Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system

Erythropoietin(EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.     

Prostatitis and male factor infertility: A review of the literature

Prostatitis and male infertility are frequent disorders, and the role of prostatitis in male infertility has been under discussion for more than 30 years. Many researchers have shown relevant links between the two. Although a causal relationship has not been definitely demonstrated, increasing evidence shows that chronic prostatitis has a relevant negative impact on male fertility potential, at least in certain subgroups. In the following review, we focus on the present state of knowledge on the role of chronic prostatitis as an etiologic factor in male infertility.     

Acetabular blood flow during Bernese periacetabular osteotomy: an intraoperative study using laser Doppler flowmetry.

BACKGROUND: The blood flow to the acetabular fragment is of some concern in juxtaarticular pelvic osteotomies used for the treatment of hip dysplasia. No direct measurements have determined the effect of the Bernese periacetabular osteotomy (PAO) on acetabular perfusion. METHODS: Acetabular perfusion was measured by means of laser Doppler flowmetry in 10 patients undergoing a PAO for symptomatic acetabular dysplasia. During the surgical procedure, the intraosseous high energy laser Doppler reliably depicts dynamic changes of small vessel blood flow. Measurements were performed after defined surgical steps to obtain sequential information on the blood perfusion of the acetabular fragment. RESULTS: After complete separation of the acetabular fragment, nine out of 10 patients had pulsatile signals, but the blood flow (BF) significantly decreased by 77%. Corrective positioning of the fragment induced no further drop of the BF signal but a loss of pulsatility in six patients. After a recovery period of about 30 min following preliminary fixation of the fragment, reestablishment of the pulsatile signal and an increase of the BF signal was seen. At termination of the surgical procedure, five out of eight patients, who could be followed throughout the whole procedure, showed a clear pulsatile signal in the supraacetabular area. Bleeding of the supraacetabular cancellous surface could be observed in all acetabula. CONCLUSION: Despite careful preservation of soft tissues during the surgical procedure, a significant reduction of the blood flow in the supraacetabular region has been observed. Nevertheless, a pulsatile signal in more than 60% of the fragments after fragment correction and an increasing signal during the recovery period showed ongoing blood perfusion indicating reversible changes in the measured supraacetabular area. All osteotomies healed within eight weeks without showing signs of necrosis during a minimum follow up of 1 year.     

Discriminative conditioning-related slow potential and single-unit responses in the frontal cortex of urethane-anesthetized rats

A model is described for obtaining long-term and stable discriminative conditioning-related slow-potential and single-unit responses from the frontal cortex of urethane-anesthetized rats. Responses were recorded and analyzed to reinforced (rewarding medial forebrain bundle stimulation) and non-reinforced tone cues. In the present study, cortical event-related slow potentials provided an adequate index of the level of discriminative conditioning. Single-unit response patterns are described for 57 neurons which demonstrated a discriminative response to either the reinforced or non-reinforced tone cue.     

Fatty acids platelets and oxidative markers following intravenous n-3 fatty acids administration in cystic fibrosis: An open pilot observational study.

BACKGROUND: An imbalance in the ratio of arachidonic acid and docosahexaenoic acid (DHA) was found in cystic fibrosis (CF) affected tissues and was suggested to promote inflammation. Several studies have shown that the long chain n-3 fatty acids reduced inflammatory activity while others have highlighted prooxidant activity of DHA at high concentrations. The aim of our study was to evaluate the effects of an intravenous fish-oil emulsion enriched with n-3 FA in patients with CF on plasma and platelet FA composition and peroxidation markers. METHODS: 13 patients with CF received one IV emulsion per week of 2 mL/kg fish-oil n-3 emulsion for 12 weeks. RESULTS: There was a significant increase in 20:5 n-3 and 22:6 n-3 platelet FA composition, no variation in 20:4 n-6, a decrease in n-9. There was no variation in plasma FA composition. Specific urinary markers of lipid peroxidation derived from n-3 and n-6 showed a very high level before infusion compared with usual values in healthy subjects which was not affected by treatment. A significant weight loss and a decrease in reduced glutathione were observed in adult patients. CONCLUSIONS: The intravenous administration of n-3 FA in CF patients induced a significant modification in platelet FA composition but no modification of oxidative markers. However, the weight loss and the decreased level in reduced glutathione observed in adult patients may suggest a potential deleterious activity for some patients. Further studies are necessary to determine the optimal dose and route for long chain FA administration required to reach a potential beneficial effect.     

Thyroid Artery Erosion by Esophageal Cancer: Management with Interventional Radiology

Management of upper gastrointestinal bleeding because of erosion of vessels by esophageal cancer may be challenging. We present herein the angiographic images of a 49-year-old patient who was admitted with massive bleeding from a tumor-eroded inferior thyroid artery. Attempts to control the bleeding by means of flexible endoscopy and insertion of a Sengstaken–Blakemore tube had failed. The diagnosis was impressively demonstrated by multislice computed tomography with intravenous contrast in the arterial phase and multiplanar reconstructions (computed tomography angiography) and by digital subtraction angiography. The bleeding was successfully treated with superselective catheterization and coiling of the eroded vessel.     

Early Low-Grade Proteinuria: Causes, Short-Term Evolution and Long-Term Consequences in Renal Transplantation

Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1-3 months and 3-12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p<0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival.     

Epidemiological study on the hepatotoxicity of occupational toluene exposure

Summary In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine amino-transferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers.