Histopathological studies in two strains of semi-immune mice infected with Plasmodium berghei ANKA after chronic exposure

To mimic a human malaria infection in the endemic condition, two strains of mice (Balb/c and CBA) were infected and treated several times to generate so-called semi-immune status. As previously reported, neither mice (Balb/c and CBA) strain showed cerebral malaria, even in the susceptible C57BL/6 (B6). The significant difference between the mice strains in our previous study was the rate of destruction of uninfected red blood cells (uRBCs) at infection. After the established repeated cycles of infection and treatment and the final challenge with 10⁴ Plasmodium berghei ANKA until minimum Hb, Balb/c and CBA mice were sacrificed. The spleen, liver, brain, kidney, lung, heart, and muscle were removed, stained with hematoxylin–eosin and analyzed with light microscopy. Previous observation suggested that Balb/c destroyed uRBC at much higher rate than the other strains although the parasitemia was very low. Pathological investigation carried out in this study revealed that this destruction was mainly contributed by the uRBCs as no parasite sequestration was observed in any of the organs. However, malaria pigment deposition was observed in spleen and liver of all the semi-immune mice strains. This histopathological study in the severe malaria anemia model, which is difficult to conduct in humans, will be helpful in taking into account different responses to malaria infection when designing therapeutic interventions and vaccine studies.     

Heat shock protein 47: a novel biomarker of phenotypically altered collagen-producing cells

Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that helps the molecular maturation of various types of collagens. A close association between increased expression of HSP47 and the excessive accumulation of collagens is found in various human and experimental fibrotic diseases. Increased levels of HSP47 in fibrotic diseases are thought to assist in the increased assembly of procollagen, and thereby contribute to the excessive deposition of collagens in fibrotic areas. Currently, there is not a good universal histological marker to identify collagen-producing cells. Identifying phenotypically altered collagen-producing cells is essential for the development of cell-based therapies to reduce the progression of fibrotic diseases. Since HSP47 has a single substrate, which is collagen, the HSP47 cellular expression provides a novel universal biomarker to identify phenotypically altered collagen-producing cells during wound healing and fibrosis. In this brief article, we explained why HSP47 could be used as a universal marker for identifying phenotypically altered collagen-producing cells.     

Hip dislocation after modular unipolar hemiarthroplasty

An institutional review board-approved retrospective review of hip fractures in elderly patients treated with a modular unipolar implant was carried out to identify factors predisposing to dislocation of a hemiarthroplasty. The main outcome measure evaluated was dislocation vs nondislocation. Two hundred seventeen patients underwent the surgery, and 174 were available for review at 6 weeks and 144 at 1 year. The incidence of dislocation was 6%. The average time of dislocation after surgery was 19.3 days. Clinical factors significant for dislocation were male sex and mental disease. Radiographic factors in dislocated hips included a smaller femoral neck and contralateral femoral neck offset. The center edge angle was also smaller in the dislocated patients. These patients had a higher mortality rate.     

Is efficacy of repeated intradetrusor botulinum toxin type A (Dysport<Superscript>®</Superscript>) injections dose dependent? Clinical and urodynamic results after four injections in patients with drug-resistant neurogenic detrusor overactivity

Objective

To assess the effects of two different doses of botulinum toxin A (Dysport^®: 500 and 1,000 IU) injected repeatedly into the bladder for the treatment of neurogenic detrusor overactivity (NDO) in terms of safety, durability, and improvement of continence status and urodynamic parameters.

Patients and methods

In this study we analyzed the effects of successive doses of 500 or 1,000 IU of Dysport^®, endoscopically injected into the detrusor muscle. Clinical, urodynamic, and satisfaction assessments were performed at baseline and 6 weeks after each injection. The results of injections and corresponding follow-ups were analyzed and compared with baseline.

Results

Twenty-two patients (13 men and 9 women) with repeated four injections were included, of whom 12 (55%) with mean age 35.7 years (range 16–52 years) received 500 IU of BTX-A and 10 (45%) with mean age 33.8 years (range 18–50 years) received 1,000 IU in each treatment. No statistically significant differences were found in efficacy duration with the two Dysport doses (500 IU: 7.7 months, 1,000 IU: 8.5 months; P > 0.05). Maximum cystometric capacity (MCC), reflex volume (RV), and bladder compliance (BC), and patient satisfaction improved significantly after each treatment compared with baseline values and there were no statistically significant differences after each retreatment for the two treatment groups (P > 0.05).

Conclusions

After repeated injections the effect of BTX-A remained constant. The cause of repeat treatment is relapse of overactive bladder symptoms. Results with the 500 and 1,000 IU doses were interesting and approximately equivalent in terms of duration and efficacy, with better but not significant results when 1,000 IU was used. The optimum dose of Dysport for incontinence secondary to NDO is not yet defined; 1,000 IU probably has a nonsignificant longer effect than 500 IU but may expose the patient to major complications. Further studies evaluating the clinical efficacy of 750 IU of Dysport are necessary.

     

SCA‐LSVD: A repeat‐oriented locus‐specific variation database for genotype to phenotype correlations in spinocerebellar ataxias

Repeat expansion has been implicated in 10 out of 17 candidate genes identified for autosomal dominant cerebellar ataxias (ADCAs)—commonly referred as spinocerebellar ataxias (SCAs). Though genetically distinct, the SCAs share a large number of features that confound their clinical classification. In addition, there is a difference in the prevalence and phenotypic expression of ataxias between different ethnic groups. We have created a new SCA‐locus‐specific variation database (LSVD) that aims to catalog and integrate information on SCAs associated with trinucleotide repeat expansion (SCA1, SCA 2, SCA 3, SCA 6, SCA 7, SCA 8, SCA 12, SCA 17, Friedreich's ataxia [FRDA], and dentatorubral‐pallidoluysian atrophy [DRPLA]) from all over the world. The database has been developed using the Leiden Open (source) Variation Database (LOVD) software (Leiden University Medical Center, Leiden, the Netherlands). The database houses detailed information on clinical features, such as age and symptom at onset, mode of inheritance, and genotype information, pertaining to the SCA patients from more than 400 families across India. All the compiled genotype data conforms to the HGVS Nomenclature guidelines. This would be a very useful starting point for understanding the molecular correlates of phenotypes in ataxia—a multilocus disease in which related molecular mechanisms converge to overlapping phenotypes. The database is accessible online at http://miracle.igib.res.in/ataxia . Hum Mutat 30:1–6, 2009. © 2009 Wiley‐Liss, Inc.