[Analysis of the clinical features and misdiagnosis reasons of 17 patients misdiagnosed with IgG4-related disease].

OBJECTIVE: To summarize the clinical characteristics of patients misdiagnosed with IgG4-related disease, to analyze the reasons of misdiagnosis and to improve the clinical recognition of the disease. METHODS: The general data, clinical manifestations, laboratory examination results and pathological features of 17 patients with IgG4-related diseases misdiagnosed outside the hospital were retrospectively analyzed. RESULTS: Among the 17 patients, there were 9 males and 8 females with a median age of 45 years, and the median time from onset to diagnosis was 12 months. Most patients' initial admission department was not rheumatology or immunology department. Six of the 17 patients were eventually diagnosed with lymphoproliferative disease, 4 with autoimmune disease, and 2 with infectious disease, Rosai Doffman disease, desmofibromatosis, highly differentiated mucoepidermoid carcinoma of the bottom of the mouth, hypereosinophilic syndrome, asthma and allergic rhinitis in 1 case each. The typical sites of IgG4-related disease were involved in 14 patients, including 6 cases of parotid gland, 2 cases of submandibular gland, 3 cases of pancreas and 2 cases of retroperitoneal lesions. Serum IgG4 was elevated in 10 patients, serum IgG4/IgG value was higher than 10% in 7 patients, serum IgE was increased in 7 patients, complement was decreased in 4 patients, and eosinophilic granulocytes were increased in 3 patients. Pathological biopsy was performed in 15 patients, and infiltration of lymphocyte was observed in 10 patients, IgG4+ plasma cells were present in 5 patients, the ratio of IgG4+ plasma cells to IgG+ plasma cells was less than 40% in 4 patients and greater than 40% in 1 patient. However, none of the 15 patients had the storiform pattern of fibrosis and obliterative phlebitis. CONCLUSION: A variety of diseases can perform as IgG4-related disease witih typical sites involved, elevated serum IgG4, even can be characterized by pathological IgG4+ plasma cells infiltration. Physicians should pay attention to the differential diagnosis and comprehensively evaluate the patient's clinical manifestations, and laboratory results. Timely and even repeated pathological biopsy is also needed for definite diagnosis.

[Analysis of 20-year survival rate and prognostic indicators of systemic lupus erythematosus].

Objective: To analyze the 20-year survival rate, causes of death and predictors of systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on 217 newly SLE patients who were diagnosed and treated by Peking University People's Hospital before June 2008. The clinical features and serologic data were studied. Survival rate of SLE patients over time, living conditions, causes of death and prognostic indicators of mortality were studied. Results: The 10-, 15-and 20-year cumulative survival rate was 90.3%,88.1%and 79.6%, respectively. Infection and lupus encephalopathy were the main causes of death. Cox regression analysis revealed that lupus nephritis, neuropsychiatric systemic lupus erythematosus and age at the diagnosis were independent risk determinants for mortality. Conclusion: Prognosis of SLE remains to be improved. Early diagnosis, control of SLE organ damage and infection prevention are critical to improve survival of SLE patients.

[A cross-sectional study of the clinical features and physician visit patterns at onset of immunoglobulin G4 related disease].

OBJECTIVE: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD). METHODS: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work. CONCLUSION: In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.

[Clinical characteristics and associated risk factors of cytomegalovirus infection in patients with underlying systemic Rheumatic diseases].

Objective: To retrospectively investigate the clinical characteristics, risk factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV infection, hospitalized from March 2011 to June 2014 in Peking University People's Hospital, were analyzed.Clinical characteristics were summarized and compared in CMV positive and negative groups, to investigate the risk factors for CMV infection.Statistical analyses were conducted with SPSS 20.0 software. Results: A total of 62 rheumatic patients were found to have CMV infection, with 48 regarded as CMV viremia, 7 diagnosed as CMV pneumonia, while the remaining 7 suffered both CMV viremia and pneumonia.Eleven of 62 patients (17.7%) had a fatal outcome.Systemic lupus erythematosus (SLE) was the most commonly underlying disease (41.9%), followed by Sjögren syndrome (16.1%) and systemic vasculitis (12.9%). Lymphopenia and the reduction of CD4+ T lymphocytes, corticosteroids, cyclophosphamide (CTX) or mycophenolate mofetil (MMF), combined use of more than 2 immunosuppressants and other severe underlying infections as risk factors for CMV infection in rheumatic patients.Meanwhile, the total dose of CTX wasn't different significantly between CMV positive and negative groups.Multivariate analysis revealed that large or pulsed dose of corticosteroids, combined use of immunosuppressants, and severe underlying infections remained independent risk factors for CMV infection. Conclusions: Lymphocytes, particularly the CD4+ T subsets, might play a vital role in the regulation and control of CMV infection.Other underlying infections, undergoing large dose corticosteroids therapy or combined use of immunosuppressants could be the risk factors for CMV infection in rheumatic patients.

Differential diagnosis of IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis.

Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Wharton's duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary.

Prominent sympathetic purinergic vasoconstriction in the rabbit splenic artery: potentiation by 2,2'-pyridylisatogen tosylate.

1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 microM or guanethidine 100 microM. Stimulation at a frequency of more than 32 Hz induced both neurogenic and myogenic responses. 2. Prazosin (1 microM) did not significantly affect vascular contractions to electrical stimulation. Desensitization of P2X-purinoceptors with alpha, beta-methylene ATP (alpha, beta-meATP, 3 microM) abolished the contractions to stimulation at 2-8 Hz and inhibited more than 80% of the vascular response at 16 Hz, but it did not significantly change the responses at 32 Hz. Contractile responses at 32 Hz were inhibited by a combination of prazosin and alpha, beta-meATP. Effects of pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid tetrasodium salt (a selective P2X-purinoceptor antagonist) and suramin (a competitive P2-purinoceptor antagonist) on the neurogenic responses were investigated in this study. 3. 2,2'-Pyridylisatogen tosylate (PIT, 0.3-3 microM) significantly potentiated the vasoconstrictions to electrical stimulation at 2-32 Hz in a concentration-dependent manner. Potentiated responses were restored to the control level 30 min after washing. Concentration-dependent response curves for noradrenaline (NA) or alpha, beta-meATP were not significantly changed by 3 microM PIT, and vasoconstriction by adenosine 5'-triphosphate (ATP, 300 microM) was unaffected by PIT. Coomassie brilliant blue-G (1 microM), which shares the potentiating effect on a recombinant P2Y-purinoceptor with PIT (King et al., 1996), did not inhibit or potentiate the purinergically-mediated component of the response to sympathetic nerve stimulation. The selective alpha 2-adrenoceptor antagonist yohimbine (1 microM) also potentiated the vascular responses to electrical stimulation. 4. The present results indicate that ATP evokes postjunctional contractile responses at low and high frequency electrical stimulation of sympathetic nerves supplying the rabbit splenic artery. PIT potentiates the responses to sympathetic (purinergic) nerve stimulation; this appears to be mainly via prejunctional rather than postjunctional actions.

Differential effects of omega-conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries.

1. The effects of omega-conotoxin GVIA (omega-CgTX) and tetrodotoxin (TTX) on vasoconstrictions induced by acetylcholine (ACh) and nicotine were investigated and compared with those induced by periarterial electrical stimulation in the isolated and perfused canine splenic arteries. 2. ACh and nicotine at doses of 0.01 to 1 mumol constricted the splenic artery, dose-dependently. ACh induced consistent responses, but the vasoconstrictor responses to nicotine became significantly smaller with repeated administration of nicotine. 3. Periarterial electrical stimulation produced a vasoconstriction that was abolished by either TTX (30 nmol) or omega-CgTX (3 nmol), but the vasoconstrictor response to nicotine was not significantly affected by the same doses of TTX and omega-CgTX. Inhibitions by TTX and omega-CgTX of ACh-induced vasoconstrictions were small but statistically significant, showing that the percentage inhibition was less than 15%. TTX and omega-CgTX did not affect the vasoconstrictor responses to exogenous noradrenaline (NA). 4. ACh did not produce any vasoconstriction in the preparations treated either with alpha-adrenoceptor antagonists (10 microM bunazosin and 10 microM midaglizole) or with 30 microM guanethidine. NA-induced responses were abolished by alpha-adrenoceptor antagonists, but not affected by guanethidine treatment. 5. Vascular responses to ACh were completely inhibited by 1 mumol hexamethonium. In the preparations treated with 100 nmol nicotine, ACh did not produce any vasoconstriction. However, the NA-induced vasoconstriction was affected by neither hexamethonium nor nicotine treatment. 6. Atropine (1 microM) significantly inhibited but did not abolish the vasoconstrictor responses to ACh. The vascular responses to nicotine and NA were also significantly inhibited by atropine treatment. 7. These results indicate that (1) ACh constricts the splenic artery through the activation of presynaptic nicotinic receptors present on the sympathetic nerves; (2) differential effects of TTX and omega-CgTX on the vascular responses to ACh and nicotine, and to electrical stimulation suggest that the receptor-operated ion channels are mainly responsible for NA release induced by nicotinic receptor stimulation, but N-type VOCCs are responsible for that by electrical stimulation; (3) atropine may have an inhibitory action on nicotine-related responses, in addition to its inhibitory action on NA.

D-1 dopamine receptors mediate dopamine-induced pancreatic exocrine secretion in anesthetized dogs.

Characterization of dopamine (DA) receptor subtypes was examined on the canine exocrine pancreas using selective DA receptor agonists and antagonists in anesthetized dogs. Each drug was injected i.a. in a single bolus fashion. Graded doses of DA (0.01-3 mumol) produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 1 mumol. SCH23390 (3-30 nmol), a selective D-1 DA receptor antagonist, caused a progressive parallel shift to the right in the dose-response curve for DA-induced pancreatic secretion without changes in the maximal response. However, domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize the DA-induced pancreatic exocrine secretion. A Schild analysis of the data indicates that the inhibitory constant value for SCH23390 to inhibit DA-stimulated secretion was 6.9 nmol. In addition, the stimulatory effects of SKF38393 (0.1-10 mumol) and YM435 (0.3-30 nmol), selective D-1 DA receptor agonists, and LY171555 (1-10 mumol), a selective D-2 DA receptor agonist, on pancreatic secretion were demonstrated. The rank order of agonist potency was YM435 > DA > SKF38393 >> LY171555. These results suggest that DA-induced pancreatic exocrine secretion is mediated by activation of D-1 DA receptors.

Effects of YM435, a novel dopamine D1 receptor agonist, on pancreatic exocrine secretion in anesthetized dogs.

The effects of YM435, a novel dopamine (DA) D1 receptor agonist, on pancreatic exocrine secretion were investigated in anesthetized dogs. Each drug was injected i.a. as a single bolus. Graded doses of YM435 (0.3-30 nmol) produced dose-dependent increases in the rate of secretion of pancreatic juice, with a maximum effect at approximately 10 nmol, and with a high concentration of bicarbonate and low concentration of protein. SCH23390 (3-30 nmol), a selective D1 receptor antagonist, caused a progressive parallel shift to the right of the dose-response curve for YM435-stimulated pancreatic secretion without changing the maximum response. Schild analysis of the data indicated that the inhibitory constant (Ki) value was 2.9 nmol, and that SCH23390 inhibited YM435-stimulated pancreatic secretion in a competitive manner. Both DA (0.01-3 mumol) and SKF38393 (0.3-30 mumol), a selective D1 receptor agonist, also increased the secretory rate and bicarbonate concentration, and decreased the protein concentration to the same extent as YM435. These results suggest that YM435 is a potent stimulant of pancreatic exocrine secretion by acting on DA D1 receptors of the pancreas in dogs.

Developmental changes in sympathetic contraction of the circular muscle layer in the guinea-pig vas deferens.

Contractile responses of the circular muscle of the isolated vas deferens to electrical stimulation (10-80 Hz) and to noradrenaline significantly decreased with increasing age in 3-week-, 10-week- and 18-month-old guinea pigs, observed by the cannula insertion method. There were no significant differences in the contractile responses induced by alpha,beta-methylene ATP or BaCl2 between 3 and 10 weeks old, but the responses to alpha,beta-methylene ATP or BaCl2 decreased in 18-month-old guinea pigs. The contractile response to electrical stimulation was monophasic in 3-week-old guinea pigs, a small portion of which remained after the treatment with prazosin. Desensitisation of P2X-purinoceptors with alpha,beta-methylene ATP significantly inhibited the contractile responses to stimulation with relatively low frequencies, and the combination of both prazosin and alpha,beta-methylene ATP abolished the stimulation-induced contractions. In 10-week- and 18-month-old guinea pigs electrical stimulation evoked a transient contraction followed by a second contraction at the offset of the stimulation (the after-response). The after-responses were blocked by prazosin. These results show that the dominant component of sympathetic cotransmission is noradrenaline; a purinergic component also exists in the sympathetic contraction in the circular muscle of the vas deferens in young guinea pigs, but is virtually absent in the later stages of development. The sympathetic contractions of the circular muscles significantly decrease with increasing age and this appears to be due to changes in postjunctional, rather than prejunctional, mechanisms.

Purinergic and adrenergic transmission and their presynaptic modulation in canine isolated perfused splenic arteries.

Vasoconstrictions induced by periarterial electrical stimulation were analysed pharmacologically in the canine isolated perfused splenic artery. Phentolamine enhanced the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Suramin and P2x purinoceptor desensitization with alpha,beta-methylene ATP abolished the phentolamine-enhanced and -resistant vasoconstrictions. alpha,beta-Methylene ATP inhibited the vasoconstrictions at 1 Hz and by exogenous ATP but did not change those at 10 Hz and by exogenous noradrenaline. Suramin reduced the vasoconstrictions by the electrical stimulations and alpha,beta-methylene ATP but did not affect those by exogenous ATP. Prazosin did not affect the vasoconstrictions at 1 Hz but inhibited those at 10 Hz. Rauwolscine enhanced the prazosin-resistant vasoconstrictions. These results suggest that the electrical stimulation at 1 Hz releases purinergic transmitters (ATP or a closely related compound) as a dominant candidate for the vasoconstrictions, and a co-released noradrenaline may inhibit the release of purinergic transmitters through presynaptic alpha 2-adrenoceptors in the canine splenic artery.

Dual actions of glucagon: direct stimulation and indirect inhibition of dog pancreatic secretion.

The secretory actions of glucagon on the exocrine pancreas were examined using two kinds of canine preparations. In the isolated and blood-perfused dog pancreas with venous drainage, i.a. injection of glucagon did not inhibit secretin/cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion, but instead dose dependently enhanced both basal and stimulated pancreatic secretion. Glucagon-induced increase of pancreatic secretion was potentiated by 3-isobutyl-1-methylxanthine. In contrast, i.v. bolus injection of glucagon (3 and 10 nmol/kg) first augmented transiently then suppressed secretin/CCK-8-stimulated pancreatic secretion while simultaneously increasing circulating plasma somatostatin immunoreactivity from 14.2 to 214 fmol/ml in anesthetized intact dogs. The inhibition of secretin/CCK-8-stimulated pancreatic secretion and elevation of plasma somatostatin immunoreactivity induced by glucagon were comparable with those due to somatostatin-14. Thus, these results indicate that glucagon stimulates pancreatic secretion directly; the inhibitory action of glucagon is indirect and appears to be related to a rise in the circulating level of somatostatin immunoreactivity.

Effects of the cyclic nucleotide phosphodiesterase inhibitors, rolipram, 3-isobutyl-1-methylxanthine, amrinone and zaprinast, on pancreatic exocrine secretion in dogs.

The effects of the cyclic phosphodiesterase (PDE) inhibitors, rolipram, 3-isobutyl-1-methylxanthine (IBMX), amrinone and zaprinast on pancreatic exocrine secretion were investigated in anesthetized dogs. Rolipram (1-30 nmol), IBMX (44-440 nmol) or zaprinast (1-10 mumol) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but amrinone (up to 53 mumol) did not. The bicarbonate concentration in pancreatic juice was increased and the protein concentration was decreased by rolipram and IBMX, but neither was affected by zaprinast. Rolipram elicited more than the respective additive secretory response when added together with secretin, although the stimulatory effects of CCK-8 with rolipram were additive. Rolipram and IBMX, but not zaprinast, increased cyclic AMP concentration but did not affect cyclic GMP concentration. These results suggest that rolipram, IBMX and zaprinast have direct secretory properties on pancreatic exocrine glands of the dog, which may be mediated through the increase of intracellular cyclic AMP concentration, by inhibiting PDE activity. Furthermore, the pancreatic PDE enzyme in the dog pancreas may be mainly a type IV.

Effects of KRN2391, a novel vasodilator, on pancreatic exocrine secretion in anesthetized dogs.

The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003-0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of pancreatic juice, with a high concentration of protein and low concentration of bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and nitroprusside increased the cyclic GMP levels in pancreatic tissue together with the increase in pancreatic secretion. Methylene blue decreased pancreatic secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused vasodilator actions. These results suggest that KRN2391 has direct secretory properties on pancreatic exocrine glands of the dog and its nitro moiety has an important role in the stimulation of pancreatic secretion, but the K+ channel opening action or increasing of blood flow rate does not participate in the secretion.

Cardiac electrical responses to catecholamines are differentially mediated by beta 2-adrenoceptors in anesthetized dogs.

We investigated the beta 2-adrenoceptor-mediated effects of atrial and ventricular effective refractory period (ERP), SA node pacemaker activity, and AV conductivity induced by sympathetic nerve stimulation or epinephrine infusion in anesthetized dogs. A beta 2-adrenoceptor antagonist, ICI 118,551 up to 100 micrograms/kg, i.v., inhibited the positive chronotropic and dromotropic responses to sympathetic stimulation but did not shorten the atrial or ventricular ERP, ICI 118,551 also attenuated the positive chronotropic and dromotropic responses and the shortening of atrial ERP in response to epinephrine but not the shortening of ventricular ERP. A selective beta 1-adrenoceptor antagonist, atenolol, inhibited each electrical cardiac response to sympathetic stimulation and epinephrine infusion in a similar manner. These results suggest that beta 2-adrenoceptor-mediated electrical cardiac responses to endogenous catecholamines also exist in addition to the predominant beta 1-adrenoceptor-mediated responses, and that the order of the proportion of beta 2-adrenoceptor-mediated cardiac effects was SA node pacemaker activity much greater than AV conductivity = atrial ERP much greater than ventricular ERP in the dog heart.

Cardiac responses to VIP and VIP-ergic-cholinergic interaction in isolated dog heart preparations.

Whereas i.v. administration of vasoactive intestinal peptide (VIP) to support dogs increased heart rate and decreased systemic blood pressure, sinus rate and contractile force increased in isolated right atria perfused with blood from the support dogs. VIP injected intraarterially into isolated atria induced dose-dependent positive chronotropic and inotropic effects. Intracardiac parasympathetic nerve stimulation attenuated the positive cardiac responses to VIP, but neither propranolol, imipramine, nor tetrodotoxin influenced the responses to VIP. VIP given to isolated left ventricles also increased the contractile force in a dose-dependent manner. However, VIP induced a greater maximum atrial contractility than ventricular contractility. This may indicate that VIP receptor density in the ventricle was lower than in the atrium, as it has recognized that VIP-ergic nerves innervate the right atrium more densely than the left ventricle. We therefore suggest that the positive cardiac responses to VIP, together with the VIP-ergic innervation in dog hearts and vagal activation, attenuate the VIP-mediated responses at site(s) in the cyclic AMP cascade.

Positive chronotropic and inotropic responses to BRL 37344, a beta 3-adrenoceptor agonist in isolated, blood-perfused dog atria.

We investigated the chronotropic and inotropic responses to BRL 37344 (a beta 3-adrenoceptor agonist) and isoproterenol in isolated, blood-perfused dog atria. BRL 37344 (0.1-30 nmol) or isoproterenol (0.001-0.3 nmol) increased the sinus rate and contractile force dose dependently. BRL 37344 was 290 times less potent than isoproterenol to increase sinus rate and 140 times less potent to increase atrial force. Both propranolol and bisoprolol similarly inhibited the positive chronotropic and inotropic responses to BRL 37344 and isoproterenol dose dependently. ICI 118,551 (0.1 and 1 nmol) did not significantly affect the positive cardiac responses to BRL 37344 or isoproterenol. Neither imipramine nor tetrodotoxin significantly affected the positive cardiac responses to BRL 37344. These results suggest that the positive chronotropic and inotropic responses to BRL 37344 are mediated mainly by beta 1-adrenoceptors in the dog heart. It is unlikely that beta 3-adrenoceptors, as previously reported in adipose tissue or gastrointestinal smooth muscle, mediate chronotropic and inotropic responses in the normal dog heart.

Effects of cementum-dentine junction and cementum on the mechanical response of tooth supporting structure.

OBJECTIVES: The aim of the present work is to investigate the effects of cementum-dentine junction (CDJ) and cementum on the stress distribution in the periodontal ligament (PDL) and alveolar bone. METHODS: Based on the anatomical profiles and the recently reported theories about the tooth attachment mechanism, the finite element (FE) model of a mandibular second premolar along with its detailed supporting structures was developed. The effect of CDJ and cementum was evaluated by comparing the resulting stresses of FE models of the second mandibular premolar with and without CDJ and cementum in tooth supporting structure. RESULTS: The stress levels are higher in the structure without CDJ and cementum than that with CDJ and cementum. The function of CDJ and cementum is as a cushion pad decreasing the stress in the PDL and alveolar bone under loading. CONCLUSIONS: As a major result of this study, it can be concluded that the CDJ and cementum significantly influence the stress distribution within the tooth supporting structure. However, most of the reported FE analysis did not take CDJ and cementum into account, which possibly resulted in overestimated stress values in the PDL and alveolar bone. From a bio-engineering perspective, the results of this study provide guidance for the design of dental implants and the application of orthodontic force system as well.

Surface characteristics and in vitro biocompatibility of titanium anodized in a phosphoric acid solution at different voltages.

The surface of commercially pure titanium was modified by anodization treatment in a phosphoric acid solution at different voltages: 100 V, 200 V and 300 V. The surface characteristics of anodic TiO2 layers and their influence on the cell response were investigated. Micrographs by scanning electron microscopy revealed that the dense and uniform oxide layer obtained at 100 V exhibits a nanostructured surface which is similar to the surface of natural tooth cementum. In contrast, porous oxide layers without nanometer features were produced at higher voltages. Thin film x-ray diffraction analysis confirmed the existence of anatase in the oxide layer obtained at 300 V, but not in oxide layers obtained at 100 V and 200 V. The in vitro biocompatibility study of oxide layers demonstrated greater cell adhesion and proliferation of the oxide layer obtained at 100 V compared to the other two kinds of oxide layers.

Sympathetic cotransmission in rabbit saphenous artery in vitro: effect of electric stimulation and potentiation by alpha,beta-methylene ATP.

AIM: To analyze the cotransmission characteristics of contractile responses to electric field stimulation with submaximal voltage and short train in the rabbit saphenous artery. METHODS: Isometric vasoconstriction of the rabbit saphenous arterial rings was recorded, and the sympathetic nerves of the arterial rings were activated with electric field stimulation. RESULTS: Electric stimulation produced contractile responses in a frequency-dependent manner in the rabbit saphenous artery. Selective alpha1-adrenoceptor antagonist, prazosin (1 micromol/L) did not affect the vasoconstriction induced by electric stimulation at 2 Hz significantly, but inhibited 39.9 % - 53.8 % of the vasoconstriction at 8 - 16 Hz. On the other hand, desensitization of the P2X1 receptor with alpha,beta-methylene ATP (3 micromol/L) abolished all the vascular responses induced by stimulation at 2 Hz, and obviously potentiated those induced by stimulation at 16 Hz, but it did not affect the concentration-dependent response curves for exogenous norepinephrine. The vasoconstriction responses induced by electric stimulation were all abolished by the treatment of a combination of prazosin (1 micromol/L) and alpha,beta-methylene ATP (3 micromol/L). CONCLUSION: The sympathetic and purinergic contractile responses can be induced by 2 Hz stimulation, and ATP is the sole transmitter causing the vasoconstriction in the rabbit saphenous artery. Contractile responses to higher frequencies are related to both norepinephrine and ATP. Desensitization of the P2X1 receptor with alpha,beta-methylene ATP potentiates the vascular responses to electric stimulation via a presynaptic mechanism.