Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats

OBJECTIVE: Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria. This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats.METHODS: Thirty male rats were separated into 6 groups(A–F) of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle(distilled water), cimetidine 200 mg/kg body weight(BW), or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW(groups A, B, C, D, E and F, respectively). Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation. RESULTS: Carica papaya seed extract significantly(P<0.05) increased gastric p H and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly(P<0.05) decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups(D, E and F) were increased significantly over the group B(P<0.05). Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract. CONCLUSION: In this study, pretreatment with aqueous extract of Carica papaya seed exhibited antiulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.     

Spatial mapping of proteoglycan content in articular cartilage using near-infrared (NIR) spectroscopy

Diagnosis of articular cartilage pathology in the early disease stages using current clinical diagnostic imaging modalities is challenging, particularly because there is often no visible change in the tissue surface and matrix content, such as proteoglycans (PG). In this study, we propose the use of near infrared (NIR) spectroscopy to spatially map PG content in articular cartilage. The relationship between NIR spectra and reference data (PG content) obtained from histology of normal and artificially induced PG-depleted cartilage samples was investigated using principal component (PC) and partial least squares (PLS) regression analyses. Significant correlation was obtained between both data (R² = 91.40%, p<0.0001). The resulting correlation was used to predict PG content from spectra acquired from whole joint sample, this was then employed to spatially map this component of cartilage across the intact sample. We conclude that NIR spectroscopy is a feasible tool for evaluating cartilage contents and mapping their distribution across mammalian joint.OCIS codes: (170.6510) Spectroscopy, tissue diagnostics; (170.6935) Tissue characterization; (170.3880) Medical and biological imaging     

Psychiatric morbidity in stroke patients attending a neurology clinic in Nigeria

Back ground

Stroke produces a wide range of mental and emotional disorders. Neuropsychiatric complications associated with stroke may have negative effects on the social functioning, overall quality of life and the recovery of motor functioning of stroke survivors.

Objective

To determine the prevalence and nature of psychiatric morbidity among stroke patients attending neurology outpatient clinic of the University of Ilorin Teaching Hospital (UITH), Ilorin-Nigeria.

Methods

All patients with stroke aged 18 years and above at an outpatient neurology clinic in Ilorin, Nigeria were assessed for mental and emotional disorders using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) over one year (March 2009 to February 2010).

Results

Overall prevalence of psychiatric morbidity was 36.0% (30/83) among 83 patients who constituted the study population. Specific diagnoses recorded were depression (19.2%), generalised anxiety disorder (9.6%), harmful alcohol use (2.4%); dementia, somatoform disorder, phobia and delusional disorder each had a prevalence of 1.2%. Clinical and sociodemographic variables were not significantly associated with psychiatric morbidity.

Conclusion

Psychiatric disorders are often associated with stroke. Identifying and treating stroke patients with these psychiatric co-morbidities could thus help to improve the overall quality of life of these patients.     

A novel approach to the development of benchmarking parameters for characterizing cartilage health

This article outlines the motivation and preliminary investigations into a novel method of characterizing cartilage health for potential in vivo application. Current in vivo indentation techniques, which primarily rely on stiffness measurements based on axial data, are unable to adequately distinguish between healthy and degraded tissue. The present in vitro study investigates the effects of controlled artificial degradation on the effective surface stretch, comparing the results with those obtained from the peripheral cartilage surrounding focal osteoarthritis. Results suggest that this technique is highly sensitive, showing a maximum range of 14% effective surface stretch in a normal joint compared with 42% for axial strain measurements. We further demonstrated that the technique can discriminate between degenerative changes and the intrinsic variations in cartilage properties across the normal joint. From these investigations we propose that the relationship between indentation and the in-plane strain field under the indenter can better distinguish degraded tissue than the currently used stiffness techniques.     

Conceptual fracture parameters for articular cartilage

BACKGROUND: Superficial cracks can occur in articular cartilage due to trauma or wear and tear. Our understanding of the behaviour of such cracks in a loaded matrix is limited. A notable study investigated the growth of cracks induced in the bottom layer of the matrix. This paper extends existing studies, characterizing the propagation of superficial cracks and matrix resistance under tension at varying rates of loading. METHODS: Cartilage strips with artificially induced superficial cracks were subjected to tensile loading at different loading velocities using a miniature tensile testing device. Load-displacement data, video and still images were recorded for analysis. FINDINGS: The propagation of superficial cracks in articular cartilage does not follow the classical crack tip advance that is characteristic of most engineering materials. Instead, the crack tip exhibited a negligible movement while the side edges of the crack rotated about it, accompanied by matrix stretching and an upward pull (necking) of the bottom layer of the sample. As loading progresses, the crack edges stretch and rotate to assume a position parallel to the articular surface, followed by the final fracture of the matrix at a point just below the crack tip. Using the recorded mechanical data and images, an analogous poroelastic fracture toughness, Kp(Ic)=1.83 MPa.square root mm (SD 0.8) is introduced. INTERPRETATION: It is extremely difficult for a superficial crack to propagate through articular cartilage. This may be because of the energy dissipation from the crack due to the movement and exudation of water, and large stretching of the matrix.