Progressive and regressive changes in the nucleus pulposus. Part I. The neonate

Magnetic resonance (MR) imaging, correlated with anatomic sections, was used to characterize the progressive and regressive changes in the nucleus pulposus in neonates. The spines of five fetuses and five full-term infants between 16 and 40 weeks old were studied. In anatomic sections, the nucleus pulposus was sharply demarcated from the anulus fibrosus, Sharpey fibers were conspicuous, and a plate of primitive notochord was evident in the equator of the disk. On long repetition time (TR)/long echo time (TE) or long TR/short TE MR images, Sharpey fibers (low signal intensity) and notochord (low signal intensity) could be differentiated from the high-signal-intensity nucleus pulposus and anulus fibrosus. The major differences between the fetal and infant spines were the amount of notochord in the disk and ossification in the vertebral body.     

Titanium elastic nailing in femoral diaphyseal fractures of children in 6-16 years of age

Background:

Management of femoral diaphyseal fractures in the age group of 6-16 years is controversial. There has been a resurgence worldwide for operative fixation.

Materials and Methods:

Twenty-two children (18 boys, 4 girls) aged 6-16 years with recent (> 3 days) femoral diaphyseal fractures (20 closed, 2 open) were stabilized with Titanium Elastic Nail (TEN). These fractures were in proximal third (n=3), middle third (n=15) and in the distal third (n=4) 17 patients underwent surgery within seven days of their injury. The results were evaluated using Flynn''s scoring criteria. Statistical analysis was done using Fischer''s exact test.

Results:

All 22 patients were available for evaluation after a mean of 26 months (14-36 months) of followup. Radiological union in all cases were achieved in a mean time of 8.7 weeks. Full weight bearing was possible in a mean time of 8.8 weeks. Mean duration of hospital stay was 9.8 days. The results were excellent in 13 patients (59.0%), successful in six (27.2%) and poor in three patients (13.6%). All patients had early return to school.

Conclusion:

Intramedullary fixation titanium elastic nailing is an effective treatment of diaphyseal fractures of the femur in properly selected patients of the 6-16 years age group.     

Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase

Background and purpose:

Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.

Experimental approach:

Cell-based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).

Key results:

Thalidomide inhibited pro-angiogenic functions in endothelial cell cultures, whereas 8-bromo-cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8-bromo-cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration-dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO-dependent angiogenesis.

Conclusion and implications:

Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti-angiogenic effects. These results could lead to the formulation of thalidomide-based drugs to curb angiogenesis by targeting sGC.     

Anterior compartment pressure measurement in closed fractures of leg

Background:

Compartment syndrome is a potentially devastating condition. Increased intracompartmental pressure has been incriminated as the primary pathogenic factor in compartment syndrome. The purpose of this prospective study was to monitor the anterior compartmental pressure and differential pressure to minimize the incidence of acute compartment syndrome.

Materials and Methods:

Seventy-five consecutive cases of closed fractures of leg presenting within six hours of injury were taken for measurement of anterior compartment pressure at the level of fracture and at 5 cm and 10 cm away from the fracture site, using the Whitesides'' infusion technique. A differential pressure of less than 30 mm Hg was taken as the criterion for diagnosis of compartment syndrome.

Results:

Two patients (2.67%) developed acute compartment syndrome. The mean anterior compartment pressures were highest at the level of the fracture and went on decreasing as we went away from the fracture site, which was found to be statistically significant (P < 0.001).

Conclusion:

Compartment pressure measurement is the most reliable and objective method for early diagnosis of compartment syndrome. Whitesides'' infusion technique is a relatively easy and inexpensive method to come to a diagnosis of compartment syndrome in a developing country like India. Differential pressure is more reliable than absolute pressure in predicting the development of an impending compartment syndrome.     

RNAi knock-down of the Litopenaeus vannamei Toll gene (LvToll) significantly increases mortality and reduces bacterial clearance after challenge with Vibrio harveyi

In this study, we used real-time PCR to simultaneously monitor the responses of 12 key genes of the shrimp innate immune system in Litopenaeus vannamei after challenge with Vibrio harveyi. In the proPO activating system, we found that proPO was up-regulated (3.3× control at 36 hpi). The hemolymph clotting genes transglutaminase (TGase) and clotting protein were also up-regulated, as were 5 genes in the antimicrobial peptide system (ALF, Crustin, Lyz, PEN2 and PEN4), with only PEN3 showing no significant changes. In the antioxidant defense system, SOD was slightly elevated while GPx was substantially down-regulated. In the pattern recognition receptor system, at 24 hpi, the Toll gene (LvToll) showed the highest relative increase in expression level of all the investigated genes (15× greater than the sterile seawater control). In the second part of this study, when LvToll was knocked down by RNAi silencing, there was no effect on either survival rates or bacterial number in unchallenged shrimp. There was also no difference in mortality rates between control shrimp and LvToll-silenced shrimp when these two groups were challenged with a viral pathogen (white spot syndrome virus; WSSV). However, when LvToll-silenced shrimp were challenged by V. harveyi, there was a significant increase in mortality and bacterial CFU counts. We note that the increase in bacterial CFU count occurred even though treatment with EGFP dsRNA had the opposite effect of reducing the CFU counts. We conclude that LvToll is an important factor in the shrimp innate immune response to acute V. harveyi infection, but not to WSSV.