Mechanisms of U46619-induced contraction of rat pulmonary arteries in the presence and absence of the endothelium

Background and purpose:

Thromboxane A₂ and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9α, 11α-methanoepoxy prostaglandin F_2α)-induced contraction was examined in endothelium-intact (E+) and denuded (E−) rat pulmonary artery rings.

Experimental approach:

Artery rings were mounted on a wire myograph under a tension of 7–7.5 mN at 37°C and gassed with 95% O₂/5% CO₂. Isometric recording was made by using Powerlab data collection and Chart 5 software.

Key results:

Both E+ and E− contractile responses were sensitive to Rho-kinase inhibition and the chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid]. The E+ response was sensitive to the store-operated calcium channel blockers SKF-96365 {1-[B-[3-(4-methoxyphenyl)propoxy]-4-methoxy-phenethyl]-1H-imidazole hydrochloride} and 2-APB (2-amino ethoxy diphenylborate) (75–100 µmol·L⁻¹). The E− response was sensitive to 2-APB (10–30 µmol·L⁻¹), a putative IP₃ receptor antagonist, and the calcium and chloride channel blockers nifedipine, DIDS (4,4′-diisothiocyanostilbene-2,2′-disulphonic acid) and niflumic acid but was insensitive to SKF-96365. Inhibiting K_V with 4-AP in E+ rings exposed a contraction sensitive to nifedipine, DIDS and niflumic acid, whereas inhibiting BK_Ca exposed a contraction sensitive to mibefradil, DIDS and niflumic acid. This indicates that removal of the endothelium allows the TP receptor to inhibit K_V, which may involve coupling to phospholipase C, because inhibition of phospholipase C with {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 (1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-y]amino]hexyl]– 1H-pyrrole-2,5-dione) switched the E− pathway to the E+ pathway.

Conclusions and implications:

The results from this study indicate that distinct transduction pathways can be employed by the TP receptor to produce contraction and that the endothelium is able to influence the coupling of the TP receptor.British Journal of Pharmacology (2009) 157, 581–596; doi:10.1111/j.1476-5381.2008.00084.x; published online 22 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Acute calcific tendinitis of the longus colli: an imaging diagnosis

Acute calcific retropharyngeal tendinitis or longus colli tendinitis is an uncommon benign condition presenting as acute neck pain. Clinically, it can be misdiagnosed as retropharyngeal abscess, traumatic injury, or infectious spondylitis. The diagnosis is made radiographically by calcification anterior to C1-C2 and prevertebral soft-tissue swelling. We present two cases of this uncommon condition to illustrate the classic findings on CT and MRI. In addition to the typical calcifications anterior to C1-C2, we detected a retropharyngeal effusion in both patients and effusions involving both lateral atlantoaxial joints in one patient, which to our knowledge has not been published in the literature. In both patients, the correct diagnosis was established by prospective review of the radiographic studies. Recognition of the pathognomonic imaging appearance allows for easy diagnosis preventing unnecessary tests and treatment.     

Effects of tebufenozide on some aspects of lake trout (Salvelinus namaycush) immune response

Tebufenozide is a nonsteroid ecdysone agonist that causes premature and incomplete molting in Lepidoptera and is used on crops and in forest spray programs. Lake trout (Salvelinus namaycush) were exposed to one pulse of 0.25 ppm tebufenozide every 3 days (12 pulses in total). Cell ratios and respiratory burst responses of circulating white blood cells (WBCs) as well as head-kidney (HK) WBCs were investigated by using cell observation, Nitro-Blue Tetrazolium tests, and flow cytometry. Endpoints studied suggest a difference in sensitivity between HK and circulating blood cells to tebufenozide and show a stimulation of fish cell function and changes in percentages of cell types. Responses are not associated with a strong stress response as highlighted by the absence of effect on cortisol and blood protein levels. These results and tebufenozide persistence in water warrant further studies on pesticide impact on fish immunity when used on crops or in forest spray programs near lakes and streams.     

Older Chinese people's views on food: implications for supportive cancer care

Objectives. As people face cancer and the end of life, the social, cultural and therapeutic role of food takes on an increasing significance. As part of a larger study involving older Chinese people resident in the UK, we investigated their beliefs about the influence of food on cancer and its role in supportive cancer care.

Design. A two-phase qualitative research study involved older Chinese people identified via Chinese community groups. In phase one, 46 older Chinese people participated in seven focus group discussions. In phase two, semi-structured interviews were conducted in Cantonese or Mandarin with 46 different older Chinese people to elicit their understandings of the role of food in health and illness generally and specifically for those with cancer.

Results. The analyses revealed four main themes: (1) food as ‘therapeutic’; (2) food as ‘risky’; (3) food as supportive and comforting; and (4) beliefs about the lack of culturally appropriate and acceptable food in hospitals. Expectations about the lack of Chinese food and the poor quality and perceived unsuitability of ‘western’ food were regarded as major concerns in relation to hospital admission.

Discussion. Understanding the perceived cultural and therapeutic significance of food and its functions in social exchange is one important aspect of promoting supportive and end-of-life cancer care for minority communities. These views helped explain the diversity and salience of food use in illness for older Chinese people resident in the UK.     

Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer

Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not specifically categorize adjuvant hormonal therapy as being curative in intent. We propose that adjuvant androgen deprivation therapy should now be classified as a treatment of curative intent in patients with poor-prognosis, non-metastatic prostate cancer. By applying a carefully considered definition of cure (based on long-term (10- to 15-year) disease-free survival curves) to the findings from randomized controlled clinical trials that have studied adjuvant hormonal treatments in non-metastatic prostate cancer, we challenged whether this viewpoint should now be considered redundant. According to our review of relevant studies and our definition of cure, goserelin appears to augment cure in a sizeable proportion of men with poor-prognosis non-metastatic prostate cancer when given adjuvant to radical prostatectomy or radiotherapy. Across several trials, the relevant survival curves for the goserelin-treated population became indefinitely flat after long-term follow-up. This indicates that these patients have a mortality risk comparable to the general population without prostate cancer. On the basis of the evidence presented within this review, we believe that, given it can control disease for a long period of time, adjuvant goserelin should be reclassified as a treatment of curative intent for patients with poor-prognosis non-metastatic prostate cancer.     

Whole liver versus split liver versus living donor in the adult recipient: an analysis of outcomes by graft type

BACKGROUND: We studied patient and graft survival rates in adult liver transplant recipients, analyzing outcomes based on donor source (deceased donor [DD] vs. living donor [LD]) and graft type (whole liver vs. partial liver). METHODS: A retrospective database analysis of all adult liver transpants performed at our center over a 7-year period of time. RESULTS: Between 1999 and 2005, 384 liver transplants were performed in adult recipients, either as a whole liver from a deceased donor (DD-WL, n=284), split liver from a DD (DD-SL, n=31), or a partial transplant from a living donor (LD, n=69). DD-SL transplants were performed with a full right or left lobe graft, while LD transplants used the right lobe. Demographic differences in the three groups were most noticeable for lower model for end-stage liver disease scores in LD recipients (P<0.001) and younger donor age in DD-SL recipients (P<0.001). Superior graft survival results were seen in LD recipients versus either DD-WL recipients or DD-SL recipients (P=0.02 and P=0.05, respectively). Multivariate analysis showed hepatitis C (HR=1.53, P=0.05) and hepatocellular carcinoma (HR=1.74, P=0.03) to be significant risk factors for patient survival. Hepatitis C (HR=1.61, P=0.03) and donor age more than 50 (HR=1.64, P=0.04) were significant risk factors for graft survival. However, neither graft type nor donor source were significant independent risk factors for patient or graft survival. CONCLUSIONS: Our data suggests that the status of the recipient is probably a more important determinant of outcome than graft type or donor source.     

Macular thickness assessment in healthy eyes based on ethnicity using Stratus OCT optical coherence tomography

PURPOSE: To assess the variation in macular thickness measurements in healthy Caucasian and African American men and women through Stratus OCT optical coherence tomography (OCT-3). METHODS: One hundred sixty-six eyes of 83 healthy patients underwent complete ophthalmologic examination in this prospective study. Exclusion criteria included a diagnosis of diabetes mellitus, hypertension, intraocular pressure (IOP) greater than 21 mm Hg, history of eye surgery or trauma, or evidence of eye disease. For analysis purposes, the authors excluded those participants in whom OCT signal strength was <7 in each eye. A fast macular thickness protocol consisting of a 6-mm radial scan centered on the fovea was used for the analysis, and the data were analyzed using the t-test for independence and linear regression. Both eyes of each patient were analyzed using the OCT-3, and analysis showed a statistically significant correlation between right and left eyes. Therefore, only one eye from each patient was randomly selected for final correlation and analysis. RESULTS: Mean foveal thickness (MFT) for Caucasians was 32 microm greater than for African Americans (217 vs. 185 microm, respectively; P < 0.001). The MFT was significantly thicker in males than in females (220 vs. 197 microm, respectively; P < 0.001). CONCLUSIONS: The fovea is significantly less thick in African Americans and females than in Caucasians and males. Racial and sexual differences should be considered when interpreting an OCT scan.