Paroxysmal nocturnal hemoglobinuria in the differential diagnosis of thrombocytopenia

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease which diagnosis may be delayed due to variable clinical findings. We describe herein a case of PNH in a 21 year old woman who admitted with complaints of chronic weakness, intermittent spontaneous ecchymoses, and an intermittent abdominal pain. On laboratory tests thrombocytopenia and iron deficiency anemia without any clinical findings were found. Flow cytometric evaluations showed a PNH clone of 15% for erythrocytes, 64% for monocytes, and 60% for granulocytes. The patient was diagnosed with PNH and an eculizumab therapy was initiated. Following initiation of eculizumab therapy, the frequency of abdominal pain attacks decreased, hemoglobin level normalized, and platelet values increased slightly. In patients submitting with a triad of symptoms such as thrombocytopenia, iron deficiency anemia, and abdominal pain attacks of unknown etiology we suggest considering PNH. We also encourage physicians to share their similar observations in order to raise the knowledge on infrequent presentations of PNH

Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat

This study was designed to investigate the possible protective actions of nicotine on cerebrovascular permeability in convulsions during nicotine-induced seizures. We have measured the permeability changes in the blood-brain barrier (BBB) macroscopically and spectrophotometrically by using Evans blue dye. Specific gravity measurements were also performed to assess brain edema which develops after blood-brain barrier opening. The experiments were carried out on Wistar rats. Rats were divided into two groups. They received acutely a convulsive dose of nicotine 3, 5, 8 and 9 mg kg(-1) i.p. or pretreated with a low dose of nicotine (0.8 mg kg(-1) i.p.) for 21 days followed by the procedure mentioned in the first group. Acute nicotine injection induced a significant increase in blood pressure and Evans-blue passage, despite a decline in specific gravity values. Low doses of chronic nicotine administration markedly reduced both the leakage of dye, and brain water content. Chronic treatment with low doses of nicotine (0.8 mg kg(-1) day(-1) s.c.) lessened the intensity of tonic-clonic seizures observed with a single dose of 3, 5, 8 or 9 mg kg-l nicotine. The data presented here demonstrate that nicotine pretreatment results in decreased sensitivity to nicotine-induced seizures in rats. (C) 1999 Academic Press

THE CEREBROVASCULAR PERMEABILITY AND EPILEPSY - THE ROLE OF BLOOD-PRESSURE

This study was designed to evaluate the role of elevated blood pressure on cerebrovascular permeability and brain tissue specific gravity during epileptic seizures induced by Pentylenetetrazole (PTZ). The experiments were carried out on Wistar rats. Specific gravity was measured bilaterally in 10 regional brain areas and Evans-blue passage (across blood-brain barrier) was spectrophotometrically measured in 6 brain areas. Animals were divided into four groups: they received i.v. either saline, 80mg/kg PTZ (convulsive dose), 40mg/kg PTZ (subconvulsive dose) or 80mg/kg PTZ+phentolamine. 80 mg/kg PTZ induced significantly an increase in blood pressure, in specific gravity and in Evans-blue passage. 40mg/kg PTZ induced an increase in blood pressure and caused small changes in specific gravity but not in Evans-blue passage. The last group, in which the rise in blood pressure was prevented with Phentolamine, also showed a significant increase in brain specific gravity and in Evans-blue passage. The results clearly show that the increased blood pressure may contribute to but is not entirely responsible for the changes in the cerebrovascular permeability induced by epileptic seizures

Erythropoietin prevents the increase in blood-brain barrier permeability during pentylentetrazol induced seizures

Recombinant human erythropoietin (r-Hu EPO) has been shown to exert neuroprotection in ischemic, excitotoxicity, trauma, convulsions and neurodegenerative disorders. Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including neurodegenerative disorders. This study aimed to investigate the effects of r-Hu EPO on BBB integrity in pentylentetrazol (PTZ) induced seizures in rats. Seizures were observed and evaluated regard to latency and intensity for an hour. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage were observed for BBB integrity. r-Hu EPO was given intraperitoneally 24 h prior to seizure induction. Total seizure duration of 720 +/- 50 s after single PTZ administration (80 mg/kg i.p.) was declined to 190 40 s in r-Hu EPO pretreatment. A typical BBB breakdown pattern (i.e. staining in cerebellum, cerebral cortex, midbrain, hippocampus, thalamus and corpus striatum) was observed in rat brains with PTZ induced seizures; whereas, EPO pretreatment confined BBB leakage to cerebellum and cortical areas, and lessened the intensity of tonic-clonic seizures observed in PTZ seizures. The protective effect of r-Hu EPO on BBB permeability in seizures is a new and original finding. The protective action of r-Hu EPO in seizures and some of CNS pathologies warrant further investigations. (c) 2005 Elsevier Inc. All rights reserved

Chronic (3-Weeks) Treatment of Estrogen (17 beta-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine

Recently there has been a growing interest in the effects of estrogen on cognitive functions. In this study, we aimed to examine 17 beta-estradiol treatment on working and reference memory in ovariectomized rats. We also examined the changes in the acetylcholine (ACh) levels in the brain areas associated with learning and memory. The study was performed on Sprague-Dawley type 3-month-old female rats. The rats were divided into four groups as control, ovariectomy (OVX), and OVX and estrogen treatment (10 A mu g/day i.p. 17 beta-estradiol) groups for 3 (OVX + E3) and 21 days OVX + E21). The rats were trained on eight arm radial maze task with eight arms baited to assess spatial memory, in addition four arms baited to assess both working and reference memory performances. The electron microscope images of the ACh vesicles in the frontal cortex, temporal cortex and hippocampus areas of the brain which are important regions for learning and memory were screened. Results showed that long term 17 beta-estradiol treatment has positive effects on both reference memory and working memory and that ACh vesicles increased in the examined brain areas, especially in hippocampus. Our results suggest that 3 weeks 17 beta-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system

Passage of spermidine across the blood-brain barrier in short recirculation periods following global cerebral ischemia: effects of mild hyperthermia

Transport of a polyamine (PA), spermidine (SPMD) into rat brain at various early postischemic periods was studied. Rats underwent 20 min of four-vessel occlusion (4VO) followed by 5, 10, 30 and 60 min of recirculation (RC) periods with natural brain temperature. H-3-aminoisobutyricacid (AIB) and C-14-SPMD were utilised to search dual functions of the blood-brain barrier (BBB); barrier and carrier functions, respectively. Unidirectional blood-to-brain transfer constant (Kin) was calculated for AM and SPMD in four brain regions-parieto-temporal cortex, striatum, hippocampus and cerebellum. Kin for SPMD ranged between 1.2 +/- 0.3 x 10(3) ml g(-1) min(-1) (for striatum) and 2.2 +/- 0.4 x 10(3) ml g(-1) min(-1) (for cerebellum) in controls. Kin for AIB showed similar values. At 5 and 10 min RC periods, Kin for both substances increased in a non-specific manner in all brain regions studied. In the cortex, Kin for SPMD at 5 and 10 min RC periods were 3.2 +/- 0.4 x 10(3) and 2.9 +/- 0.3 x 10(3) ml g(-1) min(-1), respectively, and found to be maximum with respect to other brain regions studied. 30 and 60 min RC groups showed specific transport for SPMD, whilst there were no changes for Kin for AIB, in all brain regions studied. Hippocampus showed the maximum increase in Kin SPMD at 60 min RC (2.7 +/- 0.3 x 10(3) ml g(-1) min(-1)), corresponding to a percentage rise of 121%. Intraischemic mild brain hyperthermia (39 degreesC) gave rise to a striking increase in Kin at 60 min postischemia for both substances. These results suggest that there is a specific transport of SPMD into brain at 30 and 60 min RC periods following 20 min of forebrain ischemia. Moreover, dual functions of the BBB were perturbed with intracerebral mild hyperthermia during ischemia. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved

Nitric oxide involvement in seizures elicited by pentylentetrazol and sex dependence

It has been known that susceptibility to some types of epilepsy is affected by sex. In addition, the role of NO in epileptogenesis is still unclear; NO has been suggested to be either an anticonvulsive or a proconvulsive agent. In an attempt to elucidate both the role of NO and sex differences in sensitivity to seizures, male and female Wistar rats were treated intraperitoneally (i.p.) by pentylentetrazol (PTZ)( 80 mg/kg) and by a nitric oxide synthase( NOS) inhibitor N-omega-nitro-L-arginine-mthylester(L-NAME)(50mg/kg) and a NO precursor sodium-nitroprusside (SNP) (2.5mg/kg)-applied 15 min. before PTZ injection. Latency, frequency, severity, and duration of generalized clonic and clonic-tonic convulsions were recorded. Furthermore, alterations in severity, latency, frequency, and duration of convulsions were observed to correlate with NO. Both sexes, injected with PTZ, showed repetitive seizure patterns. Seizures were found to be more severe in females. L-NAME and SNP pretreatment produced paradoxical effects on PTZ- induced seizures in both sexes. L-NAME completely prevented PTZ- induced seizures in male rats, whereas increased severity, frequency, duration, and significantly shortened the latency in female rats. Unexpectedly, SNP increased convulsion severity, frequency, duration, and shortened latencies in male, whereas it decreased convulsion severity, frequency, and duration and prolonged latency in females. These results indicate that endogenous NO is involved in the regulation of convulsive action suggesting a role depending on sex

The prognostic effect of neutrophil-to-lymphocyte ratio and De Ritis ratio in glioblastoma multiforme patients

Abstract AIMS: Individuals with a higher De Ritis ratio (aspartate transaminase/alanine transaminase) and neutrophilto-lymphocyte ratio (NLR) have an inferior survival in varied malignancies. To our knowledge, the prognostic potential of the De Ritis ratio and NLR to predict the survival in nonmetastatic glioblastoma multiforme (GBM) patients remains unclear. In this study, we aimed to explore the prognostic power of the De Ritis ratio and NLR in patients with nonmetastatic glioblastoma multiforme. METHODS: Data of 262 patients with glioblastoma multiforme have been retrospectively analyzed. Their age, gender, tumor characteristics, AST/ALT ratio, NLR and hemogram values, including age at diagnosis and date of diagnosis were recorded. RESULTS: The median survival time of the study group was 21 months (95% CI: 19‒23 months). The first-year and second-year survival rates were 73.0% and 40.5%, respectively. The univariate analysis revealed that the correlation of survival with age, gender, left/right location of tumor, mean platelet volume and De Ritis ratio did not reach the level of significance. The univariate analysis of the prognostic potential of NLR indicated that a 1-unit increase in NLR value translates to a 1.05 times higher risk of death (95% CI: 1.01‒1.09). CONCLUSION: The results of this study lead to the observation that NLR value can serve as an effective prognostic marker in predicting the outcomes of patients with glioblastoma multiforme. It can be positioned as an easily accessible and cost-effective biomarker for establishing appropriate therapeutic strategies (Tab. 2, Fig. 1, Ref. 20)

An analysis of adjuvant treatment strategies in operated pancreatic cancer patients: An Izmir oncology group study

Background: Adjuvant treatment is necessary in pancreatic cancer patients, but the optimal approach is not clear yet. Our aim was to explore the effectiveness of adjuvant treatment modalities in patients with operated pancreatic cancer. Methods: There were five groups of patients operated for primary pancreas adenocarcinoma. The first two groups included patients who were treated with only adjuvant chemotherapy or radiotherapy. The patients in third group had received combination chemotherapy and radiotherapy either sequentially or concomitantly. The fourth group was composed of patients who were treated with adjuvant chemotherapy after concurrent chemoradiotherapy, whereas the patients in the fifth group were only observed after surgery without any adjuvant treatment. Results: There were 83 operated pancreatic cancer patients available for analysis. Median age of the patients was 63 years (range, 40-82 years). There were 55 patients who had local disease recurrence (n = 14) or metastasis (n = 41) during or after adjuvant treatment. The median overall survival for all patients was 14 months. When we compared the median survival of patients who had any adjuvant treatment with the patients treated without any adjuvant therapy, we found a significant statistical difference between the groups (32.4 vs 6.5 months; P = 0.000). In addition, survival of each treatment group was also compared with each other but we did not find any significant statistical difference. Conclusions: Our result suggests that any adjuvant therapy in the treatment of pancreatic cancer patients is important. However, we could not find any superiority between adjuvant treatment modalities

Antioxidant therapy in hemodialysis patients: A systematic review

Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinical outcomes (3 studies). The majority were small trials using a nonrandomized open-label design with a single HD group (no HD controls). Alpha-tocopherol was the most investigated antioxidant, with 20/25 studies reporting that this vitamin decreased oxidative stress, and one clinical outcome trial in 196 patients finding that it protected against secondary CVD. Studies using vitamin C were more equivocal, with 4/11 showing decreased oxidative stress and one clinical outcome trial showing no effect on morbidity or mortality. N-acetylcysteine was the most efficacious agent, with 4/4 studies indicating a decrease in oxidative stress and one trial (n = 134) showing reduced CVD events. Seven studies have used therapy containing a combination of antioxidants, with five of these reporting decreased oxidative stress. Most intervention studies in HD patients, such as statin therapy and increased dialysis dose, have failed to show improvement in CVD outcomes. Two intervention trials using different antioxidants have found CVD benefits, suggesting that this line of therapy is effective in this resistant population. These studies require validation in larger, adequately powered trials. Kidney International (2012) 81, 233-246; doi: 10.1038/ki.2011.341; published online 5 October 201