Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease

Summary In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.     

Quantitative Assessment of Polyethylene Component Position in a Mobile-Bearing Prosthetic Knee,Using a Single Radiograph

Rationale and Objectives. To reduce tibio-femoral misalignment, the polyethylene bearing-component of a new knee prosthesis was allowed limited motion on the underlying metallic component. The object of the work presented here was to develop a suitable radiographic technique for quantifying the in-vivo position of the bearing. By collecting these data at discrete flexion angles, the functional operation of the prosthesis could be determined

Methods. The known geometries between landmarks on the two components were used to produce algorithms for reconstructing their spatial positions from a single radiograph. A custom-designed computer program utilized these algorithms to determine the relative translation and rotation of the polyethylene component

Results. This technique produced typical errors of 0.54 mm translation and 0.56° rotation between the polyethylene component and the underlying metallic component

Conclusions. A practical method has been developed for assessing mobile-bearing motion, in vivo. This method can be applied to other prosthetic devices, or combinations of components, once the requirement for identifiable landmarks has been addressedClinical Relevance. Skeletal and soft-tissue changes in the pathological knee may produce abnormal rotations and translations in the transverse tibial plane. This technique is intended both to validate the design philosophy of a mobile-bearing prosthesis and to provide additional data on any pathological motions, which will have implications for future prosthetic designs.     

Characteristics of Vaginal Microbiome in Women with Pelvic Inflammatory Disease in Korea

Human vaginal microorganisms play an important role in maintaining good health throughout the human life cycle. An imbalance in the vaginal microbiota is associated with an increased risk of pelvic inflammatory disease (PID). This study aimed to characterize and compare vaginal microbial profiles of premenopausal Korean women with and without PID. 74 Korean premenopausal female vaginal samples were obtained; 33 were from healthy women (a control group) and 41 from PID patients. Vaginal fluid samples were collected from the vaginal wall and posterior cervix and then analyzed by 16S ribosomal ribonucleic acid (rRNA) gene-based amplicon sequencing. Results showed a significant difference between the vaginal microbial communities of the two groups (Jensen-Shannon, p = 0.014; Bray-Curtis, p = 0.009; Generalized UniFrac, p = 0.007; UniFrac, p = 0.008). Lactobacillus accounted for the highest percentage (61.0%) of the control group but was significantly decreased (34.9%) in PID patients; this was the most significant difference among all bacterial communities (p = 0.028, LDA effect size = 5.129). In addition, in the PID patient group, species diversity significantly increased (Simpson, p = 0.07) as the proportion of various pathogens increased evenly, resulting in a polymicrobial infection. Similarly, lactate, which constituted the highest percentage of the organic acids in the control group, was significantly decreased in the PID patient group (p = 0.04). The present study’s findings will help understand PID from the microbiome perspective and are expected to contribute to the development of more efficient PID diagnosis and treatment modalities.     

An experimental model of ascending pyelonephritis due toCandida albicans in rats

We developed a new experimental model of ascendingCandida pyelonephritis in female rats with leukopenia and vesicoureteral reflux. Rats were treated transperitoneally with cyclophosphamide (200 mg/kg) to induce leukopenia 3 days before and transurethrally with diluted acetic acid solution to induce vesicoureteral reflux 1 day before inoculation ofCandida albicans strain, ATCC 10259 (containing 10⁷ cells). Microscopy revealed acute pyelonephritis in whichCandida cells invaded from the fornix and/or papilla into the medulla within 3 days after inoculation. Between 7 and 28 days after inoculation, chronic pyelonephritis reached the cortex. The incidence of pyelonephritis increased gradually and was approximately 80% after 7 days.Candida colony counts of bladder urine specimens obtained by direct puncture were significantly greater in rats with pyelonephritis extending into the parenchyma than in those with pyelonephritis located along the pelvis (p<0.01). These results suggest that this rat model shows the characteristic feature of ascending pyelonephritis due toC. albicans and that the severity ofCandida pyelonephritis can be estimated fromCandida counts of bladder urine.     

HIV 10 years later-where do we stand now?

A wide variety of up-to-date results and knowledge were presented at the 10th International AIDS Meeting, Yokohama. Epidemiologically, most interest was focused on the discovery of a new HIV subtype O, which cannot be reliably detected by currently available ELISA kits. Clinically, it is gradually appreciated that one single most important parameter is the viral load; the extent of viral load can help explain many clinical observations. Another eye-catching finding was the report of a clinical follow-up of a group of long-term nonprogressors. If the underlying operative mechanism can be elucidated, we can learn the necessary elements for halting HIV infection progression. Therapeutically, the trend has shifted to combination therapy, preferentially 3-drug combination of 2 RT inhibitors and 1 protease inhibitor. For the vaccine development, many novel vectors were introduced, but their potentials are unknown at present. The successful application of single-cell in situ PCR has changed our perception of HIV infection. This powerful technique can detect a single viral genome inside cells and revealed that a large proportion of cells already harbor HIV genomes soon after the entry of HIV into the body. A direct viral effect may fully explain subsequent T cell depletion without invoking a lot of indirect mechanisms such as apoptosis.     

A novel hnRNP specifically interacts with HIV-1 RRE RNA

We have identified and obtained the full-length clone of RREBP49, a human nuclear factor which specifically interacts with the Rev-responsive element (RRE) sequence of human immunodeficiency virus type 1. Sequence analysis revealed that RREBP49 is highly homologous to hnRNP F protein and contains three repeated RNA-binding domains. Binding assays demonstrated that Rev and RREBP49 bind to different subregions on the RRE sequence and that binding is mutually nonexclusive. Blocking of endogenous RREBP49 expression by an antisense construct increases Rev activity in CV-1 cells, indicating that RREBP49 and Rev may play antagonistic roles in HIV-1 replication. RREBP49 may function as a splicing factor or a nuclear retention factor for unspliced mRNAs. However, only a slight decrease of Rev activity was observed when exogenous RREBP49 was introduced into CV-1 cells by pSVL-RREBP49 expression vector. This may be explained by a high endogenous level of RREBP49 which is above optimal. Alternatively, additional cellular factors may be required for RREBP49-mediated inhibition of Rev.     

Demonstration by lectin cytochemistry of rod and cone photoreceptors in the lamprey retina

Summary Lectin cytochemical analysis was undertaken to examine the distribution of glycoconjugates associated with the short and long photoreceptor cells in the lamprey retina. Concanavalin A bound preferentially to the outer segment region of the short cells. Wheat germ agglutinin bound weakly to both long and short cells. The outer segment regions of the long cells were stained intensely with peanut agglutinin. Pretreatment with neuraminidase to remove sialic acid resulted in decreased binding of wheat germ agglutinin throughout the retina and increased binding of peanut agglutinin to the outer segment region of the short cells and the region of myoid process of the long cells. These results suggest that there is a difference in the distribution of glycoconjugate residues between the long and short cells. A rod-like character of the short cell and a cone-like character of the long are tentatively discussed. Lectin-binding patterns in other retinal regions is also examined.