TLR2, TLR4 and TLR9 polymorphisms and Crohn's disease in a New Zealand Caucasian cohort

BACKGROUND AND AIM: Toll-like receptors (TLRs) have been identified as susceptibility genes for Crohn's disease (CD) in some, but not all, studies. Here we examined the association between candidate disease-susceptibility polymorphisms in the TLR2, TLR4 and TLR9 genes and CD in a New Zealand Caucasian population. METHODS: The frequency of gene polymorphisms was examined in 182 CD patients and in 188 ethnically matched controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: We could not detect any significant difference in the allele frequencies of polymorphisms in the TLR2 (R753Q, 0.029 vs 0.016, P = 0.25), TLR4 (D299G and T399I, 0.085 vs 0.071, P = 0.49; and 0.085 vs 0.082, P = 0.90), and TLR9 (-1237T/C, 0.154 vs 0.148, P = 0.82) genes between controls and patients, respectively. There was no evidence that the variant TLR alleles were associated with disease phenotype. However, combination of the datasets of published studies with our dataset confirmed that the TLR4 polymorphism 299G (P = 0.0005; OR of 1.42 [95% CI 1.17-1.74]) and the TLR9 polymorphism -1237C (P = 0.0416; OR of 1.33 [95% CI 1.01-1.75]) are associated with CD. CONCLUSIONS: There was no evidence that the above variants of the TLR2, TLR4 and TLR9 genes are major risk factors for CD or influence disease phenotype in our New Zealand case-control study. Nevertheless, the significance of the TLR4 299G and TLR9-1237C associations with CD worldwide was confirmed by a meta-analysis test using our datasets and datasets from previously published studies.     

Development of ultra fast liquid chromatographic method for simultaneous determination of nitrendipine and carvone in skin diffusate samples

A simple and sensitive reverse phase ultra fast liquid chromatographic (UFLC) method for simultaneous determination of nitrendipine and carvone in skin diffusate samples and microemulsions was developed and validated. The separation was achieved using a gradient mobile phase, on an Onyx column. The eluents were monitored by photodiode array detection. The linearity ranges of proposed method were 0.125–50 μg mL⁻¹ and 0.125–30 μg mL⁻¹ for nitrendipine and carvone respectively. The intra-day and inter-day coefficient of variation and percent error values of the assay method were less than 10%. The method was found to be precise, accurate, and specific during the study. The method was successfully applied for simultaneous estimation of nitrendipine and carvone in ex vivo skin diffusate samples and microemulsions.     

Methamphetamine-induced neurotoxicity: the road to Parkinson’s disease

Studies have implicated methamphetamine exposure as a contributor to the development of Parkinson’s disease. There is a significant degree of striatal dopamine depletion produced by methamphetamine, which makes the toxin useful in the creation of an animal model of Parkinson’s disease. Parkinson’s disease is a progressive neurodegenerative disorder associated with selective degeneration of nigrostriatal dopaminergic neurons. The immediate need is to understand the substances that increase the risk for this debilitating disorder as well as these substances’ neurodegenerative mechanisms. Currently, various approaches are being taken to develop a novel and cost-effective anti-Parkinson’s drug with minimal adverse effects and the added benefit of a neuroprotective effect to facilitate and improve the care of patients with Parkinson’s disease. A methamphetamine-treated animal model for Parkinson’s disease can help to further the understanding of the neurodegenerative processes that target the nigrostriatal system. Studies on widely used drugs of abuse, which are also dopaminergic toxicants, may aid in understanding the etiology, pathophysiology and progression of the disease process and increase awareness of the risks involved in such drug abuse. In addition, this review evaluates the possible neuroprotective mechanisms of certain drugs against methamphetamine-induced toxicity.     

Can urinary excretion rate of malondialdehyde, uric acid and protein predict the severity and impending death in perinatal asphyxia?

Background

Perinatal asphyxia (PA) associated with multi-organ damage is a leading cause of neonatal mortality and morbidity. We evaluated if urinary malondialdehyde:creatinine (UMDA:Cr), uric acid:creatinine (UUA:Cr) and protein:creatinine (UP:Cr) vary with the severity of PA and if these parameters can predict the impending death in PA.

Methods

Study included 20 asphyxiated and 20 healthy newborn males. Hypoxic-ischemic encephalopathy (HIE) staging, APGAR (activity, pulse, grimace, appearance and respiration) score and urinary protein, uric acid, creatinine and MDA were evaluated.

Results

UMDA:Cr, UUA:Cr and UP:Cr were significantly higher and correlated with APGAR and HIE in PA. By regression analysis also, urinary parameters were found to have significant association with HIE stage and APGAR in PA. Receiver operating characteristics (ROC) curve of UP:Cr, UUA:Cr and UMDA:Cr showed area under curve of 0.896 (p = 0.003), 0.859 (p = 0.008) and 0.849 (p = 0.010) with cut-off value of 9.04 mg, 2.34 mg and 3.49 µg/mg of creatinine respectively that can optimally predict the impending death in PA. SDS-PAGE of unconcentrated urine detected both high (73 kDa and 68 kDa) and low molecular weight proteins (52 kDa, 47 kDa, 25 kDa and 20 kDa) in PA but not in controls.

Conclusion

Urinary excretion rate of uric acid, MDA and proteins is higher and has potential to act as biochemical markers for severity evaluation and death prediction in PA.     

Rationale for reading fluconazole MICs at 24 hours rather than 48 hours when testing Candida spp. by the CLSI M27-A2 standard method

We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.     

Amyloid beta peptides and glutamatergic synaptic dysregulation

Alzheimer's disease (AD) is a major neurodegenerative disorder in which overproduction and accumulation of amyloid beta (Abeta) peptides result in synaptic dysfunction. Recent reports strongly suggest that in the initial stages of AD glutamate receptors are dysregulated by Abeta accumulation resulting in disruption of glutamatergic synaptic transmission which parallels early cognitive deficits. In the presence of Abeta, 2-amino-3-(3-hydoxy-5-methylisoxazol-4-yl) propionic acid (AMPA) glutamate receptor function is disrupted and the surface expression is reduced. Abeta has also been shown to modulate N-methyl-d-aspartate receptors (NMDARs) and metabotropic glutamate receptors. The Abeta mediated glutamate receptor modifications can lead to synaptic dysfunction resulting in excitotoxic neurodegeneration during the progression of AD. This review discusses the recent findings that glutamatergic signaling could be compromised by Abeta induced modulation of synaptic glutamate receptors in specific brain regions.     

Outcome of neonates requiring assisted ventilation

Over a two-year period, we studied a total of 100 newborns delivered in our hospital, needing ventilation. The indications for ventilation, complications, outcome, and factors influencing outcome were analyzed. Of the 100 babies, 54 were preterm, 44 term and 2 post-term. Overall survival was 58%. The commonest indication for ventilation was meconium aspiration syndrome in term babies and hyaline membrane disease in preterms. Babies ventilated for pneumonia had the best outcome, while the poorest outcome was in sepsis. Survival increased significantly with increasing birth weight and gestational age. Downes score, Apgar score and pH at birth did not correlate significantly with outcome. The maximum peak inspiratory pressure requirement was significantly higher in the non-survivors. In pneumonia and sepsis, increased FiO2 requirement significantly impaired survival. The commonest complication was shock. Incidence of disseminated intravascular coagulation, pulmonary hemorrhage and pneumothorax was significantly higher in non-survivors; however, none of these factors was independently predictive of mortality.     

Management of congenital bilateral temporomandibular joint ankylosis with secondary mandibular hypoplasia

The aim of this article is to present the course of the condition in a case of congenital temporomandibular joint ankylosis that caused facial disfigurement, significant reduction of mouth opening, difficulty in feeding and breathing, and general interference with physical development.     

Is bleach-sedimented smear microscopy an alternative to direct microscopy under programme conditions in India?

This cross-sectional multi-centric study compared the yield of and potential benefit for detecting smear-positive pulmonary tuberculosis (PTB) by bleach sedimentation (2% sodium-hypochlorite) versus direct microscopy under programme conditions in India. Among 3168 PTB suspects, 684 (21.6%) were detected by bleach sedimentation vs. 625 (19.7%) by direct microscopy, with a proportional overall agreement of 96% (κ = 0.88). While 594 patients were smear-positive with both methods, 31 patients detected by direct microscopy were missed and an additional 90 patients were detected by bleach sedimentation. Overall, bleach sedimentation increased the yield of smear-positive TB detection; however; it also increased the time to results.     

Consumption of a mid-morning snack improves memory but not attention in school children

Muthayya, S., T. Thomas, K. Srinivasan, K. Rao, A. V. Kurpad, J.-W. Van Klinken, G. Owen and E.A. de Bruin: Consumption of a mid-morning snack improves memory but not attention in school children. Physiol Behav 00(0) 000-000, 2006.--This study aimed to determine whether consumption of a mid-morning snack with appropriate energy compensation through a smaller breakfast or lunch, resulted in improved cognitive performance of 7-9 year old children with a low and high socioeconomic status (LSES and HSES, n=35 and 34 respectively). The children were each randomly assigned to three iso-caloric dietary interventions: control (standard breakfast, no snack and standard lunch), intervention A (small breakfast, snack, and standard lunch) and intervention B (standard breakfast, snack, and small lunch), using a cross-over design. The children were tested on three different days, each one week apart. Computerised tests of cognitive performance, consisting of memory, sustained attention and psychomotor speed, were performed during four sessions, i.e., prior to breakfast, after breakfast, after a mid-morning snack and after lunch. Having a mid-morning snack resulted in a smaller decline in immediate and delayed memory in LSES but not in HSES children. Having a snack did not influence sustained attention and psychomotor speed in either LSES or HSES children. This study shows that a more evenly distributed energy intake throughout the morning by consuming a mid-morning snack improves memory performance in school-age LSES children even when the total amount of energy consumed during the morning is not altered.