Bifid origin of the left vertebral artery

Two patients demonstrating a bifid origin of the left vertebral artery are described. The embryologic origin of this anomaly is reviewed together with diagnostic and therapeutic implications, emphasizing the importance of knowledge and recognition of the anomaly. It is suggested that this anomaly is not as rare as previously thought.     

The outcome of polymicrobial sepsis is independent of T and B cells

The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. Wild-type mice and Rag-1 mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wild-type and Rag-1 mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in blood urea nitrogen and lactate dehydrogenase levels. Survival curves of wild-type and Rag-1 mice after CLP were superimposable, with 35% survival in the wild-type group and 27% survival in the Rag-1 group, respectively (not significant, P = 0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wild-type and Rag-1 mice 8 h after CLP or sham surgery. Compared with sham surgery mice, the highest mediator levels were observed for granulocyte colony-stimulating factor, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein 1, and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.     

5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats

Background and purpose

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT_1A receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT_1A receptors.

Experimental approach

Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg⁻¹) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT_1A receptor antagonist WAY100635 (0.1 mg kg⁻¹) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety.

Key results

Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD.

Conclusion and implications

The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT_1A receptor-mediated neurotransmission.     

Cloning and pharmacological characterization of the dog P2X7 receptor

Background and purpose:

Human and rodent P2X7 receptors exhibit differences in their sensitivity to antagonists. In this study we have cloned and characterized the dog P2X7 receptor to determine if its antagonist sensitivity more closely resembles the human or rodent orthologues.

Experimental approach:

A cDNA encoding the dog P2X7 receptor was isolated from a dog heart cDNA library, expressed in U-2 OS cells using the BacMam viral expression system and characterized in electrophysiological, ethidium accumulation and radioligand binding studies. Native P2X7 receptors were examined by measuring ATP-stimulated interleukin-1β release in dog and human whole blood.

Key results:

The dog P2X7 receptor was 595 amino acids long and exhibited high homology (>70%) to the human and rodent orthologues although it contained an additional threonine at position 284 and an amino acid deletion at position 538. ATP possessed low millimolar potency at dog P2X7 receptors. 2′-&3′-O-(4benzoylbenzoyl) ATP had slightly higher potency but was a partial agonist. Dog P2X7 receptors possessed relatively high affinity for a number of selective antagonists of the human P2X7 receptor although there were some differences in potency between the species. Compound affinities in human and dog blood exhibited a similar rank order of potency as observed in studies on the recombinant receptor although absolute potency was considerably lower.

Conclusions and implications:

Dog recombinant and native P2X7 receptors display a number of pharmacological similarities to the human P2X7 receptor. Thus, dog may be a suitable species for assessing target-related toxicity of antagonists intended for evaluation in the clinic.     

Nonbronchial systemic collateral arteries: significance in percutaneous embolotherapy for hemoptysis

Twenty patients with massive or recurrent hemoptysis underwent percutaneous transcatheter embolotherapy between 1979 and 1986 for the following diseases: cavitary aspergillosis (n = 4); cystic fibrosis (n = 4); tuberculosis (n = 3); bronchogenic carcinoma (n = 3); bronchiectasis (n = 3); small cell lung carcinoma 6 years after irradiation (n = 1); congenital heart disease, after Glenn and Blalock anastomoses (n = 1); and unknown interstitial disease (n = 1). Bronchial arteries were embolized in all but one patient. In nine patients (45%) nonbronchial systemic collateral arteries contributed significantly to areas of pathologic pulmonary tissue and frequently were the major arterial supply. These nonbronchial systemic collaterals included branches of the subclavian and axillary arteries (n = 7), intercostal arteries (n = 5), and phrenic arteries (n = 3) and accounted for 59.5% of the total number of arteries embolized. Recognition and occlusion of nonbronchial systemic collaterals providing blood to hypervascular pulmonary lesions is essential for successful percutaneous embolotherapy of hemoptysis.     

Effect of cessation of tobacco use on the incidence of oral mucosal lesions in a 10–yr follow-up study of 12 212 users

OBJECTIVE: To study the effect of cessation of tobacco use on the incidence of lichen planus, leukoplakia and other oral mucosal lesions.
DESIGN: A 10–yr cohort study in a rural population of Ernakulam district, Kerala, India.
MATERIAL AND METHODS: Some 12 212 tobacco users were interviewed and examined in a basetine survey and re-examined annually for 10 years. At each examination they were exposed to health educational programs to encourage them to quit their tobacco use. The incidence rates were calculated using person-years method among those who stopped their tobacco use and all others.
RESULTS: A total of 77 681 person-years of observation accrued among men and 32 544 among women. Among men 6.5% of these and among women 14.4% were in the stopped category. The incidence of oral lichen planus did not show any consistent association with cessation of tobacco habits (incidence ratio I.35) but for leukoplakia there was a substantial drop in the incidence after cessation (incidence ratio 0.3I). Several other tobacco-associated oral mucosal lesions such as oral lichen planus-like lesion, smoker's palate, preteukoplakia, central papillary atrophy of the tongue and leukoedema showed either zero, or very small incidence, after cessation. CONCLUSION: The reported association between tobacco use and lichen planus appears to be indirect but for all other lesions it is direct. The cessation of tobacco use led to a substantial fall in the incidence of leukoplakia and other lesions implying a reduced risk for oral cancer after cessation of tobacco use.     

Brachiocephalic artery dilation by percutaneous transluminal angioplasty

Percutaneous transluminal angioplasty (PTA) was used to dilate stenotic lesions in 38 brachiocephalic arteries in 36 patient. Complete evaluation of the central nervous system blood supply is a prerequisite for the brachiocephalic PTA when cerebral symptoms are present. The femoral artery is the best vascular entry site; use of digital subtraction angiography equipment for arterial mapping is helpful. Balloon diameter should be the same as or slightly wider than the diameter of the normal artery adjacent to the stenotic segment. Spasm was successfully treated with intraarterial injection of nitroglycerin. The only drug therapy consistently used with PTA was aspirin. Complete dilation of the stenosis is the best prevention of thrombotic or embolic complications. In properly selected cases, proximal subclavian artery stenoses can be safely dilated, and the balloon can eventually be placed across the origin of the vertebral artery. Because of potential complications associated with brachiocephalic PTA, indications must be well established, and interventions should not be performed on marginal or asymptomatic stenoses.     

Androgen and retinoic acid interaction in LNCaP cells, effects on cell proliferation and expression of retinoic acid receptors and epidermal growth factor receptor

Background

Modulation of the expression of retinoic acid receptors (RAR) α and γ in adult rat prostate by testosterone (T) suggests that RAR signaling events might mediate some of the androgen effects on prostate cells.

Method

In this study, we examined the interactions between T and retinoic acid (RA) in cell growth of human prostate carcinoma cells, LNCaP, and their relationship with the expression of RAR and epidermal growth factor receptor (EGF-R).

Results

Both T and RA, when administered alone, stimulated³H-thymidine incorporation in LNCaP cells in a dose-dependent manner; the effect of each agent was reciprocally attenuated by the other agent. Testosterone treatment of LNCaP cells also resulted in dose dependent, biphasic increases in RAR α and γ mRNAs; increases paralleled that of³H-thymidine incorporation and were attenuated by the presence of 100 nM RA. These results suggest a link between RAR signaling and the effect of T on LNCaP cell growth. Gel electrophoretic mobility shift assays revealed the presence of putative androgen responsive element (ARE) in the promoter region of RAR α gene, suggesting that a direct AR-DNA interaction might mediate the effects of T on RAR α gene. Furthermore, treatment of LNCaP cells with 20 nM T resulted in an increase in EGF-R. In contrast, EGF-R was suppressed by 100 nM RA that also suppressed the effect of T.

Conclusions

Current results demonstrate interactions between T and RA in the expression of RARs and cell growth in LNCaP cells. The presence of putative ARE in the promoter of the RAR α gene suggests that AR-DNA interaction might mediate the effects of T on RAR α gene. The opposite effects of T and RA on the expression of RAR and EGF-R suggest that signal events of these receptors might be involved in the interaction between T and RA in the control of LNCaP cell growth.