Intraoperative ultrasound examination of the brain

In a preliminary demonstration of cranial intraoperative real-time ultrasound, both supratentorial and posterior fossa scans displayed the pertinent anatomy. A grade III astrocytoma was visualized on the supratentorial scan as well. Ultrasound may be valuable for surgical planning and biopsy procedures because of its reliable depiction of intracranial anatomy and ease of use.     

Perforin is a critical physiologic regulator of T-cell activation

Individuals with impaired perforin-dependent cytotoxic function (Ctx(-)) develop a fatal inflammatory disorder called hemophagocytic lymphohistiocytosis (HLH). It has been hypothesized that immune hyperactivation during HLH is caused by heightened infection, defective apoptosis/responsiveness of Ctx(-) lymphocytes, or enhanced antigen presentation. Whereas clinical and experimental data suggest that increased T-cell activation drives HLH, potential abnormalities of T-cell activation have not been well characterized in Ctx(-) hosts. To define such abnormalities and to test these hypotheses, we assessed in vivo T-cell activation kinetics and viral loads after lymphocytic choriomeningitis virus (LCMV) infection of Ctx(-) mice. We found that increased T-cell activation occurred early during infection of Ctx(-) mice, while they had viral burdens that were identical to those of WT animals, demonstrating that T-cell hyperactivation was independent of viral load. Furthermore, cell transfer and signaling studies indicated that increased antigenic stimulation, not a cell-intrinsic defect of responsiveness, underlay heightened T-cell activation in vivo. Finally, direct measurement of viral antigen presentation demonstrated an increase in Ctx(-) mice that was proportional to abnormal T-cell activation. We conclude that perforin-dependent cytotoxicity has an immunoregulatory role that is distinguishable from its pathogen clearance function and limits T-cell activation in the physiologic context by suppressing antigen presentation.     

Identification and synthesis of novel inhibitors of acetyl-CoA carboxylase with in vitro and in vivo efficacy on fat oxidation

Acetyl CoA carboxylase isoforms 1 and 2 (ACC1/2) are key enzymes of fat utilization and their inhibition is considered to improve aspects of the metabolic syndrome. To identify pharmacological inhibitors of ACC1/2, a high throughput screen was performed which resulted in the identification of the lead compound 3 ( Gargazanli , G. ; Lardenois , P. ; Frost , J. ; George , P. Patent WO9855474 A1, 1998 ) as a moderate selective ACC2 inhibitor. Optimization of 3 led to 4m ( Zoller , G. ; Schmoll , D. ; Mueller , M. ; Haschke , G. ; Focken , I. Patent WO2010003624 A2, 2010 ) as a submicromolar dual ACC1/2 inhibitor of the rat and human isoforms. 4m possessed favorable pharmacokinetic parameters. This compound stimulated fat oxidation in vivo and reduced plasma triglyceride levels in a rodent model after subchronic administration. 4m is a suitable tool compound for the elucidation of the pharmacological potential of ACC1/2 inhibition.     

Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1alpha

Constitutive expression of cell-associated, but not secreted, interleukin-1alpha (IL-1alpha) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1alpha-expressing tumor cells induce progressive tumors in mice. In vivo and ex vivo experiments have shown that regression of IL-1alpha-positive fibrosarcoma cells depends on CD8(+) T cells, which can also be activated in CD4(+) T cell-depleted mice, with some contribution of natural killer cells. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, some early and transient manifestations of antitumor-specific immunity, such as activation of specific proliferating T cells, are evident; however, no development of cytolytic T lymphocytes or other antitumor protective cells could be detected. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, the development of early tumor-mediated suppression was observed, and in spleens of mice injected with IL-1alpha-positive fibrosarcoma cells, protective immunity developed in parallel to tumor regression. Treatment of mice bearing violent fibrosarcoma tumors with syngeneic-inactivated, IL-1alpha-positive fibrosarcoma cells, at a critical interval after injection of the malignant cells (Days 5-12), induced tumor regression, possibly by potentiating and amplifying transient antitumor cell immune responses or by ablation of tumor-mediated suppression. Membrane-associated IL-1alpha may thus serve as an adhesion molecule, which allows efficient cell-to-cell interactions between the malignant and immune effector cells that bear IL-1Rs and function as a focused cytokine with adjuvant activities at nontoxic, low levels of expression. Our results also point to the potential of using antitumor immunotherapeutic approaches using cell-associated IL-1alpha.     

Q-angle, Pelvic width, and Intercondylar notch width as predictors of knee injuries in women soccer players in South Africa

Objective

To investigate the association between the three anatomical factors of Q-angle (QA), pelvic width (PW) and Intercondylar notch width (INW) and knee injuries among the U-23 female soccer players of South Africa

Methods

The study is a case-control prospective study design. Twenty four U-23 women soccer players of the South African team were purposively chosen to participate in this study. Participants were divided into two groups: group1 (Case) was those with knee injuries, while those without injuries were in group-2 (Control). PW and INW were measured after X-rays of the hip were taken while the QA was measured manually with the goniomenter. Association between anatomical factors and knee injuries were tested with ANOVA.

Results

Q-angle ranged from 14° to 18° for both injured and non injured groups. PW was between 24 –29 cm for both injured and non injured groups. INW was between 1.3mm and 2.8mm for the right and between 1.4mm and 2.5mm for the left notch for the injured group, while INW for the right and left of the non injured group were between 1.7mm to 2.1mm and 1.8mm to 2.1mm, respectively No significant association between knee injuries and each of the anatomical factors was found QA (p= 0.74), PW (p=0.34), INW (right and left respectively) (p=0.142 & p=0.089).

Conclusion

The three anatomical factors of QA, PW and INW could not be used to predict knee injuries amongst the U-23 female players in South Africa.