Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome

Background

Idiopathic steroid-resistant nephrotic syndrome (SRNS) has been associated with the presence of a circulating focal sclerosis permeability factor (FSPF) thought to damage the glomerular barrier and increase permeability to albumin. Galactose binds and inactivates FSPF in vitro, but its effect in vivo is uncertain.

Methods

A prospective clinical trial was conducted to investigate the effect of oral galactose on FSPF and proteinuria in children with SRNS. Seven pediatric subjects with idiopathic SRNS and positive FSPF activity (>0.5) were treated with oral galactose (0.2 gm/kg/dose twice daily) for 16 weeks. Post-treatment FSPF and proteinuria were measured.

Results

Focal sclerosis permeability factor activity of the seven subjects decreased from 0.69?±?0.11 to 0.35?±?0.21 (p?=?0.009) in response to galactose. The two subjects with post-transplant recurrence of focal segmental glomerulosclerosis (FSGS) demonstrated the most significant improvement in FSPF (p?=?0.006). Despite this decrease in FSPF, the pre- and post-treatment urine protein:creatinine ratio remained unchanged and no subject achieved remission.

Conclusions

Galactose decreases FSPF in children with SRNS, with the most significant improvement in those with post-transplant FSGS recurrence, but it fails to improve proteinuria. At the present time there is no evidence to support the use of galactose in children with FSGS, either pre- or post-transplant. Future studies to investigate the role of galactose as preemptive therapy to decrease the risk of post-transplant FSGS recurrence may be useful.     

(iii) Biomechanics of the knee and TKR

The principal aim of a total knee replacement (TKR) is to restore painless movements of the knee joint. Osteoarthritis, along with other pathologies that damage the articular surface of the knee, results in painful limitation of knee movement and alteration of shape and alignment of the joint. Restoration of the functional anatomy of the knee, including alignment, soft tissue balancing and restoration of the joint line, are integral to improving function. Factors that ensure long-term survival of the replaced knee have to be addressed while performing this procedure. Biomechanics of the knee and its restoration are key to improving both function and survival of a total knee replacement. Screw home movement in terminal extension and femoral roll back in flexion are unique to the knee joint. The patella improves extensor function by increasing its lever arm. Implant designs available include femoral components of fixed or multiple radii, high flexion knee replacements, posterior cruciate retaining or substituting designs and fixed or mobile tibial inserts. Computer navigation has been used to achieve accurate bone alignment and soft tissue balancing. Further research on these advances is essential to define their role in improving the results of TKR.     

Assessment of the kinetics of Treponema pallidum dissemination into blood and tissues in experimental syphilis by real-time quantitative PCR

Little is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measure Treponema pallidum DNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components. T. pallidum DNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 x 10(7) to 2 x 10(8) organisms. In five rabbits, T. pallidum DNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits. T. pallidum DNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity of T. pallidum to disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.     

Listeria monocytogenes meningitis: an uncommon opportunistic infection in HIV/AIDS

OBJECTIVE: To report an interesting case of meningitis caused by Listeria monocytogenes meningitis in an HIV seropositive individual. MATERIALS & METHODS: A previously healthy 45 years old HIV seropositive man, presented with atypical clinical features of meningitis. Blood and Cerebrospinal fluid (CSF) were obtained for biochemical and microbiological investigations. RESULTS: CSF analysis showed pleocytosis with lymphocytic predominance. Gram stain of CSF was negative; however culture yielded growth of gram positive bacilli with tumbling motility. Based on relevant biochemical tests the isolate was identified as Listeria monocytogenes. Patient was treated with i.v. ampicillin and recovered completely. CONCLUSION: Listeriosis is relatively rare in HIV/AIDS among the immunodeficient populations. Atypical clinical and laboratory findings make the diagnosis difficult and these infections may go undiagnosed. Since it is easily treated with readily available antibiotics, it is important to diagnose them at the earliest and thereby prevent treatment failure.     

Mapping antigenic diversity and strain specificity of mumps virus: a bioinformatics approach

Mumps is an acute infectious disease caused by mumps virus, a member of the family Paramyxoviridae. With the implementation of vaccination programs, mumps infection is under control. However, due to resurgence of mumps epidemics, there is a renewed interest in understanding the antigenic diversity of mumps virus. Hemagglutinin-neuraminidase (HN) is the major surface antigen and is known to elicit neutralizing antibodies. Mutational analysis of HN of wild-type and vaccine strains revealed that the hypervariable positions are distributed over the entire length with no detectable pattern. In the absence of experimentally derived 3D structure data, the structure of HN protein of mumps virus was predicted using homology modeling. Mutations mapped on the predicted structures were found to cluster on one of the surfaces. A predicted conformational epitope encompasses experimentally characterized epitopes suggesting that it is a major site for neutralization. These analyses provide rationale for strain specificity, antigenic diversity and varying efficacy of mumps vaccines.     

Temporal complexity and heterogeneity of single-neuron activity in premotor and motor cortex

The relationship between neural activity in motor cortex and movement is highly debated. Although many studies have examined the spatial tuning (e.g., for direction) of cortical responses, less attention has been paid to the temporal properties of individual neuron responses. We developed a novel task, employing two instructed speeds, that allows meaningful averaging of neural responses across reaches with nearly identical velocity profiles. Doing so preserves fine temporal structure and reveals considerable complexity and heterogeneity of response patterns in primary motor and premotor cortex. Tuning for direction was prominent, but the preferred direction was frequently inconstant with respect to time, instructed-speed, and/or reach distance. Response patterns were often temporally complex and multiphasic, and varied with direction and instructed speed in idiosyncratic ways. A wide variety of patterns was observed, and it was not uncommon for a neuron to exhibit a pattern shared by no other neuron in our dataset. Response patterns of individual neurons rarely, if ever, matched those of individual muscles. Indeed, the set of recorded responses spanned a much higher dimensional space than would be expected for a model in which neural responses relate to a moderate number of factors-dynamic, kinematic, or otherwise. Complex responses may provide a basis-set representing many parameters. Alternately, it may be necessary to discard the notion that responses exist to "represent" movement parameters. It has been argued that complex and heterogeneous responses are expected of a recurrent network that produces temporally patterned outputs, and the present results would seem to support this view.     

Reference frames for reach planning in macaque dorsal premotor cortex

When a human or animal reaches out to grasp an object, the brain rapidly computes a pattern of muscular contractions that can acquire the target. This computation involves a reference frame transformation because the target's position is initially available only in a visual reference frame, yet the required control signal is a set of commands to the musculature. One of the core brain areas involved in visually guided reaching is the dorsal aspect of the premotor cortex (PMd). Using chronically implanted electrode arrays in two Rhesus monkeys, we studied the contributions of PMd to the reference frame transformation for reaching. PMd neurons are influenced by the locations of reach targets relative to both the arm and the eyes. Some neurons encode reach goals using limb-centered reference frames, whereas others employ eye-centered reference fames. Some cells encode reach goals in a reference frame best described by the combined position of the eyes and hand. In addition to neurons like these where a reference frame could be identified, PMd also contains cells that are influenced by both the eye- and limb-centered locations of reach goals but for which a distinct reference frame could not be determined. We propose two interpretations for these neurons. First, they may encode reach goals using a reference frame we did not investigate, such as intrinsic reference frames. Second, they may not be adequately characterized by any reference frame.