The association between HLA genes and radiological erosions in Malaysian patients with rheumatoid arthritis

Objective: To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).

Methods: In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP)—PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen–Dale method. Demographic data and treatment given to the patients were obtained from their case records.

Results: Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.

Conclusions: In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.     

Population data and genetic characteristics of 12 X-STR loci using the Investigator® Argus X-12 Quality Sensor kit for the Kedayan population of Borneo in Malaysia

International Journal of Legal Medicine - DNA profiling of X-chromosomal short tandem repeats (X-STR) has exceptional value in criminal investigations, especially for complex kinship and incest...     

Longevity of complete dentures: A systematic review and meta-analysis

Statement of problemPatients and clinicians are aware of the efficacy and benefits of complete dentures, but evidence regarding their longevity is limited.PurposeThe purpose of this systematic review was to examine the literature describing the longevity of complete dentures and to review variations in longevity by denture type and duration of follow-up.Material and methodsFour electronic databases were searched by using key terms: MEDLINE, CINAHL (EBSCO), Dentistry and Oral Sciences Databases, and The Cochrane Library. Studies meeting the inclusion criteria were reviewed according to an established protocol and data extracted. Reference lists of identified studies were examined. Risk of bias was assessed by using the AXIS tool. Weighted means and weighted standard deviations were calculated. Pooled complete denture failure proportions were estimated by using random effects models based on the DerSimonian and Laird method.ResultsThe search yielded 21 607 unique abstracts, of which 273 met the inclusion criteria. Assessment of the full-text articles reduced this number to 42. Of these, 24 studies were rated as having low risk of bias and 18 as very low. The weighted mean ±standard deviation longevity of maxillary complete dentures was 10.3 ±3.8 years, of mandibular dentures was 8.6 ±2.6 years, and of both maxillary and mandibular dentures was 10.8 ±4.7 years. The pooled failure proportion for complete dentures observed for 2 years or less was 0.05 (95% confidence interval [CI]: 0.00-0.10), 5 to 6 years was 0.12 (95% CI: 0.08-0.16), and 10 years or more was 0.41 (95% CI: 0.28-0.53).ConclusionsComplete dentures, fabricated primarily in university settings, were found to have a weighted mean ±standard deviation longevity of 10.1 ±4.0 years. The failure rate of these prostheses increased with denture age, and the longevity of maxillary dentures was greater than that of mandibular dentures.     

Chikungunya infection in Malaysia: Comparison with dengue infection in adults and predictors of persistent arthralgia

BackgroundChikungunya virus (CHIKV) and dengue virus (DENV) co-circulate in areas endemic with the Aedes mosquito vectors. Both viruses cause similar illnesses which may be difficult to distinguish clinically. CHIKV is also associated with persistent arthralgia.ObjectivesTo compare and describe factors which differentiate between DENV and CHIKV infections on presentation; and to describe predictors of persistent arthralgia in CHIKV patients.Study designPatients aged >14 years diagnosed with acute CHIKV and DENV infections in Kuala Lumpur, Malaysia were retrospectively identified. Clinical and laboratory data were obtained from medical records, and compared. CHIKV patients were telephoned 15–24 months later and interviewed about persistent symptoms. Logistic regression analysis was performed.ResultsA total of 53 CHIKV and 113 DENV patients were included. CHIKV patients were older and more likely to be female. CHIKV was independently associated with arthralgia and rash, while DENV was associated with myalgia, raised aspartate transaminase, and leucopaenia. Forty CHIKV patients were followed up, with a median duration of self-reported arthralgia of 3 months (range, 0–24 months). Eighteen (45%) had persistent arthralgia beyond 4 months, for which age >40 years was an independent predictor. At 1 year, 9 (22.5%) patients had arthralgia.ConclusionIn Kuala Lumpur, selected clinical and laboratory predictors help to distinguish between DENV and CHIKV infections. Persistent arthralgia was a frequent sequel of CHIKV infection in this cohort.     

Isoflavone Genistein Induces Fluid Secretion and Morphological Changes in the Uteri of Post-Pubertal Rats

A reported increase in the incidence of infertility following high genistein intake could be related to alteration in the normal fluid volume and morphology of the uterus in adult female. In view of this, we investigated the effect of this compound on fluid secretion, fluid volume and morphology of the uterus in post-pubertal rats. Methods: Ovariectomised SD rats were treated with 17-β oestradiol (E) (0.8 X 10^-4 mg/kg/day) and genistein (0.5, 5, 10, 25, 50 and 100 mg/kg/day) for three days. Following drug treatment, in-vivo uterine perfusion was performed and the rate of fluid secretion and the volume of fluid in the uterus were determined via changes in weight (μl/min) and F-dextran concentration of the perfusate respectively. The animals were then sacrificed and the uteri were removed for weight determination, morphological analyses and proliferative cell nuclear antigen (PCNA) expression analyses by Western blotting. Results: Subcutaneous genistein treatment resulted in a dose-dependent increase in fluid secretion rate, fluid volume and uterine wet weight. Treatment with 100 mg/kg/day genistein resulted in a remarkable increase in the rate of uterine fluid secretion, the volume of the uterine luminal fluid as well as the circumference of the uterine and uterine glandular lumen suggesting an excessive fluid accumulation. Meanwhile, there were evidence of glandular hyperplasia and an increase in the expression of PCNA following treatment with 50 and 100 mg/kg/day genistein. Conclusion: High genistein intake could potentially cause adverse effects on the uterus by inducing excessive fluid secretion and accumulation as well as hyperplasia.     

Evaluation of the humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> of mice immunized with liposomes containing glycolipids of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

Mycobacterium smegmati s (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.     

Evaluation of specific humoral immune response and cross reactivity against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigens induced in mice immunized with liposomes composed of total lipids extracted from <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.     

In Silico identification of M. TB proteins with diagnostic potential

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.

     

New amino group functionalized porous carbon for strong chelation ability towards toxic heavy metals

Herein, ethylenediamine functionalized porous carbon (PC-ED/1.5) was synthesized, then characterized by various methods and finally used as a functional material for Cu(ii) and Pb(ii) ion removal from water. XPS revealed the presence of numerous functionalities within the surface of PC including –NH and C–N–C groups. Furthermore, S_BET, RS, XRD and FTIR analyses confirmed the changes implemented on the PC surface. Thereafter, a systematic study was implemented to analyze the interactions of the PC-ED/1.5 surface with Cu(ii) and Pb(ii) heavy metal ions. Hence, adsorption experiments showed that the PC-ED/1.5 exhibits maximum adsorption capacities of 123.45 mg g⁻¹ and 140.84 mg g⁻¹ for Cu(ii) and Pb(ii), respectively. Moreover, in situ electrostatic interactions occurring between the divalent cation and the PC-ED/1.5 functional groups was investigated. The mechanism involves chelation processes, electrostatic interactions and mechanical trapping of the metal ions in the adsorbent pores. Interestingly, a synergistic effect of the pores and surface active sites was observed. Finally, by using alginate bio-polymer we prepared membrane films of PC-ED/1.5 which showed long-term stability, regeneration capabilities and high mass recovery.

Herein, ethylenediamine functionalized porous carbon (PC-ED/1.5) was synthesized, then characterized by various methods and finally used as a functional material for Cu(ii) and Pb(ii) ion removal from water.