Assessment of renal functional phenotype in mice lacking gp91PHOX subunit of NAD(P)H oxidase

To determine the role of endogenous superoxide (O2-) in the kidney, we assessed renal hemodynamics and excretory function in gp91(PHOX) (a NAD(P)H oxidase subunit) gene knockout (KO) mice and compared these findings with those of wild-type (WT) strain C57BL/6 mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances respectively in anesthetized mice (n=8 in each group). There were higher baseline RBF (4.3+/-0.4 versus 2.5+/-0.2 mL/min per gram; P<0.002) and lower renal vascular resistance (RVR) (16+/-1.4 versus 29+/-2.3 mm Hg/mL/min per gram; P<0.0001) in KO compared with WT without a significant difference in mean arterial pressure (MAP) (67+/-2 versus 71+/-2 mm Hg) and GFR (0.66+/-0.09 versus 0.73+/-0.05 mL/min per gram) between the strains. Intravenous infusion of angiotensin II (Ang II) (2 ng/min per gram of body weight) for 30 minutes caused a lesser degree of decreases in RBF (-8% versus -33%) and of increases in RVR (+73% versus +173%) in KO compared with WT. GFR was increased (43%) in KO but not in WT during Ang II infusion. Urinary excretion of nitrate/nitrite was higher in conscious KO (n=5) than in WT (n=5), indicating an increase in nitric oxide bioavailability that could be the cause of high RBF and low RVR in KO. These data indicate that gp91(PHOX), a subunit of NAD(P)H oxidase, plays a regulatory role in the maintenance of renal vascular tone. These results also suggest that the mechanism of Ang II-mediated renal vascular action involves concomitant generation of O2-.     

Chronic Idiopathic Cough: A Discrete Clinical Entity?

STUDY OBJECTIVES: Despite the success of specialist cough clinics, there is increasing recognition of a subgroup of chronic coughers in whom a diagnosis cannot be made even after thorough, systematic investigation. We call this condition chronic idiopathic cough (CIC). The aim of this study is to compare the clinical characteristics of CIC patients with those of coughers in whom a diagnosis has been established (non-CIC) to see if there is a recognizable clinical pattern that distinguishes CIC from non-CIC. DESIGN: Retrospective analysis of the medical records of chronic cough patients. SETTING: The Royal Brompton Hospital Chronic Cough Clinic, London. PATIENTS: One hundred patients with chronic cough referred to the Royal Brompton Hospital Cough Clinic between October 2000 and February 2004. RESULTS: Seventy-one percent of all patients were female. Median age was 57 years (range, 19 to 81 years), with a median duration of symptoms of 48 months (range, 2 to 384 months). The primary diagnoses were CIC (42%), postnasal drip syndromes (22%), gastroesophageal reflux disease (16%), asthma (7%), and others (13%). In CIC patients, the median age at referral, age at onset of cough, and proportion of females did not differ significantly from non-CIC patients. CIC patients had a longer median duration of cough (72 months vs 24 months, p = 0.002), were more likely to report an upper respiratory tract infection (URTI) as the initial trigger of their cough (48% vs 24%, p = 0.0014), and had a significantly lower cough threshold in response to capsaicin (log concentration of capsaicin required to induce five or more coughs, - 0.009 vs 0.592, p = 0.032) than non-CIC patients. CONCLUSIONS: Patients with CIC commonly describe a URTI that initiates their cough, which then lasts for many years, and they demonstrate an exquisitely sensitive cough reflex. We believe that CIC may be a distinct clinical entity with an as-yet unidentified underlying pathology.     

Cellular and molecular pathophysiology in the progression of Parkinson’s disease

Metabolic Brain Disease - Parkinson’s disease (PD) is a neurodegenerative disorder etiologically linked to the loss of substantia nigra (SN) dopaminergic neurons in the mid-brain. The...     

Amebiasis and mucosal IgA antibody against the Entamoeba histolytica adherence lectin in Bangladeshi children

Amebiasis is the third leading parasitic cause of death worldwide, and it is not known whether immunity is acquired from a previous infection. An investigation was done to determine whether protection from intestinal infection correlated with mucosal or systemic antibody responses to the Entamoeba histolytica GalNAc adherence lectin. E. histolytica colonization was present in 0% (0/64) of children with and 13.4% (33/246) of children without stool IgA anti-GalNAc lectin antibodies (P= .001). Children with stool IgA lectin-specific antibodies at the beginning of the study had 64% fewer new E. histolytica infections by 5 months (3/42 IgA(+) vs. 47/227 IgA(-); P= .03). A stool antilectin IgA response was detected near the time of resolution of infection in 67% (12/18) of closely monitored new infections. It was concluded that a mucosal IgA antilectin antibody response is associated with immune protection against E. histolytica colonization. The demonstration of naturally acquired immunity offers hope for a vaccine to prevent amebiasis.     

Immuno-epidemiology of Ascaris lumbricoides infection in a high transmission community: antibody responses and their impact on current and future infection intensity

The role of the humoral immune system in human infection with Ascaris lumbricoides remains unclear. This study documents an epidemiological investigation in a highly endemic community in Vietnam, whereby serum antibody levels were assessed before treatment and after a 6-month reinfection period. These data were examined by correlation with infection status using an age-structured approach in an attempt to help shed light on the role of the humoral immune response. The first part of this study characterized levels of all serum antibody isotypes from the community in response to antigens of both adult and larval A. lumbricoides. Data were assessed in terms of their relation to host age and infection intensity with the aim to provide a broadly detailed account of immune responses to the parasite. In the second part, antibody responses to both life-stages of A. lumbricoides in serum samples collected before anthelmintic chemotherapy were analysed in relation to intensity of re-infection with the parasite 6 months following treatment. The results suggest that antibody responses may not confer protection from current infection or re-infection with A. lumbricoides and may not serve as reliable indicators of future infection intensity. Our results thereby lend support to the theory that immunity to A. lumbricoides may not be based on the humoral immune system.     

Transgenic expression of survivin compensates for OX40‐deficiency in driving Th2 development and allergic inflammation

Survivin, an inhibitor of apoptosis family molecule, has been proposed as a crucial intermediate in the signaling pathways leading to T‐cell development, proliferation, and expansion. However, the importance of survivin to T‐cell‐driven inflammatory responses has not been demonstrated. Here, we show that survivin transgenic mice exhibit an increased antigen‐driven Th2 lung inflammation and that constitutive expression of survivin reversed the defective lung inflammation even in the absence of OX40 costimulation. We found that OX40‐deficient mice were compromised in generating Th2 cells, airway eosinophilia, and IgE responses. In contrast, OX40‐deficient/survivin transgenic mice generated normal Th2 responses and exhibited strong lung inflammation. These results suggest that OX40 costimulation crucially engages survivin during antigen‐mediated Th2 responses. These findings also promote the notion that OX40 costimulation regulates allergic responses or lung inflammation by targeting survivin thereby enhancing T‐cell proliferation and resulting in more differentiated Th2 cells in the allergic inflammatory response.     

Prophylactic Dose of Neem (Azadirachta indica) Leaf Preparation Restricting Murine Tumor Growth is Nontoxic,Hematostimulatory and Immunostimulatory

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).     

Clinical performance of the H. PYLORI QUIK CHEK™ and H. PYLORI CHEK™ assays,novel stool antigen tests for diagnosis of Helicobacter pylori

European Journal of Clinical Microbiology & Infectious Diseases - Infection with Helicobacter pylori is a global health issue, and rapid and accurate testing is a key to diagnosis. We aimed to...     

Solitary sacral osteochondroma without neurological symptoms: a case report and review of the literature

Purpose

To report a case of solitary sacral osteochondroma without neurological symptoms and describe the en bloc excision of the tumour, as well as review the literature on osteochondroma involving the sacrum.

Methods

Summary of the background data: although osteochondromas are among the most common benign tumours of the bone, they uncommonly involve the spine. Its occurence in the sacrum is rare, accounting for only 0.5 % of the osteochondromas involving spine. All previous cases of sacral osteochondroma have reported neurological symptoms on presentation.

Case report

A 21-year-old male presented with a palpable, painless mass in the left side of the sacral region of 1 year duration, without neurological symptoms. Radiological studies showed a well-circumscribed lesion with bony osteoid within arising from the sacrum at S3–S4 level left to midline, with features suggestive of osteochondroma. The tumour was excised en bloc through posterior approach. A literature review of sacral osteochondroma was conducted using MEDLINE search of English Literature and bibliographies.

Results

Histopathological studies showed the lesion to consist mature bone trabeculae with active enchondral ossification with cap of normal hyaline cartilage. Literature review yielded only 8 cases of sacral osteochondroma reported earlier.

Conclusion

This is the 9th case of solitary osteochondroma of the sacrum to be reported, the first to be reported without any neurological symptoms, and third case reported for which en bloc excision was performed.