Evidence for two separate vasoconstriction-mediating nucleotide receptors,both distinct from the P2X-receptor,in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides

Summary Uridine 5-triphosphate- (UTP-) and adenosine 5-triphosphate-(ATP) induced vasoconstriction was studied in the rabbit basilar artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure.Serotonin, histamine and noradrenaline caused concentration-dependent vasoconstriction, with potency decreasing in that order. Of the nucleotides tested, UTP, UDP, UMP, CTP, ATP, ADP, adenosine 5-O-(3-thio)triphosphate (ATPS), and ,-imido adenosine 5-triphosphate (AMP-PNP) elicited concentration-dependent vasoconstriction, whereas AMP, 2-methylthio-ATP, , -methylene-ATP and ,-methylene-ATP up to 10^–3 mol/l caused no or only a very small increase in perfusion pressure. The order of potency of the pyrimidine nucleotides was: UTP = UDP UMP = CTP; that of the purine nucleotides was: ATPS > AMP-PNP > ATP > ADP > 2-methylthio-ATP = , -methylene-ATP = ,-methylene-ATP. The vasoconstrictor effects of UTP and ATP were not or only to a minor degree influenced by: phentolamine; a mixture of atropine, diphenhydramine and methysergide; indometacin; nordihydroguaiaretic acid; denervation by 6-hydroxydopamine; or mechanical removal of endothelium. Prolonged exposure to ,-methylene-ATP elicited only a very small vasoconstriction and did not change the constrictor effects of UTP or ATP. Prolonged exposure to ATPS elicited marked vasoconstriction; subsequently, responses to ATP were reduced whereas those to UTP were, if anything, slightly enhanced. Reactive blue 2 reduced neither the UTP- nor the ATP-induced vasoconstriction. ATP 10^–3 mol/l elicited marked additional vasoconstriction after precontraction with UTP 10^–3 mol/l, whereas UTP elicited only a very small additional vasoconstriction when its concentration was doubled from 10^–3 to 2 × 10^–3 mol/l.It is concluded that, in the rabbit basilar artery, the vasoconstrictor response to UTP is mediated by a pyrimidine nucleotide receptor which is distinct from the P₂-purinoceptor, and that the vasoconstrictor response to ATP is mediated by a P₂-receptor which is distinct from the known P₂-subtypes.Send offprint requests to I. v. Kügelgen at the above address     

Cultured chick sympathetic neurons: ATP-induced noradrenaline release and its blockade by nicotinic receptor antagonists

The ATP-induced increase in tritium outflow from cultured chick sympathetic neurons prelabelled with [³H]-noradrenaline was investigated.Seven days-old dissociated cell cultures of embryonic paravertebral ganglia, loaded with [³H]-noradrenaline (0.05 M), were superfused in the presence of (+)-oxaprotiline and exposed to ATP, ATP-analogues, or 1,1-dimethyl-4-piperazinium (DMPP) for 2 min. ATP (3 LM-3 mM), 2-methylthio-ATP (3–100 M), as well as DMPP (10 and 100 M) induced a significant overflow of tritium. The EC₅₀-value of ATP was 20 M. Both the ATP-induced and the DMPP-induced tritium overflow was Ca²⁺-dependent and sensitive to tetrodotoxin (0.3 M) and -conotoxin (0.1 M); in addition, it was inhibited by the ₂-adrenoceptor agonist 5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline (UK-14,304; 1 M). The effects of ATP and DMPP were not additive. The ATP-induced as well as the DMPP-induced overflow of tritium was diminished by the P₂-purinoceptor antagonists suramin (300 M) and reactive blue 2 (3 M); in all 4 cases, the inhibition amouted to approximately 40%. The tritium overflow induced by ATP or DMPP was almost abolished by the nicotinic receptor antagonist mecamylamine (10 M) and markedly inhibited by hexamethonium (100 M). Neither ATP nor electrical stimulation caused an overflow of tritium from cultures loaded with [³H]-choline.The results suggest that ATP at molar concentrations induces noradrenaline release from cultured chick sympathetic neurons via an action on a subclass of the nicotinic cholinoceptor.     

Bone tissue reactions to periodontal dressings.

78 rats weighing 180–200 g were used to assess the bone tissue responses to three periodontal dressings (Coe-pak, Peripac and Ward's Wondrpak). The dressings were implanted subscutaneously on periosteal covered and denuded bone. Sham operated animals served as controls and a comparison btween the responses produced by the three dressngs were made.
In one series the dressings remained in situ for 3, 7, 14, 30 and 90 days. Osteocyte damage of varying extent was recorded for all materials. Remodelling of the bone surface adjacent to the dressing was observed. Bone resorption was never foud in the gournd defect produced to denude the bone tissue, but repair of the defect by bone formation was observed after long observation periods. This repair was retarded in some animals were Ward's Wondrpak had been implanted.
In another seiries Ward's Waondrpak was implanted against bone for three days, then re-operated to remove the dressing and the defect allowed to heal for 30 days. The test group exhibited empty bone lacunae and the repair of the defect was retarded or lacking.     

Societal cost of cancer in Norway –Results of taking a broader cost perspective

BackgroundThe broader cost consequences of diseases may be of interest for a wide range of stakeholders. We aimed to estimate all relevant societal costs of cancer and to provide insight into the relative magnitude of the different cost categories.MethodWe used data from eight different health and work-related registries in Norway. Direct, indirect, and intangible costs (value of lost life years) were estimated over a period of one year with a combination of a top-down and a bottom-up costing approach.ResultsThe indirect costs (EUR 1,997 million per year) are almost as high as direct costs (EUR 2,154 million), and the value of lost life years and quality of life represents the greatest cost related to cancer (EUR 18,200 million). In addition, cancer is associated with other costs which are commonly omitted from cost-of-illness analyses, including informal nursing (EUR 306 million), patient time costs (EUR 85 million), and excess costs of using public funds (EUR 439 million). Breast and cervical cancer had relatively high work absenteeism costs, while pancreatic and lung cancer had relatively high production costs due to premature deaths.DiscussionDirect health care costs represent small proportions of the total societal costs of cancer. Costs commonly omitted in cost-of-illness analyses represent a significant cost and should be measured and valued in these analyses.     

Genetic and epidemiological relationships among Campylobacter isolates from humans

84 Campylobacter jejuni isolates from Swedish patients with domestic infection were characterized with pulsed-field gel electrophoresis (PFGE), and the subtype information considered in relation to epidemiological data. Based on pattern combinations from restriction cleavage with SmaI and SalI, 52 different PFGE types were identified. Types with an average pattern similarity of at least 82% and 63% were assembled in groups and clusters, respectively. The 2 largest clusters included 71% of the isolates. The distribution in time varied between different groups and clusters, where some were isolated sporadically during the whole period and others appeared more concentrated in time. Types in 1 cluster were significantly more often isolated in summer than other types in the study. Isolates from children showed lower pattern similarity to other isolates than isolates from adults. Sets of type and time related cases, possibly representing small outbreaks, were identified when indistinguishable PFGE patterns were found in isolates from temporally related cases. Our results indicate that although a large number of genotypes may be found among C. jejuni strains infecting humans, a large proportion of these may be genetically related, and that different genotypes may appear during different seasons and infect individuals of different ages.     

Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects

OBJECTIVE: Studies to prove a relationship between fatigue and immunological, inflammatory, or other disease characteristics of systemic lupus erythematosus (SLE) have shown no consistent findings. To further elucidate the basis for fatigue in SLE, we examined the affective states, personality traits, and mental health status in an unselected group of patients with SLE. METHODS: Fifty-seven Caucasian patients with SLE were examined. Fatigue was measured by the Fatigue Severity Scale. Personality traits and psychological function were evaluated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the affective states by Beck Depression Inventory, and mental health status by the General Health Questionnaire version 30 (GHQ-30). RESULTS: Fatigue was closely associated with high scores on subscales Depression (D-2) and Hysteria (Hy-3) on MMPI-2 (R2 = 0.31; p = 0.0002), as well as with high scores on BDI (R2 = 0.22; p = 0.0006) and GHQ (R2 = 0.33; p < 0.0001). CONCLUSION: Fatigue does not seem to be caused by any easily recognizable single or multiple factor(s) of an inflammatory or immunological state. Our results point to fatigue being a multifaceted phenomenon where several psychosocial factors are strongly related, and indicate that fatigue is part of a complex response to chronic disease.     

Long-term follow-up in patients treated by stent implantation for post-ablation pulmonary vein stenosis

Purpose

Symptomatic severe pulmonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF) is a rare but well-recognized complication. Treatment options include pulmonary vein angioplasty with or without drug eluting balloons or angioplasty with stent implantation. The treatment of choice is unclear. In our center, pulmonary vein stenting is the treatment of choice for significantly stenotic veins. We present the long-term clinical outcome of 9 patients treated with stent implantation.

Methods

Between 2001 and 2015, 3048 patients with AF were treated with catheter ablation at our institution, of which 9 developed symptomatic PVS. A total of 11 PVS were treated. Pre-procedural imaging (CT, MR, transesophageal echocardiography, angiography) was performed in all patients.

Results

Mean time from ablation to stenting was 18 months. Three patients had recurrent pneumonia and the remaining reduced functional capacity (NYHA 2). All patients were in functional capacity NYHA 1 (p?<?0.05) after a mean follow-up of 64 (18–132) months. Three patients still had paroxysmal AF, of which two have undergone repeated ablation.

Conclusions

Symptomatic PVS after AF ablation can be successfully treated by stent implantation with durable results and good clinical outcome. AF ablation is still a feasible option after stent deployment.

     

The PAS positive material in gastric cancer cells of signet ring type is not mucin

Purpose

The purpose of this study is to assess the exocrine and neuroendocrine properties of tumour cells in diffuse gastric cancer with signet ring cell differentiation.

Material and methods

Mucin mRNA and protein expressions (MUC1, 2, 3, 4, 5AC, 6 and MUC13) were assessed by immunohistochemistry and in situ hybridization. The neuroendocrine properties were evaluated by protein and mRNA expression of the general neuroendocrine markers chromogranin A and synaptophysin.

Results

No MUC expression was observed in signet ring tumour cells including the amorphous substance in any of the nine cases. All cases showed immunoreactivity to synaptophysin, and seven out of nine cases immunoreactivity to chromogranin A in signet ring and non-signet ring tumour cells. Chromogranin A mRNA expression was observed in tumour cells in all samples with retained mRNA.

Conclusions

The lack of MUC protein and mRNA in signet ring tumour cells suggests the amorphous substance is not mucin. The lack of MUC mRNA expression in non-signet ring tumour cells questions exocrine differentiation in this tumour group. The abundant protein expression of the general neuroendocrine markers CgA and synaptophysin, and mRNA expression in tumour cells strengthens the hypothesis that this tumour group may be of neuroendocrine origin.     

Swedish dentists' decisions on preparation techniques and restorative materials

This study aimed at mapping the preparation techniques and restorative materials that Swedish dentists are using for primary approximal and occlusal carious lesions. It involved sending a pre-coded questionnaire to a random sample of 923 dentists, with eight items concerning approximal and occlusal restorative preparation techniques and dental materials. Responses were received from 651 (70.5%) dentists. To restore a primary approximal carious lesion in an adolescent with low caries activity and good oral hygiene, the tunnel preparation was chosen by 48% of the dentists, the saucer-shaped preparation by 32%, and the traditional Class II preparation by 20%. The most common preparation technique for restoring an occlusal carious lesion was removal of the carious part only, which was chosen by 74% of the dentists. For a lower second molar with a minor occlusal caries lesion combined with a suspected dentin lesion as judged radiographically, about half of the dentists chose to restore the carious part only and 27% would seal the rest of the fissure system in addition. For a similar lesion with no obvious radiolucency in the dentin, about 1/3 chose the 'no treatment' alternative, 1/3 fluoride treatment, and the rest fissure sealing or other techniques. Composite was used most often and amalgam least often for both approximal and occlusal carious lesions.     

Long-Term Outcome of Laparoscopic Surgery for Pancreatic Neuroendocrine Tumors

Background

As most pancreatic neuroendocrine tumors (PNET) are relatively small and solitary, they may be considered well suited for removal by a minimally invasive approach. There are few large series that describe laparoscopic surgery for PNET. The primary aim of this study was to describe the feasibility, outcome, and histopathology associated with laparoscopic pancreatic surgery (LS) of PNET in a large series.

Methods

All patients with PNET who underwent LS at a single hospital from March 1997 to April 2011 were included retrospectively in the study.

Results

A total of 72 patients with PNET underwent 75 laparoscopic procedures, out of which 65 were laparoscopic resections or enucleations. The median operative time of all patients who underwent resections or enucleations was 175 (60–520) min, the median blood loss was 300 (5–2,700) ml, and the median length of hospital stay was 7 (2–27) days. The overall morbidity rate was 42 %, with a surgical morbidity rate of 21 % and postoperative pancreatic fistula (POPF) formation in 21 %. Laparoscopic enucleations were associated with a higher rate of POPF than were laparoscopic resections. Five-year disease-specific survival rate was 90 %. The T stage, R stage, and a Ki-67 cutoff value of 5 % significantly predicted 5-year survival.

Conclusion

LS of PNET is feasible with acceptable morbidity and a good overall disease-specific long-term prognosis.