwanese women with breast cancer after starting chemotherapy and the impact of chemotherapy regimens on weight change while controlling for age, menopausal status, body mass index, lymph node involvement and changes in habits of dietary fat intake and exercise. Weight gain after adjuvant chemotherapy in women with breast cancer has negative impact on health outcomes. Longitudinal, clinical observational study. Weights were repeatedly measured in 147 women with breast cancer stages I-III. Hierarchical linear modelling was used to analyse these longitudinal data. The overall pattern of weight change was a cubic form beginning with a mean of 56·9 kg before chemotherapy. It gradually increased to 59·4 kg at 8·5 months after the first chemotherapy followed by a decrease to 58·5 kg at 21·5 months. During the last 2·5 months, weight increased slightly and never returned to the initial level. After controlling for confounders, steeper weight change was observed among women receiving cyclophosphamide, methotrexate and fluorouracil. The highest weight gain in the cyclophosphamide, methotrexate and fluorouracil group was 2·9 kg (5%) vs. 0·9 kg (1%) in the anthracycline-based group. The trajectory of body weight change within two years after chemotherapy shows a trend of gradual ascent, followed by a small decline and a slight increase in the last 2·5 months. The chemotherapy regimen can predict the trend after controlling for other confounders; women on cyclophosphamide, methotrexate and fluorouracil have a steeper weight change. Nurses can inform women with breast cancer about the expected changes in body weight after chemotherapy to reduce their uncertainty. Future studies on effective interventions to minimise chemotherapy-induced weight gain are needed.

Drugs of abuse as memory modulators: a study of cocaine in rats

It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized. To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning. Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, × 5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift. Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning. Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.

Effectiveness of inhaled tobramycin in eradicating Pseudomonas aeruginosa in children with cystic fibrosis

Inhaled tobramycin therapy has been shown to be efficacious in clinical trials for the eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis (CF). However, the effectiveness of different regimens in eradicating P. aeruginosa and preventing the development of chronic infection in actual clinical settings has yet to be determined. This was an observational study of children (<18 years of age) with CF with incident P. aeruginosa infection from 2005-2012 based on data collected from the Toronto CF Database and medical charts. Patients who received inhaled tobramycin (80 mg/2 ml twice daily for 365 days) were compared to those who received tobramycin inhalation solution (TIS) (300 mg/5 ml twice daily for 28 days) with respect to eradication and development of chronic infection. We also examined the risk factors for recurrence of infection. During the study period, 65 patients were identified with incident P. aeruginosa, of which 7 (11%) failed eradication therapy. Eradication failure was similar between the two treatment groups. A total of 4 patients (6%) developed chronic P. aeruginosa infection in the 12 months following the end of therapy with no differences between treatment groups. Female gender, older age, pancreatic insufficiency, lower lung function and worse nutritional status were identified as risk factors for recurrence of P. aeruginosa infection. Both regimens of inhaled tobramycin have similar effectiveness in eradicating P. aeruginosa and preventing chronic P. aeruginosa infection in CF patients in clinical practice. Further work is needed, however, to identify patient characteristics and bacterial factors that play a role in eradication failure, in order to develop more effective antimicrobial rescue treatment strategies.

Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women

Background It is now recognized that Cimicifuga foetida extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. This paper compares the clinical effects of different regimens of three-month course on climacteric symptoms in Chinese women, so as to evaluate the efficacy and safety of Cimicifuga foetida extract. Methods This was a prospective, randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into 3 groups to take different kinds of medicine for 3 months; participants were given Cimicifuga foetida extract daily in group A (n=32), given estradiol valerate and progesterone capsule cycle sequentially in group B (n=32), and given estradiol valerate and medroxyprogesterone acetate cycle sequentially in group C (n=32). The questionnaires of Kupperman menopause index, Menopause-Specific Quality of Life, and Hospital Anxiety and Depression Scale were finished before and after the treatment. The status of vaginal bleeding and breast tenderness was recorded every day. Results Eighty-nine participants (89/96, 92.7%) completed the treatment. Kupperman menopause index decreased after taking the medicine for 3 months in each group (with all P&lt;0.001), but the score after the treatment was higher in group A than in the other 2 groups. Except for the score of sexual domain in group A (P=0.103), the scores of all domains of the Menopause-Specific Quality of Life decreased significantly after the treatment in all groups (with all P≤0.01). Score of anxity decreased significantly in group A (P=0.015) and B (P=0.003). Incidence of breast tenderness was 12.9% (4/31) in group A, 36.7% (11/30) in group B, and 14.3% (4/28) in group C. Incidence of vaginal bleeding was 6.5% (2/31) in group A, 26.7% (8/30) in group B, and 82.1% (23/28) in group C. Conclusions Cimicifuga foetida extract is effective and safe in the treatment of menopausal syndrome. It is worth extending its use in the treatment of climacteric complaints, especially among those having contradiction for hormone replacement therapy.

PWE-047 A Prospective, Comparative Audit of Two Commonly Used, Low Volume Bowel Preparations for Routine Colonoscopy: Moviprep Versus a Senna and Citramag Combination

IntroductionColonoscopy is the principal therapeutic tool for colorectal cancer prevention. Adenoma removal has been shown to decrease the incidence of colorectal cancer in screened populations. Good visualisation of the entire...

Морфологические изменения хориоретинального комплекса кролика непосредственно после воздействия различных режимов высокочастотной электросварки биологических тканей по сравнению с пороговой диодной эндолазерной коагуляцией

<p style="text-align: justify;"><span style="color: #800000;"><span style="font-size: 13.0080003738403px; line-height: 1.538em;"><span style="color: #800000;">https://doi.org/10.31288/oftalmolzh201336670</span></span></span>

Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: A comparative randomized assessment of different regimens

To compare the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome. A total of 60 patients (age 16-77 years) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospective, randomized study. A total of 30 patients were assigned to receive four weekly intravesical instillations of 40 mg of hyaluronic acid followed by five monthly instillations (hyaluronic acid-9 group). Another 30 patients received 12 intravesical instillations of 40 mg hyaluronic acid every 2 weeks (hyaluronic acid-12 group). Symptomatic changes after hyaluronic acid treatments were assessed using Interstitial Cystitis Symptom and Problem Indexes, pain visual analog scale, functional bladder capacity, frequency and nocturia in voiding diary, maximum flow rate, voided volume, postvoid residual volume, and Quality of Life Index at 1, 3 and 6 months. Of the 60 patients, 59 were evaluable at the end of the study. The Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and total score, pain visual analog scale, functional bladder capacity, maximum flow rate, and Quality of Life Index improved significantly after 6 months in both groups. The frequency and voided volume improved significantly only in the hyaluronic acid-12 group. However, patients with moderate and marked improvement were clinically similar in both groups. The measured variables did not differ between the two groups over the course of the study. No significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients. Both groups showed significant improvement in symptom scores and Quality of Life Index.

Effectiveness of different regimens of a collective topical treatment using a solution of copper and zinc chelates in the cure of digital dermatitis in dairy farms under field conditions

A controlled field trial was conducted to evaluate in dairy cattle the benefit provided by different regimens of a collective topical treatment using a solution of copper and zinc chelates to cure digital dermatitis (DD) compared with individual treatment alone, and further to investigate factors that could explain variations in the clinical cure of DD lesions over 6mo. The study was conducted between November 2009 and October 2010 and involved 4,677 dairy cows from 52 French dairy farms on which DD was endemic. The farms were quasi-randomly allocated to 1 of 4 treatment regimens for 6mo: no collective treatment (control), walk-through footbath during 4 consecutive milkings every 4 wk (FB/4W) or every 2 wk (FB/2W) and collective spraying during 2 milkings every 2 wk (CS/2W). For ethical and welfare reasons, all farmers also had to treat all detected active DD lesions with individual topical spraying of oxytetracycline. Digital dermatitis and leg hygiene were scored on all lactating cows during milking 7 times every 4 wk by 14 trained investigators. During these farm visits, data related to farm management were also collected. The curative effectiveness of collective treatments was assessed through a Cox survival frailty model as the probability of cure of an active DD lesion during at least 2 consecutive visits. The model was adjusted for farm and cow risk factors as well as initial DD prevalence. Monthly DD cure rates were 58, 55, 76, and 76% in the control, FB/4W, FB/2W, and CS/2W regimens, respectively. The spontaneous monthly cure rate for untreated active DD lesions was 61%. Hazard of cure of DD was increased by 1.28 and 1.41 when walk-through footbath and collective spraying, respectively, were applied over 2 d every 2 wk compared with the control regimen. Applying a walk-through footbath 2 d every 4 wk was not sufficient to improve the cure of DD compared with individual treatments alone. Three main factors were identified as speeding DD healing: cleanliness of the feet, initial small size of the DD lesion, and additional individual topical treatment. Grazing tended to speed DD healing. These results highlight the need of combining several control measures, including individual and collective topical treatments, and improving foot hygiene and the early detection of DD lesions to ensure a high cure rate and rapid curing of digital dermatitis on endemically affected farms.

Various doses of fractioned irradiation modulates multidrug resistance 1 expression differently through hypoxia-inducible factor 1α in esophageal cancer cells

To evaluate the effect of different regimen of radiotherapy on multidrug resistance 1 (MDR1) expression and analyze the role hypoxia-inducible factor 1α (HIF1α) played in the whole process. Fifty-four cell lines established from 96 esophageal cancer biopsy samples were given various doses of fractioned irradiation. The mRNA and protein levels of HIF1α and MDR1 post-irradiation were measured by quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. HIF1α-siRNA was used to verify the effect of HIF1α on radiation-mediated MDR1 modulation. In esophageal cancer cells surviving 28 Gy irradiation (2 Gy/f, 14 fractions), MDR1 mRNA expression increased 65.27 ± 5.58%, and HIF1α was elevated by 27.21 ± 2.25%. Interestingly, their expression decreased by 54.38 ± 11.53% and 32.08 ± 4.75% after 7 Gy irradiation (0.5 Gy/f, 14 fractions). HIF1α expression showed a positive correlation with MDR1 expression in the whole process (P < 0.05). Silencing of HIF1α decreased MDR1 expression and blocked changes in MDR1 and HIF1α expression induced by fractioned irradiation. These results indicate that MDR1 is differentially modulated by different doses of fractionated radiation, which should be taken into account when combining radiotherapy and chemotherapy for patients with esophageal cancer.

Prime immunization with rotavirus VLP 2/6 followed by boosting with an adenovirus expressing VP6 induces protective immunization against rotavirus in mice

BackgroundRotavirus (RV) is the main cause of severe gastroenteritis in children. An effective vaccination regime against RV can substantially reduce morbidity and mortality. Previous studies have demonstrated the efficacy of virus-like particles formed by RV VP2 and VP6 (VLP2/6), as well as that of recombinant adenovirus expressing RV VP6 (rAd), in eliciting protective immunities against RV. However, the efficacy of such prime-boost strategy, which incorporates VLP and rAd in inducing protective immunities against RV, has not been addressed. We assessed the immune effects of different regimens in mice, including rAd prime-VLP2/6 boost (rAd+VLP), VLP2/6 prime-rAd boost (VLP+rAd), rAd alone, and VLP alone.ResultsMice immunized with the VLP+rAd regimen elicit stronger humoral, mucosal, and cellular immune responses than those immunized with other regimens. RV challenging experiments showed that the highest reduction (92.9%) in viral shedding was achieved in the VLP+rAd group when compared with rAd+VLP (25%), VLP alone (75%), or rAd alone (40%) treatment groups. The reduction in RV shedding in mice correlated with fecal IgG (r = 0.95773, P = 0.04227) and IgA (r = 0.96137, P = 0.038663).ConclusionsA VLP2/6 prime-rAd boost regimen is effective in conferring immunoprotection against RV challenge in mice. This finding may lay the groundwork for an alternative strategy in novel RV vaccine development.

“The Lower the BP the Better” Paradigm in the Elderly

If a man will begin with certainties, he shall end in doubts; but if he will be content to begin with doubts, he shall end in certainties.— —Francis Bacon, The Advancement of Learning, year 1605 Hypertension is a growing public health problem in elderly people, with a prevalence up to 80% in individuals aged ≥70 years. Isolated systolic hypertension accounts for 60% to 75% of cases, systolic blood pressure (BP) being the dominant prognostic marker.1 Unfortunately, the rate of hypertension control only minimally improved over last year’s in elderly subjects when compared with the younger people.2 Several randomized clinical trials tested the benefit of treatment in elderly patients with isolated systolic hypertension or systolic-diastolic hypertension. Staessen et al3 reviewed 8 randomized clinical trials carried out in patients with isolated systolic hypertension and aged ≥60 years. Active treatment reduced total mortality by 13%, cardiovascular (CV) mortality by 18%, all CV complications by 26%, stroke by 30%, and coronary events by 23%. The benefits of treatment in octogenarians remained unproved for years up to the results of the Hypertension in the Very Elderly Trial, in which 3845 patients aged ≥80 years with systolic BP ≥160 mm Hg were randomized to indapamide or placebo. Perindopril or matching placebo was added if necessary to achieve the target BP of 150/80 mm Hg. The trial was stopped after less than 2 years of follow-up because of a beneficial effect of treatment on several outcomes including all-cause mortality, although the primary study outcome, fatal or nonfatal stroke, was only marginally reduced (by …

Corticosteroid regimens for treatment of acute and chronic graft versus host disease (GvHD) after allogenic stem cell transplantation.

Corticosteroids are commonly used in treatment of acute and chronic graft-versus-host disease (GvHD). Nevertheless, there has been no systematic analysis of effects of their use on the patients' survival and quality of life. To compare the effect of corticosteroids in treatment of patients with GvHD and to compare the effect of different regimens of corticosteroids. We searched MEDLINE (up to July 2008), EMBASE (up to July 2008) and the Cochrane Controlled Trials Register (up to July 2008) to identify relevant studies. All of the references were assessed in order to identify additional trials. Randomized controlled trials of any language were included in the study as long as they met any of the predefined comparisons of interest. The primary outcome in question was the overall survival of the patients. Due to lack of evidence, inclusion criteria was revised during the process of the review to include studies comparing different dosage of corticosteroids. All derived citations and abstracts were screened by two independent review authors for relevance. For the potentially relevant trials, the full text was obtained and reviewed by two review authors independently. Two review authors completed data extraction independently. After revising the inclusion criteria, this process was retried to ensure all relevant evidence is included in the review. No studies met the original inclusion criteria but two studies (four articles) met the revised inclusion criteria. As they addressed different clinical questions, meta-analysis was not performed. The outcomes of one study were in favor of efficacy of corticosteroids in inducing an earlier remission of acute GvHD, while the other study reported that early corticosteroid therapy of acute GvHD could not prevent progression of the disease to higher grades, although it was accompanied by a slightly better prognosis in the patients who responded by the fifth day of treatment. There is no certain study regarding appropriate use, dose and length of therapy for acute GvHD. Further studies are needed to define the appropriate use of steroids and whether other agents are appropriate as frontline therapy.

Need for a Point-of-Care Assay for Monitoring Antiplatelet and Antithrombotic Therapies

Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP Section Editors: The Framingham studies instituted by the National Institutes of Health in the 1950s identified the major risk factors for the development of cardiovascular disease. Specific lipid-lowering drugs and a variety of blood pressure-lowering drugs were developed to better mange these cardiovascular disease risk factors. Along with the use of these therapeutic modalities, the means to monitor risk factors after medical intervention was also developed. However, despite the fact that antiplatelet therapies are in use for a lot longer than statin therapy, no simple, specific, cost-effective assays are available for monitoring antiplatelet therapy. The need for such an assay for monitoring antithrombotic therapies is greater in patients with stroke. According to the American Heart Association update,1 on an …

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: Meta-analysis of randomised trials

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: Meta-analysis of randomised trials

A Virtuous Cycle to Improve Hypertension Outcomes at a National Level

Compared with the seemingly orderly approach to science associated with controlled laboratory environments, the assessment of broad changes in clinical practices and their impact on society is maddeningly complex and difficult to ascertain with confidence. Yet, in the end, the favorable regard of most societies toward public funding of biomedical science hinges on the belief that the end product of such research will benefit human health. This critical societal trust has been eroded by a growing skepticism directed toward the biomedical research enterprise and its associated industries, particularly the pharmaceutical industry. In this issue of Hypertension , Campbell et al1 report on their analysis of the impact of a program to improve the treatment of hypertension across Canada, one that has corresponded with increased use of antihypertensive medications and reduced incidence of death, stroke, myocardial infarction, and heart failure. The authors took advantage of the confluence of a major change in guideline recommendations, concerted national efforts linking professional societies and public health to control hypertension, and excellent sources of public data. These data allowed them to track prescriptions written by Canadian physicians and to correlate them with rates of key events (death and major cardiovascular and neurologic events) in the overall population. Using the powerful statistical technique of time series analysis, they demonstrated that rates of these critical events declined in direct proportion to the increase in prescription of antihypertensive medications, beginning in 1999. Taken at face value, this study provides compelling evidence that broad changes in medical care, when supported by convincing evidence from clinical trials, can result in improvements in death and disability for populations at the national level. Skeptics will …

Review: Blood pressure–lowering drugs prevent cardiovascular events equally well in younger and older patients

Source Citation Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-an...

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials

Objective To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults.Design Meta-analyses and meta-regression analyses used to compare the effects on...

Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts: a systematic review

Systemic antibiotics and antibiotic-impregnated shunt (AIS) systems are often used to prevent shunt infection. The authors conducted a systematic review to evaluate its effectiveness of antibiotics in patients who underwent placement of intracranial ventricular shunts. The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, and the meeting proceedings from the American Association of Neurological Surgeons and from the European Association of Neurosurgical Societies until June 2005. Randomized and quasi-randomized trials comparing the use of prophylactic antibiotics (either systemic or AIS systems) in intracranial ventricular shunt procedures with placebo or no antibiotics were included in the review. Seventeen trials involving 2134 patients were included. Results from the meta-analysis showed that the use of systemic antibiotic prophylaxis for internal shunts was associated with a decrease in shunt infection (odds ratio 0.51; 95% confidence interval 0.36-0.73). The authors found no significant differences between the subgroups evaluated in type of internal shunt (ventriculoperitoneal/ventriculoatrial), age, or duration of the administration of antibiotics. The authors found a benefit of systemic prophylactic antibiotics in preventing shunt infection, regardless of the patient's age and the type of internal shunt used. The benefit of its use after the first 24 hours postoperatively remains uncertain. Future trials should be conducted to evaluate the effectiveness of different regimens of systemic antibiotics rather than placebo, namely single preoperative dose versus multiple doses. It should also be mandatory to evaluate the effectiveness of systemic prophylactic antibiotics for external ventricular drains. Evidence suggests that antibiotic-impregnated catheters reduce the incidence of shunt infection, although more well-designed clinical trials are needed.

Recombinant human erythropoietin attenuates hepatic injury induced by ischemia/reperfusion in an isolated mouse liver model

Apoptosis is a central mechanism of cell death following reperfusion of the ischemic liver. Recombinant human erythropoietin (rhEPO) have an important role in the treatment of myocardial ischemia/reperfusion (I/R) injury, by preventing apoptosis. The aim of the study was to investigate the effect of different regimens of rhEPO in preventing apoptosis following I/R-induced hepatic injury. Isolated mouse livers were randomly divided into five groups: (1) control group, perfused for the whole study period (105 min); (2) 30-min perfusion followed by 90 min of ischemia and 15 min of reperfusion; (3), (4) and (5) like group 2, but with administration of rhEPO 5,000 units/kg i.p. at 30 min, 24 h, or both 30 min and 24 h respectively, before induction of ischemia. Perfusate liver enzyme levels and intrahepatic caspase-3 activity were measured, and apoptotic cells were identified by morphological criteria, TUNEL assay, and immunohistochemistry for caspase-3. Using immunoblot the expression of the proapoptotic JNK and inhibitor of NFkappaB (IkappaBalpha) were also evaluated. von Willebrand factor (vWF) immunohistochemistry was used as a marker of endothelial cells. Compared to the I/R livers, all 3 rhEPO pretreated groups showed: a significant reduction in liver enzyme levels (P < 0.05) and intrahepatic caspase-3 activity (P < 0.05), fewer apoptotic hepatocytes (P < 0.05) and positive vWF staining in numerous endothelial cells lining the sinusoids. EPO decreased JNK phosphorylation and the degradation of the inhibitor of NFkappaB (IkappaBalpha) during I/R. There was no added benefit of the multiple- over the single-dose rhEPO regimen. Pretreatment with one dose of rhEPO can attenuate post-I/R hepatocyte apoptotic liver damage. NFkappaB and JNK activation is likely to play a pivotal role in the pathophysiology of I/R hepatic injury and might have a key role in EPO-mediated protective effects. This effect is associated with the increase in sinusoidal vWF immunostaining suggests an additional effect of rhEPO in liver angiogenesis recovery. These findings have important implications for the potential use of rhEPO in I/R injury during liver transplantation.