Melastatin-related transient receptor potential 2 channel in Aβ_(42)-induced neuroinflammation: implications to Alzheimer's disease mechanism and development of therapeutics

正Alzheimer’s disease(AD)is an age-related neurodegenerative disease that represents the most common cause of dementia among the elderly people.With the increasingly aging population,AD has presented an overwhelming healthcare challenge to modern society;the World Alzheimer Report 2015 has estimated that 46.8 million people worldwide lived with dementia in 2015 and this number will rise to74.7 million in 2030 and that the total cost of dementia was 818 billion in US$in 2015 and will reach two trillion in 2030.Post-mortem     

Huge adrenal haemangioma

Adrenal tumours are either functioning or non-functioning. Non-functioning adrenal tumours are generally asymptomatic and usually of enormous proportions at the time of presentation. A case is presented here of a patient with a huge right adrenal haemangioma which was successfully treated surgically. This unusual tumour was 25 cm in diameter, was well encapsulated and weighed 4 kg. The literature pertaining to this interesting case is reviewed.     

Comparison of bioengineered human bone construct from four sources of osteogenic cells

Osteoprogenitor cells have been reported to be present in periosteum, cancellous and cortical bone, and bone marrow; but no attempt to identify the best cell source for bone tissue engineering has yet been reported. In this study, we aimed to investigate the growth and differentiation pattern of cells derived from these four sources in terms of cell doubling time and expression of osteoblast-specific markers in both monolayer cells and three-dimensional cell constructs in vitro. In parallel, human plasma derived-fibrin was evaluated for use as biomaterial when forming three-dimensional bone constructs. Our findings showed osteoprogenitor cells derived from periosteum to be most proliferative followed by cortical bone, cancellous bone, and then bone marrow aspirate. Bone-forming activity was observed in constructs formed with cells derived from periosteum, whereas calcium deposition was seen throughout the constructs formed with cells derived from cancellous and cortical bones. Although no mineralization activity was seen in constructs formed with osteoprogenitor cells derived from bone marrow, well-organized lacunae as would appear in the early phase of bone reconstruction were noted. Scanning electron microscopy evaluation showed cell proliferation throughout the fibrin matrix, suggesting the possible application of human fibrin as the bioengineered tissue scaffold at non-load-bearing sites.     

The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats

Background

The third trimester in human fetal development represents a critical time of brain maturation referred to as the “brain growth spurt”. This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats.

Methods

On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning.

Results

Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure.

Conclusion

These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat.     

HPV infection and the alterations of the pRB pathway in oral carcinogenesis

Inactivation of the retinoblastoma (pRB) pathway is a common event in oral squamous cell carcinoma particularly through the aberrant expression of the components within this pathway. This study examines the alterations of molecules within the pRB pathway by looking at the presence of homozygous deletions in p16(INK4A) and the expression patterns of pRB, cyclin D1 and CDK4, as well as the presence of human papillomavirus (HPV) in our samples. In our study, 5/20 samples demonstrated deletions of p16(INK4A) exon 1alpha. pRB overexpression was found in 20/20 samples, the expression was mainly observed in all layers of the epithelia, particularly in the basal layer where cells are actively dividing and aberrant pRB expression was found in 12/20 samples. Cyclin D1 and CDK4 overexpression was detected in 6/20 and 2/20 samples respectively in comparison to hyperplasias where both proteins were either not expressed or expressed at minimal levels (<10%). Strikingly, HPV was found to be present in all of our samples, suggesting that HPV plays a significant role in driving oral carcinogenesis. Notably, 17/20 of our samples showed more than one alteration in the pRB pathway, however, we did not find any significant relationship between the presence of HPV, homozygous deletion of p16(INK4A) and overexpression of pRB, cyclin D1 and CDK4. Collectively, this data demonstrates that alterations in the pRB pathway are a common event and involve the aberration of more than one molecule within the pathway. Furthermore, the involvement of HPV in all our samples suggests that HPV infection may play an important role in oral carcinogenesis.     

Facial Fractures in Kajang Hospital,Malaysia: A 5-Year Review

Abstract Objective: The objective of this study was to determine the demographic data as well as other relevant data pertaining to the management of patients with maxillofacial injury in a Malaysian government regional hospital. Study Design: Medical records of 313 patients who sustained maxillofacial injury treated in Kajang Hospital, Selangor, Malaysia over a 5-year period (1998–2002) were collected. Data regarding age, gender and race, etiology of injury, site of injury, other associated injuries and treatment undertaken were analyzed. Results: Two hundred and forty-nine male (79.6%) and 64 female patients (20.4%) were treated for maxillofacial trauma. The patients' age range from 1 to 67 years old, with a median age of 23 years old. A high number of Malays (60.1%) sustained maxillofacial injury, followed by Indians (16%), Chinese (13.4%) and other races (10.5%). Road traffic accident was the main etiology for maxillofacial injury with 230 cases (73.5%), followed by fall (16.6%), assault (5.4%), industrial accident (2.6%), sports injuries (0.6%) and others (1.3%). Mandibular fractures were the most common, occurring in 83.1% of the cases while the midfacial fractures accounted for 16.9%. Majority of patients were treated with closed reduction and intermaxillary fixation (88.1%) and 11.9% underwent open reduction and internal fixation. Conclusion: Road traffic accident involving motorcyclists was the main cause of maxillofacial trauma in Malaysia. The most common facial fracture was the mandibular fracture. Non-surgical manipulation of fracture was the most common treatment carried out in this hospital.     

Establishment and characterization of Asian oral cancer cell lines as in vitro models to study a disease prevalent in Asia

We have established 3 cell lines ORL-48, -115 and -136 from surgically resected specimens obtained from untreated primary human oral squamous cell carcinomas of the oral cavity. The in vitro growth characteristics, epithelial origin, in vitro anchorage independency, human papilloma-virus (HPV) infection, microsatellite instability status, karyotype and the status of various cell cycle regulators and gatekeepers of these cell lines were investigated. All 3 cell lines grew as monolayers with doubling times ranging between 26.4 and 40.8 h and were immortal. Karyotyping confirmed that these cell lines were of human origin with multiple random losses and gains of entire chromosomes and regions of chromosomes. Immunohistochemistry staining of cytokeratins confirmed the epithelial origin of these cell lines, and the low degree of anchorage independency expressed by these cell lines suggests non-transformed phenotypes. Genetic analysis identified mutations in the p53 gene in all cell lines and hypermethylation of p16INK4a in ORL-48 and -136. Analysis of MDM2 and EGFR expression indicated MDM2 overexpression in ORL-48 and EGFR overexpression in ORL-136 in comparison to the protein levels in normal oral keratinocytes. Analysis of the BAT-26 polyadenine repeat sequence and MLH-1 and MSH-2 repair enzymes demonstrated that all 3 cell lines were microsatellite stable. The role of HPV in driving carcinogenesis in these tumours was negated by the absence of HPV. Finally, analysis of the tissues from which these cell lines were derived indicated that the cell lines were genetically representative of the tumours, and, therefore, are useful tools in the understanding of the molecular changes associated with oral cancers.     

Concentrations of Cadmium,Copper, and Zinc in <Emphasis Type="Italic">Macrobrachium rosenbergii</Emphasis> (Giant Freshwater Prawn) from Natural Environment

This study analyzed the levels of cadmium (Cd), copper (Cu), and zinc (Zn) by the flame atomic absorption spectrophotometer (FAAS), in the muscle tissues, exoskeletons, and gills from freshwater prawn (Macrobrachium rosenbergii) (n?=?20) harvested from natural habitat in Kerang River, Malaysia on 25th November 2015. Significant increase of the metals level in muscle tissue and gill (r?>?0.70, p?<?0.05) were observed with increase in length except for Cu in gills. No relationship was found between metals level in exoskeleton and length. The concentrations of Cd, Cu and Zn were significantly higher (p?<?0.05) in males (muscle tissues and exoskeleton) except for Cd in exoskeleton. In gills, only Cu was significantly higher (p?<?0.05) in female than male. All samples contained metals below the permissible limit for human consumption (i.e., Cd?<?2.00 mg/kg; Cu?<?30.00 mg/kg; Zn?<?150 mg/kg). Annual metals monitoring in prawn and environmental samples is recommended to evaluate changes of metals bioaccumulation and cycling in the system, which is useful for resources management.     

Correlation between free thyroxin levels and left ventricular ejection fraction in Graves' disease (preliminary study)

AIM: to determine the correlation between free thyroid hormone level and left ventricular ejection fraction in newly diagnosed Graves' patients. METHODS: this is a preliminary study with an initial cross-sectional design using free thyroxine level as a parameter of thyroid hormone state and left ventricular ejection fraction (LVEF) as a parameter of left ventricular systolic function. Free thyroxine level was measured in the laboratory and the LVEF was assessed by Simpson's methods of echocardiography study. RESULTS: ten patients (7 men and 3 women; age 18-52 years old) were studied. Their average of fT4 was 5.75 (SD 0.96) ng/dL and their average of LVEF was 70.57 (SD 4.50)%. There was positive correlation coefficient between free thyroxine level and left ventricular ejection fraction (r=0.711, p=0.021) in newly diagnosed Graves' patients. CONCLUSION: in this study strong positive correlation was found between free thyroxine (fT4) and left ventricular ejection fraction (LVEF) in newly diagnosed Graves' patients.