Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats

BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.     

Utility of consecutive repeat HIT ELISA testing for heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0-0.132, medium = 0.133-0.267, and high = 0.268-0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT.     

Health literacy in patients referred for transplant: do patients have the capacity to understand?

Adequate levels of health literacy are needed for transplant recipients to be able to understand and comply with medical recommendations. However, little is known about health literacy among transplant candidates. Therefore, the purpose of this study was to examine the levels of health literacy and cognitive functioning among patients being evaluated for various types of transplantation. There were 398 patients who completed a required psychological evaluation prior to being listed for transplant. This included a screen for cognitive impairment and limited reading and math ability. The prevalence of limited reading ability was 27.5%, limited math ability was 42.8%, and 30.7% had probable cognitive impairment. Rates of limited reading and math ability and cognitive impairment varied for each type of end‐stage disease. Limited reading ability was related to poorer cognitive functioning. Those with a higher likelihood of limited reading ability included blacks and males. Those more likely to have cognitive impairment included blacks and patients who are older. Results from this study suggest that patients should be regularly screened for health literacy and cognitive impairment. Once patients with difficulties are identified, recommendations can be provided to these patients at a level that they are able to understand.     

Metabolic Demand of Paralympic Alpine Skiing in Sit-Skiing Athletes

Paralympic Alpine Skiing comprises three main categories, namely Standing, Visually Impaired and Sitting, to one of which athletes get classified depending on their individual impairment of ability. An existing sport profile of alpine skiing for able-bodied athletes facilitates the physical preparation process of Standing and Visually Impaired athletes. However, very little is known about performance determinants as well as content and structure of the physical preparation of athletes with congenital or acquired spinal cord injury competing in the Sitting class. The objective of this study was to describe the metabolic demands of Paralympic Alpine Skiing Sitting class athletes using laboratory and field measurements. The study determined maximal oxygen uptake (VO_2max), maximum heart rate (HR_max) and maximal blood lactate concentration ([La^-]) as well as ventilatory thresholds in laboratory testing (n = 6) as well as on-snow in Slalom (SL) carried out in a ski dome, and Giant-Slalom (GS) on a natural slope. On-snow test variables are expressed normalized to laboratory maximum values (%VO_2max, %HR_max). For SL, values reached ~30% VO_2max and ~60% HR_max whereas GS values were slightly higher reaching ~50% VO_2max and ~75% HR_max. Lactate concentration remained close to baseline values for SL and was slightly higher at ~3 mmol·L^-1 for GS. All athletes remained below their second ventilatory threshold and even skied for a long portion of runtime below their first ventilatory threshold. In general, measured metabolic values were lower than reported for able-bodied alpine skiers. However, despite the small and inhomogeneous sample covering all but one sit-skiing classes, strain of sit-skiing appears to be consistent throughout the five sit-skiing classes. Common measures of aerobic or anaerobic performance variables do not suggest further investigations in the field of metabolism for performance determinants in sit-skiing.

Key points

• Metabolic demand and strain of Paralympic sit-skiing is different to able-bodied skiing.
• Measured parameters of VO2max and [La-] are lower in sit-skiers compared to able-bodies skiers.
• Equipment used for sit-skiing is suggested to absorb external forces to some degree, thereby lowering the strain.
• Implications for training focus (e.g. skiing higher volumes with a focus on technique) and the physical conditioning process (aerobic/ anaerobic capacity are suggested to be no performance determinants) may be derived.

Key words: Paralympic winter sports, paraplegia, wheelchair exercise physiology     

Antibody development to Fusobacterium necrophorum in patients with peritonsillar abscess

A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsillar abscess (PTA) aspirates. Previous studies have suggested a role for Fusobacterium necrophorum (FN) in the development of PTA. The purpose of the current study was to explore whether anti-FN antibodies were produced in patients with PTA. We developed a novel immunofluorescence-based method to measure anti-FN antibody levels in acute and convalescent sera from 15 patients with PTA and 47 patients with chronic tonsillar conditions (controls) undergoing acute or elective tonsillectomy, respectively. Bacterial cultures were performed on tonsillar cores and surfaces, pus aspirates, and blood. An increase in anti-FN antibody levels (of at least doubling of the previous level) was observed in 8 of 11 (73 %) PTA patients with FN-positive pus aspirate cultures (FN-positive patients). In contrast, the four FN-negative PTA patients did not have an increase in anti-FN antibody levels (p?=?0.026). The change in anti-FN antibody levels in FN-positive PTA patients was also significantly greater than that for FN-positive electively tonsillectomized patients (p?=?0.0014) and all electively tonsillectomized patients (p?相似文献   

WhatSAP — 2B4 sends mixed messages in the absence of SAP

2B4 (CD244), a member of the SLAM‐related receptor family, has important immuno‐regulatory functions including coactivating the cytotoxicity and cytokine secretion of NK cells. Immune modulation by 2B4 is dependent on the small intracellular signaling molecule SAP. In patients suffering from X‐linked lymphoproliferative disease (XLP1), SAP is nonfunctional, not only abolishing the activating function of 2B4, but rendering this receptor inhibitory. In this issue of European Journal of Immunology, Meazza et al. [Eur. J. Immunol. 2014. 44: 1526–1534.] demonstrate that 2B4‐mediated inhibition in NK cells from XLP1 patients is selective. While the activation of NK cells via ITAM‐based receptors is blocked by inhibitory 2B4, DNAM‐1, and NKG2D‐dependent NK‐cell activation is not affected by SAP deficiency. These findings provide an important insight into the different defective NK‐cell functions in XLP1 patients and demonstrate the differential integration of redundant receptor signaling pathways in NK cells.