Evidence that oxymorphone-induced increases in micronuclei occur secondary to hyperthermia.

Oxymorphone is a potent opioid analgesic. Oral administration of oxymorphone to rats at doses >or= 20 mg/kg and mice at 500 mg/kg produced an increase in micronucleated polychromatic erythrocytes (MPCEs). Oxymorphone does not produce chromosome aberrations in vitro, suggesting that the increased MPCEs in vivo may involve indirect mechanisms. Opioids are known to affect thermoregulatory mechanisms. Changes in body temperature can increase the incidence of MPCEs in rodents. Studies were conducted to examine the relationship between increased MPCEs in rats given oxymorphone and changes in body temperature. Single oral doses of oxymorphone associated with increased MPCEs (20 and 40 mg/kg) also produced a marked, rapid increase in body temperature. When animals were pretreated with sodium salicylate, peak body temperature was lower and returned to baseline more quickly than when oxymorphone was given alone. MPCEs were evaluated in rats after administration of oxymorphone (40 mg/kg) alone or following pretreatment with an oral dose of sodium salicylate. Oxymorphone alone produced a statistically significant increase in the incidence of MPCEs (3.6 per 1000 polychromatic erythrocytes vs. 0.4 in controls). The number of MPCEs in animals pretreated with sodium salicylate was similar to controls. Sodium salicylate alone had no effect on the number of MPCEs. Systemic oxymorphone exposure was not affected by sodium salicylate pretreatment; maximum plasma concentration (C(max)) and area-under-the-curve values were similar after administration of oxymorphone alone or following pretreatment with sodium salicylate. These results indicate that the increased incidence of MPCEs following oxymorphone administration is directly related to increased body temperature.     

Disseminated neonatal herpes caused by herpes simplex virus types 1 and 2

Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2.     

Influence of Welding Speed on Fracture Toughness of Friction Stir Welded AA2024-T351 Joints

In order to ensure a quality welded joint, and thus safe operation and high reliability of the welded part or structure achieved by friction stir welding, it is necessary to select the optimal welding parameters. The parameters of friction stir welding significantly affect the structure of the welded joint, and thus the mechanical properties of the welded joint. Investigation of the influence of friction stir welding parameters was performed on 6-mm thick plates of aluminum alloy AA2024 T351. The quality of the welded joint is predominantly influenced by the tool rotation speed n and the welding speed v. In this research, constant tool rotation speed was adopted n = 750 rpm, and the welding speed was varied (v = 73, 116 and 150 mm/min). By the visual method and radiographic examination, imperfections of the face and roots of the welded specimens were not found. This paper presents the performed experimental tests of the macro and microstructure of welded joints, followed by tests of micro hardness and fracture behavior of Friction Stir Welded AA2024-T351 joints. It can be concluded that the welding speed of v = 116 mm/min is favorable with regard to the fracture behavior of the analysed FSW-joint.     

Pentadecapeptide BPC 157 Interactions with Adrenergic and Dopaminergic Systems in Mucosal Protection in Stress

Since superior protection against differentgastrointestinal and liver lesions and antiinflammatoryand analgesic activities were noted for pentadecapeptideBPC (an essential fragment of an organoprotective gastric juice protein named BPC), thebeneficial mechanism of BPC 157 and its likelyinteractions with other systems were studied. Hence itsbeneficial effects would be abolished by adrenal glandmedullectomy, the influence of different agents affecting, , and dopamine receptors on BPC 157gastroprotection in 48 h restraint stress was furtherinvestigated. Animals were pretreated (1 hr beforestress) with saline (controls) or BPC 157 (dissolved insaline) (10 g or 10 ng/kg body wt intraperitoneallyor intragastrically) applied either alone to establishbasal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneousadministration was carried out with various agents withspecific effects on adrenergic or dopaminergic receptors[given in milligrams per kilogram intraperitoneally except for atenolol, which was givensubcutaneously] phentolamine (10.0), prazosin (0.5),yohimbine (5.0), clonidine (0.1) (-adrenergicdomain), propranolol (1.0), atenolol (20.0)(-adrenergic domain), domperidone (5.0), and haloperidol(5.0) (peripheral/central dopamine system).Alternatively, agents stimulating adrenergic ordopaminergic systemsadrenaline (5.0) or bromocriptine(10.0)-were applied. A strong protection, noted followingintragastric or intraperitoneal administration of BPC157, was fully abolished by coadministration ofphentolamine, clonidine, and haloperidol, andconsistently not affected by prazosin, yohimbine, ordomperidone. Atenolol abolished only intraperitoneal BPC157 protection, whereas propranolol affectedspecifically intragastric BPC 157 protection.Interestingly, the severe course of lesion developmentobtained in basal conditions, unlike BPC 157gastroprotection, was not influenced by the applicationof these agents. In other experiments, when adrenalineand bromocriptine were given simultaneously, a strong reductionof lesion development was noted. However, when appliedseparately, only adrenaline, not bromocriptine, has aprotective effect. Thus, a complex protectiveinteraction with both -adrenergic (e.g.,catecholamine release) and dopaminergic (central)systems could be suggested for both intragastric andintraperitoneal BPC 157 administration. The involvementof -receptor stimulation in BPC 157 gastroprotection appearsto be related to the route of BPC 157 administration.The demonstration that a combined stimulation ofadrenergic and dopaminergic systems by simultaneous prophylactic application of adrenaline(- and -receptor stimulant) andbromocriptine (dopamine receptor agonist) maysignificantly reduce restraint stress lesionsdevelopment provides insight for further research on the beneficial mechanism ofBPC 157.     

Trend in mortality after stroke with atrial fibrillation

Purpose

To evaluate trend in mortality in stroke associated with atrial fibrillation, we examined mortality trend after stroke with atrial fibrillation by calendar year period (1980-1984, 1985-1989, 1990-1994, 1995-1999, and 2000-2002). We estimated trends separately for each sex in unadjusted analyses. We also adjusted for age, comorbid conditions, and general trend in mortality in the background population.

Methods

We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used multivariate Cox proportional hazards regression analysis to estimate trend in mortality.

Results

Incident stroke with a previous or concomitant diagnosis of nonvalvular atrial fibrillation or flutter was diagnosed in 24,470 subjects (11,554 men and 12,916 women). During 34,405 years of observation, 9237 men died, and during 35,381 years of observation, 10,827 women died. The hazard ratio for mortality after stroke in the last 3-year period compared with the first 5-year period was .65 (95% confidence interval [CI], .61-.71) in men and .69 (95% CI, .64-.74) in women.

Conclusions

We observed a substantially better survival in men and women after stroke associated with atrial fibrillation or flutter in Denmark during the years 1980 to 2002. However, we could not control for changes in admission practice, diagnostic performance, or treatment.     

Hepatitis B and hepatitis C virus infection and outcome of hemodialysis and kidney transplant patients

AIM: A comparison of the outcome of hepatitis virus-positive and -negative kidney transplant and hemodialysis patients was the aim of this investigation. MATERIALS AND METHODS: The study involved 384 kidney transplant patients (67 HBsAg positive, 39 anti-HCV positive, 278 hepatitis negative), transplanted between 1987 and 2001, and 403 hemodialysis patients (128 HBsAg positive, 83 anti-HCV positive, 192 hepatitis negative) who had started hemodialysis and were referred to the kidney transplant waiting list during the same period. RESULTS: Hemodialysis patients were older than transplant patients. Comparison of the groups' survival rates, adjusted for patient age, showed that all kidney transplant patients survived longer than hemodialysis patients (p < 0.001). HBV infection had a negative impact on patient survival, especially in hemodialysis patients. HCV infection did not have a significant influence on patient survival. Cardiovascular disease was the main cause of death of all hemodialysis- and hepatitis-negative transplant patients. Liver failure was one of the leading causes of death in HBV-positive transplant patients. Mortality risk was higher for older patients, HBV-positive and -negative hemodialysis patients. CONCLUSIONS: Kidney transplantation offers longer survival for hepatitis-positive and -negative hemodialysis patients. HBV but not HCV infection had a negative impact on ESRD patient survival.     

AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C

We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G₂/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G₂/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells.     

Seasonal variation in stroke and stroke-associated mortality in patients with a hospital diagnosis of nonvalvular atrial fibrillation or flutter. A population-based study in Denmark

AIM: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. METHODS: We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980-2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. RESULTS: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07-1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. CONCLUSIONS: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.     

Treatment of thrombotic microangiopathies with plasma exchange

Thrombotic microangiopathy (TMA) is a syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever and renal dysfunction. This retrospective analysis sought to determine the clinical characteristics and outcome of patients with TMA treated with plasma exchange at the Department of Dialysis, University Hospital Zagreb. From 1982 to July 2005, 17 patients (10 male and 7 female, age ranging from 18 to 74 years) have been diagnosed with TMA. The most common presenting symptom was purpura in 76.5%, followed by neurologic disturbance in 70.5%, renal function abnormality in 41.1%, and fever in 29.4% of patients. Patients were treated with a daily plasma exchange, which was continued until the normalization of platelet count with minimal hemolysis. Plasma exchange treatment was first tapered and later discontinued with careful monitoring of laboratory parameters. Of the 17 patients, 13 achieved complete remission after 5-32 sessions, two had partial response, and two had no response and died of progressive disease. Four patients developed chronic relapsing TMA, and three of them progressed to end-stage renal disease. Survival at 1 year in our series exceeds 88%, but decreased with duration of follow-up. Overall, with the median follow up of 5 years, 6 patients died from consequences of TMA (35.3%); three with chronic TMA, and 2 in the acute phase of progressive disease. A 74-year old male who developed TMA after prostate cancer died from disseminated malignant disease. Our results demonstrate a high incidence of renal function abnormalities in patients with TMA at presentation, but also during long term follow-up. Development of end-stage renal disease was associated with poor prognosis. Further studies, long term follow-up and establishment of international registries are needed to clarify many dilemmas associated with the diagnosis, treatment and outcomes of patients with TMA.