Anticonvulsant activity of dapsone analogs. Electrophysiologic evaluation

BACKGROUND: In a previous study we reported that 4,4'diaminodiphenylsulfone (dapsone) has anticonvulsant activity using kainic acid (KA) model. This work shows the behavioral and electrophysiologic changes caused by systemic application of several dapsone derivatives. These derivatives include disodium salt of 4,4'-diaminodifenylsulfone N,N'-diformaldehyde sulfoxylate (I), 4,4'-diaminodiphenylsulfone N,N'-didextrose sulfonate (II), sodium dibisulfite 4,4'-biscinamilidenamindiphenyl sulfone (III), and N,N'-dimethyl-4,4'-dimethylphenylsulfone (IV), which were synthesized and purified in our laboratory. METHODS: A KA model was used to provoke limbic seizures. Limbic seizures were provoked by injection, KA, and electrophysiologic recorder at the following concentrations: 6.25 and 12.50 mg/kg of III and 6.25 and 12.50 mg/kg of IV. RESULTS: Compounds III and IV caused decrease of postdischarges; we found percentage of protection of 55.60 and 70.78%, respectively. This showed possible anticonvulsant activity of these compounds (III and IV), while I and II showed no significant changes. We also studied whether there was a dose-dependence relationship, and different doses of compound IV were evaluated (25.00, 12.50, 6.25, 3.12, and 1.62 mg/kg). We found that greatest anticonvulsant effect occurred using doses of 3.12 and 6.25 mg/kg (two of the three lowest doses). CONCLUSIONS: We concluded that IV at doses of 3.25 and 6.25 mg/kg has anticonvulsant effect because it diminished duration of the first limbic seizure induced by KA; latency of first limbic seizure crisis was also increased. Both facts demonstrated possible therapeutic application of compound IV as anticonvulsant.     

Vegetable consumption and carotenoids in plasma and adipose tissue in Malaga,Spain

OBJECTIVE: To study relationships between habitual dietary intake, adipose tissue concentrations of alpha-carotene, beta-carotene and lycopene, and plasma concentrations of alpha- and beta-carotene. DESIGN: Cross-sectional study including assessment of food habits by a food frequency questionnaire and 48-hour recall and determination of carotenoid concentrations in adipose tissue and plasma. SUBJECTS: 51 women (mean age of 62 years) from the control group of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Breast Cancer (EURAMIC), Málaga, Spain. RESULTS: In adipose tissue, beta-carotene was correlated with consumption of green pepper (r = 0.36; p < 0.05) and lycopene with total fruit/vegetable intake (r = 0.28; p < 0.05), green pepper (r = 0.31; p < 0.05), and carrot (r = 0.25; p < 0.10). In plasma, beta-carotene was correlated with total fruit/vegetable intake (r = 0.29; p < 0.10), lettuce (r = 0.34; p < 0.05), tomato (r = 0.26; p < 0.10), and lycopene with total fruit/vegetable intake (r = 0.27; p < 0.10). Age-, BMI- and waist circumference-adjusted regression coefficients for the regression of logn-transformed adipose and plasma concentrations on consumption of specific fruits and vegetables (per 100 g/day) were calculated. In adipose tissue, coefficients were: 1.50 (p < 0.05) for alpha-carotene/carrot; 1.90 (p < 0.10) and 0.51 (p < 0.10) for beta-carotene/green pepper and lettuce; 2.02 (p < 0.05), 1.25 (p < 0.05) and 0.18 (p < 0.05) for lycopene/green pepper, carrot and total fruit/vegetable intake. In plasma, coefficients were 1.14 (p < 0.05) and 0.21 (p < 0.05) for beta-carotene/lettuce and total fruit/vegetable intake. CONCLUSIONS: Consumption of fruit and vegetables could be linked directly to carotenoid concentrations in adipose tissue and plasma. Although associations with individual food items are related to their carotenoid contents, the absorption and distribution of carotenoids needs more attention to improve their usefulness as biomarkers of exposure.     

Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus

OBJECTIVE: To compare the results of medical treatment and antireflux surgery in patients with Barrett's esophagus (BE). SUMMARY BACKGROUND DATA: The treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question. METHODS: One hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1-18) in the medical treatment group and 6 years (range 1-18) in the surgical treatment group. RESULTS: Satisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery. CONCLUSIONS: These results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus.     

Trypanosoma cruzi poly-zinc finger protein: a novel DNA/RNA-binding CCHC-zinc finger protein

A poly-zinc finger protein, designated PZFP1 was identified in Trypanosoma cruzi for the first time. The protein has 191 amino acids, contains seven motifs Cys(X)(2)Cys(X)(4)His(X)(4)Cys. A recombinant PZFP1 was generated in E. coli and the expected 21kDa polypeptide co-purified with two other inducible products of about 42 and 63kDa. Western blot analysis of cell extracts using an anti-PZFP1 antibody recognized a major band of 41kDa. Electrophoretic mobility shift analysis demonstrated that both, recombinant and native PZFP1, specifically interact with single-stranded DNA or RNA oligonucleotides carrying recognition sequences of other CCHC proteins. The protein was localized mainly in the cytoplasm and nucleus as observed by indirect immunofluorescence analysis. PZFP1 interacted specifically with a T. cruzi serine-arginine-rich protein (TcSR) in a yeast two-hybrid assay, suggesting a role in pre-mRNA processing.     

Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats

BACKGROUND: Bacterial translocation plays an important role in the pathogenesis of spontaneous bacterial peritonitis mainly due to intestinal bacterial overgrowth. Alterations in the functional integrity of the intestinal barrier caused by an increased production of free radical metabolites as a consequence of portal hypertension could also facilitate bacterial translocation in cirrhotic rats. OBJECTIVE: The aim of the study was to determine intestinal mucosal lipid peroxidation and neutrophil infiltration and their relationship with portal hypertension and bacterial translocation in cirrhotic rats. DESIGN: Eighteen male Sprague-Dawley rats with cirrhosis induced by carbon tetrachloride, administered by gavage, and eight control rats were included in the study. METHODS: Samples of jejunum, ileum and caecum were obtained by laparotomy for the determination of malondialdehyde and myeloperoxidase as indexes of lipid peroxidation and neutrophil infiltration, respectively. Samples of ascitic and pleural fluids, mesenteric lymph nodes and ileal stools were obtained for the culture of microoganisms. RESULTS: The concentration of malondialdehyde was significantly higher in ileal and caecal, but not in jejunal mucosa, in cirrhotic rats, mainly in those with ascites (P< 0.01), as compared to control rats (P< 0.01), and in cirrhotic rats with bacterial translocation compared to those without bacterial translocation (P< 0.01). No differences between groups were observed in the concentrations of myeloperoxidase in jejunum, ileum or caecum. A direct correlation between ileal malondialdehyde and portal pressure was observed (P< 0.01). CONCLUSIONS: Cirrhotic rats, particularly those with ascites and bacterial translocation, show increased malondialdehyde levels in ileal and caecal mucosa. These results suggest that mucosal oxidative damage in ileum and caecum could favour bacterial translocation in cirrhotic rats.     

Two novel mutations in the muscle glycogen phosphorylase gene in McArdle's disease

We report on a Spanish family with myophosphorylase (EC 2.4.1.1) deficiency (McArdle's disease). The proband and his symptomatic sister were compound heterozygous for two novel mutations: a T-to-G transversion in exon 14 (c1722 T>G) that changes a tyrosine to a stop codon (Y573X), and a G-to-A transition in exon 15 (c1827 G>A) that disrupts the consensus signal at the donor splicing site. These findings further expand knowledge of the genetic bases of muscle glycogen phosphorylase deficiency.     

Stroke on awakening: looking for a more rational management

BACKGROUND AND PURPOSE: Stroke on awakening (SOA) is denied the benefits of thrombolytic therapy and is typically excluded from acute clinical trials on the grounds that the time of onset is unknown. In this study we compared the clinical characteristics of SOA and of stroke while awake (SWA), particularly in the subgroup of patients seen within a time frame of 6 h after stroke awareness. MATERIAL AND METHODS: Patients were included consecutively in the Stroke Data Bank of the Spanish Neurological Society (BADISEN) that records 365 different items, including vascular risk factors, neurological findings, stroke severity, aetiopathogenic diagnosis and neuroimaging data. RESULTS: A total of 1,248 patients with acute cerebral infarction were included in the study, 301 (24.1%) with SOA and 947 (75.9%) with SWA. The peak time for stroke occurrence was between 6:01 a.m. and 12 noon, both in the whole stroke group and in each aetiopathogenic stroke subtype. Age, sex, stroke risk factors, stroke severity at admission, vital signs and stroke subtypes were not significantly different between SOA and SWA, neither in the group as a whole nor in the group of patients seen within 6 h of stroke recognition. Six hundred and fifty-four patients were seen within the potential 6-hour therapeutic window. In this group, the CT scan on admission was normal in 39.4% of SOA but the ultimate CT/MRI scan showed that 46.2% of these had a territorial infarction (in SWA these same figures were 60.8 and 67.7%, respectively). CONCLUSION: There are no relevant differences in the clinical, neuroimaging and aetiopathogenic characteristics of SOA and SWA. We should rely on new techniques such as DWI/PWI to indicate the most appropriate treatment in a more rational manner as nearly half of the patients with SOA seen early may benefit from them.