Vagus nerve stimulation inhibits seizure activity and protects blood–brain barrier integrity in kindled rats with cortical dysplasia

AimsThis study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood–brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD).Main methodsPregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed.Key findingsKindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P < 0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus.SignificanceThe results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.     

Association of eNOS gene intron 4 a/b VNTR polymorphisms in children with nephrotic syndrome

To investigate the association of endothelial nitric oxide synthase gene intron 4 (eNOS4) polymorphisms with nephrotic syndrome, the eNOS4 genotypes were assessed in 161 children with nephrotic syndrome in comparison with 78 healthy subjects. We classified the children with nephritic syndrome into 2 groups: as steroid-sensitive nephrotic syndrome (SSNS) (n = 125) and steroid-resistant nephrotic syndrome (SRNS) (n = 36). The eNOS4 polymorphisms were analyzed by polymerase chain reaction. The frequencies of eNOS4 aa, ab and bb genotypes were 3%, 31%, and 66% in all the nephrotic syndrome groups, and 1%, 23%, and 76% in the control group (x² = 2.87, p > 0.05). In addition, the frequencies of eNOS4 aa, ab and bb genotypes were 2%, 33%, and 65% in SSNS group, and 5%, 28%, and 67% in the SRNS group (x² = 1.13, p = 0.567). The present study is the first to investigate eNOS4 gene polymorphisms in children with SSNS and SRNS. Our data show that the eNOS4 gene polymorphisms were not associated with the development, frequent relapse and response to steroid in nephritic syndrome.     

A new species of the genus Chaetopelma Ausserer, 1871 (Araneae: Theraphosidae) from Turkey

A new species of Chaetopelma Ausserer, 1871 is described from Hatay province, Turkey. Differences between the new species and related species are discussed. The characteristic features of this species are described and illustrated.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:99C21605-5308-4363-8420-02F6151B4457     

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.     

Synthesis, characterization and antimicrobial activity of new aliphatic sulfonamide

A series of novel aliphatic sulfonamide derivatives (1-7) were synthesized and characterized by elemental analyses, FT-IR, (1)H NMR, (13)C NMR and LC-MS techniques. All the synthesized compounds were evaluated in vitro as antimicrobial agents against representative strains of Gram-positive (Staphylococcus aureus ATCC 25953, Bacillus cereus ATCC 6633 and Listeria monocytogenes ATCC Li6 (isolate), Gram-negative bacteria (Escherichia coli ATCC 11230) and antifungal agent against Candida albicans (clinical isolate) by both disc diffusion and minimal inhibition concentration (MIC) methods. All these bacteria and fungus studied were screened against some antibiotics to compare with our chemicals' zone diameters. Our aliphatic sulfonamides have highest powerful antibacterial activity for Gram-negative bacteria than Gram-positive bacteria and antibacterial activity decreases as the length of the carbon chain increases.     

Zonisamide: Antihyperalgesic efficacy,the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy

Aims

The purpose of this study was to compare the changes of antihyperalgesic effectiveness of zonisamide (25 and 50 mg/kg), an antiepileptic drug, on the early and late phases of neuropathy and to investigate the role of serotonergic descending inhibitory pain pathways in antihyperalgesic effectiveness of zonisamide in the streptozotocin-induced rat model for painful diabetic neuropathy.

Main methods

The hot-plate and tail-immersion, to determine thermal thresholds, and paw pressure withdrawal tests, to determine mechanical thresholds, were performed as hyperalgesia tests. To investigate the role of serotonergic pathway, 1 mg/kg ketanserin (5-HT_2A/2C antagonist) and ondansetron (serotonin 5-HT₃ receptor antagonist) were used.

Key findings

Zonisamide enhanced pain thresholds significantly in the 3rd, 6th and 8th weeks as the reference drugs morphine (5 mg/kg) and carbamazepine (32 mg/kg, tested only in the 3rd week). There were no observed differences on the potency of antihyperalgesic effect between weeks and between doses. Each antagonist reversed the effect of zonisamide in the hot-plate and tail-immersion tests significantly, but, relatively in the paw pressure withdrawal tests.

Significance

These results support the role for zonisamide in the management of diabetic neuropathic pain in all phases. Serotonin 5-HT_2A/2C and 5-HT₃ receptors are involved in the antihyperalgesic effect of zonisamide by enhancement of thermal threshold, and partially by mechanical threshold, so they may not mediate mechanical hyperalgesia in diabetic neuropathy.     

Protective effect of esterified glucomannan on aflatoxin-induced changes in testicular function,sperm quality,and seminal plasma biochemistry in rams

The aim of this study was to determine the effect of aflatoxin (AF) on spermatologic, biochemical, and testis parameters in rams, and the protective efficiency of esterified glucomannan (EG) co-administered with AF. Thirty-two Merino rams (12–14 months old) were used. The experimental design consisted of four dietary treatments. The control group was fed commercial feed. The AF group was fed with commercial feed plus 250 μg/d of total AF. The EG group received commercial feed plus 2 g/d of EG. The AF + EG group was given commercial feed plus 250 μg/d of total AF and 2 g/d of EG. There were treatment, time, and treatment-by-time interaction effects on sperm motility, abnormal spermatozoa, damaged acrosome, and dead spermatozoa (P < 0.01). The percentage of motile sperm was lower and the percentages of abnormal sperm, sperm with damaged acrosomes, and dead sperm were greater in the AF group than in the control, AF+EG, and EG groups, as from week 3 until the end of week 12 (P < 0.05). As from week 3, hyaluronidase activity in the seminal plasma increased significantly in the AF group, compared with the control. The co-administration of AF+EG was found to be effective in preventing the increase in hyaluronidase activity. As week 4, malondialdehyde (MDA) levels were significantly higher in the AF group compared with the control. The combined administration of AF+EG was found to be effective in lowering the MDA levels, increased by AF, to the levels measured in the control (P < 0.05). Although glutathione (GSH) levels were determined to have significantly decreased in the AF group in comparison to the control, it was observed that, in the group co-administered with AF and EG, particularly after week 7, the GSH levels, which had decreased owing to AF, were largely ameliorated (P < 0.05). In conclusion, AF adversely affected spermatologic, biochemical, and testis parameters, and the combined administration of EG with AF reversibly eliminated these adverse effects in rams.     

Fosmid cloning, nucleotide sequence, and characterization of a beta-lactamase gene from subsurface isolates

A beta-lactamase gene was isolated for the first time from a terrestrial subsurface environment using a combined cultivation and direct cloning strategy. The gene, discovered from 24 m below land surface in Hawaii, was most similar to the penicillinase from Bacillus licheniformis. The resistance gene was confirmed via subcloning and its minimum inhibitory concentration values were measured against several test beta-lactam antibiotics. This study extends the knowledge on resistance to antimicrobials, which may help the efforts to minimize their future threat.     

The protection of selenium on adriamycin-induced mitochondrial damage in rat

Although adriamycin (ADR) exhibits high anti-tumor efficacy in vitro, its clinical use in cancer chemotherapy is limited due to its high renal toxicity. This study investigated the mechanism of ADR nephropathy and the protective effect of selenium on ADR-induced kidney damage by analyzing of the relationship between selenium and mitochondria. Rats were divided into four groups. The first group was injected with saline i.p. for 21 days, the second group received the 4 mg/kg i.p. ADR every alternate day for 8 days, the third group received the 50 μg/kg i.p. Se for 21 days, and the fourth group received the Se. ADR co-administration i.p. blood pressures were assessed, the mitochondrial membrane potential (MMP) was assessed, and the adenosine triphosphate (ATP) levels were determined. The total antioxidant (TAS) and oxidant status (TOS) in cytosol, the mitochondria of kidney cells, and plasma were measured. Mitochondrial TAS decreased and TOS increased in the ADR group compared to the Se group. ADR-treated rats showed significantly lower MMP than did the control and Se groups. MMP was significantly restored in the Se + ADR group through selenium treatment compared to the ADR group (p < 0.01). In the ADR group, a reduction in ATP content was seen compared to the control and Se groups (p < 0.01). ATP level was significantly restored through treatment with selenium in the Se + ADR group compared to the ADR group (p < 0.01). We concluded that selenium is effective in vivo against ADR-induced kidney damage via the restoration of TAS and TOS, which prevented mitochondrial damage.