Nitric oxide reversibly impairs axonal conduction in Guinea pig spinal cord

Increased expression of the inducible and neuronal isoforms of nitric oxide synthase (NOS), and elevated concentrations of nitric oxide (NO) metabolites, are present within the central nervous system (CNS) following neurotrauma and are implicated in the pathogenesis of the accompanying neurologic deficits. We tested the hypothesis that elevated extracellular concentrations of NO introduced by the donor Spermine NONOate, induce reversible axonal conduction deficits in neurons of the guinea pig spinal cord. The compound action potential (CAP) and compound membrane potential (CMP) of excised ventral cord white matter were recorded before, during, and after bathing the tissue (30 min) in varying concentrations (0.25-3.0 mM) of Spermine NONOate. The principal results were a rapid onset, dose-dependent, reduction in amplitude of the CAP (p < 0.05) accompanied by depolarization of the CMP during NO exposure. These effects were largely reversible on washout, at low concentration of the donor (0.5 mM), but were only partially reversed at higher concentrations. Changes in the electrophysiological properties were not evident when the donor had been a priori depleted of NO. The results extend previous reports that NO induces reversible axonal conduction deficits. They provide new evidence of dissociation of the effects of NO on CAP and CMP during washout, and after prolonged exposure to the donor. They add support to the emerging concept that immune-mediated axonal conduction failure contributes to reversible neurologic deficits following neurotrauma and aid in understanding clinical phenomena such as spinal shock and neurologic recovery.     

The effect of betamethasone and IFN-gamma on replication of Toxoplasma gondii (RH strain) and nitric oxide production in Hela cell culture

Toxoplasmosis is a protozoal infection caused by Toxoplasma gondii. Toxoplasmosis produce severe damage in patients who are immunosuppressed. In those who are immunosuppressed, latent infection can be reactivated resulting in acute disseminating disease. Betamethasone is a synthetic glycocorticoid, used as an anti-inflammatory and immunosuppressant in a wide variety of disorders. The aim of this study was evaluation of betamethasone as an immunosuppressor drug on infected cells by Toxoplasma gondii. In this study, at first HeLa cells were grown in 24 well culture plates in culture medium . When confluent monolayer was obtained, we compared 6 groups to evaluate the effect of betamethasone as a corticosteroid drug (two concentrations 4 and 40 micro g/ml) and the effect of IFN-gamma (100 IU/ml ) on growth, replication and Nitric Oxide (NO) production. The results showed, that high number of plaques were seen in group with 40 mug/ml of betamethasone and the lowest number of plaques were seen in group with 100 IU of IFN-gamma. The difference between plaque number in control and groups treated with IFN-gamma and betamethasone was significant (P<0.05). The groups with betamethasone or IFN-gamma without tachyzoites did not show any effect on cell structures. Replication rates in the wells treated with IFN-gamma were decreased significantly 72 h post inoculation in comparison with control group (P<0.05). There was no significant difference among different groups in NO production. The results indicated that betamethasone increase the invasion of tachyzoites to host cells in vitro.     

Surface area: a better predictor of disease severity than the height and volume of the barium column in patients with primary achalasia

OBJECTIVE: Subjective assessment of primary achalasia is not accurate. We aimed to study the utility of surface area of barium retention in the objective assessment of these patients. METHODS: Subjective and objective esophageal functions of 99 patients with primary achalasia were evaluated initially and 43 of them were reevaluated 1 month after balloon dilation. RESULTS: Before dilation: Ninety-nine patients were enrolled. Forty-one of them were male. The mean age was 37.5+/-15.3 years. The mean score, resting lower esophageal sphincter pressure, height, surface and volume of barium retention at 5 min were 8.03+/-3.1, 59.1+/-20 mmHg, 9.9+/-4.9 cm, and 23.6+/-13.9 cm and 53.2+/-47.7 cm, respectively. Surface area at 5 min had best correlation and predictive value for resting lower esophageal sphincter pressure. After dilation: Forty-three of 99 patients were reevaluated after balloon dilation. The mean age was 36.8+/-13.6 years. Seventeen of them were male. Mean score, resting lower esophageal sphincter pressure, height, surface area and volume of barium retention at 5 min dropped significantly after dilation. Surface area at 5 min had best correlation and predictive value for lower esophageal sphincter pressure. CONCLUSIONS: Surface area of barium retention at 5 min is an accurate objective tool to assess patients with primary achalasia. It is cheap and easy to perform; therefore, it could be used more frequently in postdilation follow-up.     

A haplotype framework for cystic fibrosis mutations in Iran

This is the first comprehensive profile of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and their corresponding haplotypes in the Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients were sequenced to identify disease-causing mutations. Eleven core haplotypes of CFTR were identified by genotyping six high-frequency simple nucleotide polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from the frequency of heterozygous patients and suggests that contrary to popular belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were identified on 64 (53%) of the 120 chromosomes. The five most common Iranian mutations together represented 37% of the expected mutated alleles. The most frequent mutation, DeltaF508 (p.F508del), represented only 16% of the expected mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at 7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not included in a commonly used panel of CF mutations, underscoring the importance of identifying geographic-specific mutations in this population.     

Influence of acute and sub-chronic nicotine pretreatment on morphine state-dependent learning

In the present study, the effects of acute and sub-chronic pretreatment of nicotine on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pre-training administration of morphine (5mg/kg) decreased the learning of a one-trial passive avoidance task, which was reversed by pre-test administration of the same dose of morphine. Amnesia induced by pre-training morphine was also significantly reversed in nicotine (0.001, 0.01 and 0.1 mg/kg)-treated animals on the test day. Morphine induced amnesia was also reversed in animals which had previously received sub-chronic injections of nicotine, once daily for 3 days followed by 14 days of no drug treatment. The restoration of memory by pre-test morphine was also reduced in animals which had previously received once daily injections of atropine (0.25, 0.5 and 1 mg/kg, i.p.) for 3 days after 14 of being days drug free. In the animals, restoration of memory by sub-chronic nicotine administration, was also decreased by once daily administration of atropine (0.25, 0.5 and 1 mg/kg) 10 min prior to injection of nicotine (0.1 microg/kg/day, for 3 days) but not with SCH 23390; R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl (0.01, 0.05 and 0.1 mg/kg) or sulpiride (25, 50 and 100 mg/kg) during 3-days of treatment with nicotine. The results suggest that nicotine may induce sensitization which affects the impairment of memory formation via cholinergic but not dopaminergic systems.     

Docking and CoMFA study on novel human CCR5 receptor antagonists

The CC-chemokine receptor 5 (CCR5), a membrane protein belonging to the G protein-coupled receptor super-family, has been identified as an essential co-receptor for HIV entry into the cells. Small molecules were used to inhibit HIV entry by targeting CCR5. In this study, comparative molecular field analysis (CoMFA) was carried out on 70 novel phenoxybenzyl derivatives as antagonists of CCR5 HIV co receptor. This CoMFA model yielded satisfactory statistical data with the cross-validated q ² of 0.611 and non-cross-validated r ² of 0.903. Mapping this model according to the topology of the active site of CCR5 end to a better understanding of antagonist-CCR5 interactions. Because of lacking crystallography structure of CCR5, the 3D structure from threading assembly refinement (TASSER) method was used. These antagonists were docked into the binding site of the 3D model of CCR5 using ligandfit, and the probable interaction model between CCR5 and the antagonists were obtained. The correlation of predicted binding affinities between antagonists and CCR5 has good statistical quality.     

Batch-related sterile endophthalmitis following intravitreal injection of bevacizumab

Background:

To report a series of patients with sterile endophthalmitis after intravitreal bevacizumab (IVB) injection from 2 different batches of bevacizumab.

Materials and Methods:

Records of 11 eyes with severe inflammation after IVB injections from two different batches (7 eyes from one and 4 from the other) on two separate days were evaluated. Fifteen eyes of 15 patients in one day were treated with one batch and 18 eyes of 17 patients were treated another day using another batch injected for different retinal diseases. Each batch was opened on the day of injection. We used commercially available bevacizumab (100 mg/4 ml) kept at 4°C. Severe cases with hypopyon were admitted to the ward and underwent anterior chamber and vitreous tap for direct smear and culture.

Results:

Pain, redness and decreased vision began after 11-17 days. All had anterior chamber and vitreous reactions and 5 had hypopyon. Antibiotics and corticosteroids were initiated immediately, but the antibiotics were discontinued after negative culture results. Visual acuity returned to pre-injection levels in 10 eyes after 1 month and only in one eye pars plana vitrectomy was performed. Mean VA at the time of presentation with inflammation (1.76 ± 0.78 logMAR) decreased significantly (P =0.008) compared to the initial mean corrected VA (1.18 ± 0.55 logMAR); however, final mean corrected VA (1.02 ± 0.48 logMAR) improved in comparison with the baseline but not to a significant level (P =0.159).

Conclusions:

We report a cluster of sterile endophthalmitis following intravitreal injection of bevacizumab from the same batch of bevacizumab that has a favorable prognosis.     

M-banding characterization of a 16p11.2p13.1 tandem duplication in a child with autism, neurodevelopmental delay and dysmorphism

We describe a partial duplication of the chromosome 16 short arm [46,XY,dup(16)(p11.2p13.1)] in an Iranian girl with autism, neurodevelopmental delay, mental retardation, very poor memory, and dysmorphism including sparse hair, upslanting palpebral fissures, long philtrum, micrognathia, hypotonia, small feet and hands, syndactyly of the fingers, and hypoplastic thumbs. The patient now four years old, has a normal twin sister, and the parents are unrelated. The abnormal 16p was originally detected by banding cytogenetic techniques, and was characterized by multicolour banding fluorescence in situ hybridization (MCB). The MCB pattern on the derivative chromosome 16 indicated a direct duplication of the region 16p11.2 to 16p13.1.