From tau to toxicity: emerging roles of NMDA receptor in Alzheimer's disease

Glutamate toxicity through NMDA receptor channels has long been central to the understanding of acute neuronal injury. Recent studies implicate similar events in chronic neurodegenerative diseases. Here, we analyze some of the most intriguing evidence for NMDA receptor-mediated cellular dysfunction and propose a mechanism by which hyperactive NMDA receptors might lead to neurofibrillary degeneration in Alzheimer's disease.     

Reasons for non-vaccination in pediatric patients visiting tertiary care centers in a polio-prone country

Background

The Expanded Program on Immunization (EPI) was initiated by World Health Organization (WHO) in 1974 in order to save children from life threatening, disabling vaccine-preventable diseases (VPDs). In Pakistan, this program was launched in 1978 with the main objectives of eradicating polio by 2012, eliminating measles and neonatal tetanus by 2015, and minimizing the incidence of other VPDs. However, despite the efforts of government and WHO, this program has not received the amount of success that was desired. Hence, the objectives of this study were to elucidate the main reasons behind not achieving the full immunization coverage in Pakistan, the awareness of children’s attendant about the importance of vaccination, their attitudes, thoughts and fears regarding childhood immunization, and the major hurdles faced in pursuit of getting their children vaccinated.

Methods

This was an observational, cross-sectional, questionnaire-based study conducted during a one year period from 4th January, 2012 to 6th January, 2013 at the pediatric outpatient clinics of Civil Hospital (CHK) and National Institute of Child Health (NICH). We attempted to interview all the parents who could be approached during the period of the study. Thus, convenience sampling was employed. The parents were approached in the clinics and interviewed after seeking informed, written consent. Those patients who were not accompanied by either of their parents were excluded from the study. The study instrument comprised of three sections. The first section consisted was concerned with the demographics of the patient and the parents. The second section dealt with the reasons for complete vaccination or under-vaccination. The last section aimed to assess the knowledge, attitudes and beliefs of the respondents.

Results

Out of 1044 patients, only 713(68.3%) were fully vaccinated, 239(22.9%) were partially vaccinated while 92(8.8%) had never been vaccinated. The vaccination status showed statistically significant association with ethnicity, income, residence, number of children and paternal occupation (p < 0.05 for all). The most common provocative factor for vaccination compliance was mass media (61.9%). The most common primary reason for non-vaccination was lack of knowledge (18.1%), whereas the most common secondary reason for non-vaccination was religious taboos (31.4%). Majority of the respondents demonstrated poor knowledge of EPI schedules or VPDs. However, most believed that there was a need for more active government/NGO involvement in this area.

Conclusion

The most common primary reason for non-vaccination, i.e. lack of knowledge, and the most common secondary reason, i.e. religious taboos, imply that there is dire need to promote awareness among the masses in collaboration with NGOs, and major religious and social organizations.     

A phase I trial of oxaliplatin in combination with docetaxel in patients with advanced solid tumors

The primary objective of this trial was to establish the maximum tolerated dose (MTD) of oxaliplatin 130 mg/m² preceded by escalating doses of docetaxel 60 mg/m² (75, 90, 100 mg/m²) administered every 3 weeks. A total of 11 patients were entered; 10 evaluable for response: 4 stable disease (liver, ovary and esophagus) and 1 partial remission (esophagus). At dose level 1, there was 1 dose-limiting toxicity (DLT) (grade 3 allergic reaction). At dose level 2, there were 3 DLTs (3 grade 4 neutropenia, grade 3 gastritis, diarrhea, hypophosphatemia, neuro-mood). The MTD is docetaxel 60 mg/m² with oxaliplatin 130 mg/m².     

Comparison of apical transportation in four Ni-Ti rotary instrumentation techniques

A new radiographic technique was used to compare apical transportation in four Ni-Ti rotary instrumentation sequences. Mesiobuccal canals of 60 extracted mandibular molars were randomly divided into four groups. Groups 1 and 3 were instrumented by crown-down and groups 2 and 4 by step-back technique with 0.06 ProFiles series 29 to size 6. In groups 3 and 4 Greater Taper files were first used in a crown-down manner. The central axes of initial and final instruments were radiographically superimposed to measure loss of working length (WL) and transportation at 0, 0.5, 1, 3, and 5 mm from WL. ANOVA test showed no significant differences among groups regarding degree of transportation or loss of WL. Transportation was negatively correlated with radius of curvature at 0.5 and 5 mm from WL. The results indicate that the operational sequence of ProFiles or preinstrumentation with GT files has no effect on degree of transportation and loss of WL.     

The effectiveness of the Titan-S sonic scaler versus curettes in the removal of subgingival calculus. A human surgical evaluation

This study evaluated clinically the effectiveness of hand versus sonic subgingival scaling and root planing in the removal of calculus by visually examining the root surface at the time of periodontal flap surgery. Consideration was given to the method of instrumentation, probing depth, number of roots, and type of tooth surface. Eleven patients with moderate to advanced periodontal disease were evaluated. Four subjects were scaled and root planed with the Titan-S only, four with curettes only, and three with the Titan-S + curettes. At reevaluation 3 to 6 weeks after scaling and root planing, the decision to perform periodontal flap surgery was made based upon probing depth, bleeding upon probing, previous access to the root surface, furcation involvement, and the patient's level of oral hygiene. A full thickness mucoperiosteal flap was elevated to gain access to the root surface and measure the distance from the cementoenamel junction to the residual calculus. A total of 690 surfaces were evaluated surgically. The percentage of surfaces with residual calculus for each method of instrumentation was: Titan-S only (31.9%), curettes only (26.8%), and Titan-S + curettes (16.9%). Overall, 15.7% of the surfaces probing 0 to 3 mm, 29.3% of the surfaces probing 4 to 5 mm, and 44.4% of the surfaces probing 6 to 12 mm had residual calculus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trans-antral temporalis transfer for the repair of adult cleft palates

Temporalis muscle transfer is a versatile technique frequetly used for reconstructive procedures in the maxillofacial region. However the thickness of the pedicle may interfere with masticatory function when used anteriorly in the oral cavity. To repair full-length mid-palatal defects in fully dentate patients the flap can be passed through the maxillary sinus and combined with local repair of the soft palate, thus avoiding any occlusal trauma from the posterior teeth.
The operation is a single stage procedure with low morbidity and few complications, and is a useful technique for repairing the large untreated clefts frequently encountered in developing countries. The procedure is used by members of the Australian and New Zealand Association of Oral and Maxillofacial Surgeons Bangladesh Project who have operated in Dhaka teaching hospitals on a regular basis since 1991.     

Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory,apoptotic and growth mediators in experimental rats

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors.

Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.

Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters.

Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p?<?0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p?<?0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p?<?0.05) restored by NOF. Treatment produced a significant increase (p?<?0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p?<?0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p?<?0.05) by NOF. Histological alterations in wound skin were also restored by NOF.

Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.     

Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection

Purpose

To alleviate the harmful effects of radiations during occupational radiology, radiotherapy and diagnosis, radioprotective system with lower toxicity and extended activity is imperative. Trans-resveratrol (RVL) acts through free radical scavenging/antioxidant mechanism to mitigate the radiation-induced damage. But, its poor solubility and fast metabolism impede its efficacy. Thus, encapsulation of RVL into long circulating solid lipid nanoparticle (SLN) is aimed.

Method

Supercritical CO₂ solution of RVL, Gelucire®50/02 and Gelucire®50/13 SLN, was rapidly expanded into aqueous phase containing Tween 80, sonicated and lyophilized to get SLN. Particle size, polydispersity index (PDI), entrapment efficiency (%EE), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), drug release, in vivo pharmacokinetics, antioxidant assays, radiation-induced lipid peroxidation and plasmid DNA relaxation assays were studied. Stability studies were performed to analyze drug degradation and shelf life.

Results

Optimized formulation (F9) had %yield, particle size, PDI, %EE and %drug release (after 72 h) of 68.48?±?5.73 %, 276.7?±?5.33 nm, 0.18?±?0.032, 62.66?±?4.52 % and 70.05?±?3.003 %, respectively. Electron microscopy revealed nearly spherical particles, while DSC and XRD showed reduced crystalline peaks. F9 showed higher AUC and sustained release of RVL in rats (i.v. bolus) and increased antioxidant activities and radioprotection as compared to RVL solution. Shelf life of >2 years was predicted for F9 (at 8 °C).

Conclusion

Results are encouraging to use F9 for radiation exposure prophylaxis.