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.     

Isolated foveal hypoplasia with secondary nystagmus and low vision is associated with a homozygous SLC38A8 mutation

Foveal hypoplasia, always accompanied by nystagmus, is found as part of the clinical spectrum of various eye disorders such as aniridia, albinism and achromatopsia. However, the molecular basis of isolated autosomal recessive foveal hypoplasia is yet unknown. Individuals of apparently unrelated non consanguineous Israeli families of Jewish Indian (Mumbai) ancestry presented with isolated foveal hypoplasia associated with congenital nystagmus and reduced visual acuity. Genome-wide homozygosity mapping followed by fine mapping defined a 830 Kb disease-associated locus (LOD score 3.5). Whole-exome sequencing identified a single missense mutation in the homozygosity region: c.95T>G, p.(Ile32Ser), in a conserved amino acid within the first predicted transmembrane domain of SLC38A8. The mutation fully segregated with the disease-associated phenotype, demonstrating an ∼10% carrier rate in Mumbai Jews. SLC38A8 encodes a putative sodium-dependent amino-acid/proton antiporter, which we showed to be expressed solely in the eye. Thus, a homozygous SLC38A8 mutation likely underlies isolated foveal hypoplasia.     

Finite element analysis of different surgical approaches in various occlusal loading locations for zygomatic implant placement for the treatment of atrophic maxillae

The aim of this study was to compare two different types of surgical approaches, intrasinus and extramaxillary, for the placement of zygomatic implants to treat atrophic maxillae. A computational finite element simulation was used to analyze the strength of implant anchorage for both approaches in various occlusal loading locations. Three-dimensional models of the craniofacial structures surrounding a region of interest, soft tissue and framework were developed using computed tomography image datasets. The implants were modelled using computer-aided design software. The bone was assumed to be linear isotropic with a stiffness of 13.4GPa, and the implants were assumed to be made of titanium with a stiffness of 110GPa. Masseter forces of 300N were applied at the zygomatic arch, and occlusal loads of 150N were applied vertically onto the framework surface at different locations. The intrasinus approach demonstrated more satisfactory results and could be a viable treatment option. The extramaxillary approach could also be recommended as a reasonable treatment option, provided some improvements are made to address the cantilever effects seen with that approach.     

Serum prolidase activity,oxidative stress,and nitric oxide levels in patients with bladder cancer

Objectives

Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity.

Design and methods

Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined.

Results

Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05).

Conclusions

Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.

     

Degree of abnormality is associated with rate of change in measures of beta-amyloid,glucose metabolism and cognition in an autopsy-verified Alzheimer’s disease case

The degree of abnormality and rate of change in cognitive functions, positron emission tomography Pittsburg compound B (PET PIB), and fluorodeoxyglucose (FDG) measures were studied for 8 years in an autopsy-confirmed Alzheimer’s disease (AD) patient, who died 61 years old (Mini-Mental State Examination (MMSE) score 7). At first encounter with medical care, the patient was very mildly demented (MMSE score 27). She had four cognitive assessments and two examinations with PET PIB and FDG in 23 bilateral brain regions. The onset of cognitive decline was retrospectively estimated to have started in the early forties. The degree of impairment was inversely related to the rate of decline. A similar relationship was seen between the rate of change and the level of abnormality in both PIB and FDG. To conclude, rate of change in cognition, PIB, and FDG was associated with the degree of abnormality.     

The outcome of endometrial ablation in women with inherited bleeding disorders

There are currently limited data on the use of endometrial ablation in the treatment of heavy menstrual bleeding (HMB) in women with inherited bleeding disorders (IBDs). A retrospective review of prospectively collected data was performed. Twelve women with IBDs who had received endometrial ablation for the treatment of HMB were identified and their records reviewed. Details of their menstrual history; quality of life (QOL) and amount of menstrual blood loss [as assessed by pictorial blood-loss assessment chart (PBAC) and haemoglobin (Hb) concentration] pre and post-ablation were collected. Twelve women were included. The median duration of follow-up post-ablation was 32 months (range, 6-76). The median duration of menstruation decreased from 11 to 0 days after treatment (P = 0.004). Median PBAC scores decreased from 1208 preop to 0 post-ablation (P = 0.002).The median Hb concentrations (10.5-13.1 g dL(-1)) and QOL scores (median, 17-54) improved significantly after endometrial ablation (P < 0.01). Endometrial ablation appears to be a safe and effective long-term treatment for HMB in women with IDBs. It significantly decreases menstrual blood loss and improves QOL.