Angiotensin-converting Enzyme Concentration Research Articles

Clinical features of central airway involvement in autoimmune pancreatitis

To the Editors: Autoimmune pancreatitis (AIP) is characterised by a high serum immunoglobulin (Ig)G4 concentration and various extrapancreatic complications, including those of the lung [1]. Therefore, AIP is currently not viewed as a separate disease entity, but as the pancreatic involvement of a systemic IgG4-related disease [2]. We previously reported a patient with AIP showing central airway stenosis and bilateral hilar lymphadenopathy (BHL) similar to sarcoidosis [3]. Following this case, we prospectively identified an additional five patients with AIP who revealed similar airway findings (and BHL) in our department from September 2007 to January 2009. The six patients (including the first patient) met the diagnostic criteria of AIP proposed by Japanese Pancreatic Society in 2006 [1]. In order to update the available clinical and therapeutic information on central airway involvement in AIP, we performed airway biopsies and other examinations in these six patients. All six patients gave their written informed consent for the performance of bronchoscopy and blood sampling. The angiotensin-converting enzyme (ACE) and IgG4 concentrations were measured at Special Reference Laboratories Inc. (Tokyo, Japan), and interleukin (IL)-6 was measured at Mitsubishi Kagaku Bio-Clinical Laboratories Inc. (Tokyo, Japan). Chest computed tomography (CT) was performed with a multidetector row helical CT scanner (LightSpeed VCT; GE Medical Systems, Milwaukee, WI, USA) with both inspiratory and expiratory views [4]. All CT images were reviewed by two radiologists (S. Kawakami and Y. Fujinaga, Shinshu University School of Medicine, Matsumoto, Japan) [4]. Fibreoptic bronchoscopy (BF 1T-240 or 1T-260; Olympus corporation, Tokyo, Japan) was performed, and bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBLB) and bronchial biopsy were achieved according to our routine protocol [5]. The TBLB was carried out in the right upper lobe (S2 and S3) and the bronchial biopsy …

A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and steroid-sensitive nephrotic syndrome in children

Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism correlates with circulating and cellular ACE concentration. Association between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) risk in children is still controversial. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and SSNS susceptibility in children. The relevant investigations were screened from the search engines of PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2011, and eligible studies were synthesized using meta-analysis methods. Ten studies were identified for the analysis of association between ACE I/D gene polymorphism and SSNS risk in children, including seven in Asians, one for Caucasians and two in Africans. There was no markedly positive association between D allele or DD genotype and SSNS susceptibility in Asians, Caucasians and Africans (D: Asians OR = 1.24, p = 0.28; Caucasians OR = 1.61, p = 0.15; Africans OR = 1.61, p = 0.53; DD: Asians OR = 1.72, p = 0.15; Caucasians OR = 1.39, p = 0.48; Africans OR = 1.80, p = 0.56). Furthermore, II homozygous seemed not to play a protective role against SSNS onset for Asians, Caucasians and Africans (Asians OR = 0.95, p = 0.85; Caucasians OR = 0.30, p = 0.11; Africans OR = 0.60, p = 0.65). There was no association between ACE I/D gene polymorphism and SSNS susceptibility in Asians, Caucasians and Africans. However, the conclusions for Caucasians and Africans were less powerful.

Levodopa-induced breathing, cognitive and behavioral changes in Parkinson’s disease

A 78-year-old male, already affected by Parkinson’s disease (PD) for the last 9 years, is the focus of this report. At diagnosis, after a good response to acute dopaminergic challenge, he was started on therapy with levodopa/Carbidopa 100 mg three times/day. At the age of 77, the patient developed daily recurrent respiratory disturbances and confused state, lasting from 2 to 4 h, which required assistance. In one of these episodes, the most severe, he was admitted to our clinic. On admission, he was confused and irritable with visual hallucinations, and dysphonic with irregular breathing as well as signs due to parkinsonism. Four hours later, the patient returned to a normal state: well-oriented, quiet and cooperative, without abnormal movements and with regular breathing. Laboratory tests, performed to exclude systemic causes, showed only a mild kidney insufficiency. Blood tests, including complete blood count, serum electrolytes, glucose, vitamin B12, vitamin E, antinuclear antibodies, lactate dehydrogenase, serum immunofixation, extractable nuclear antibody, paraneoplastic panel and angiotensinconverting enzyme concentrations, were negative or within normal limits. Thyroid, coagulation, and D-dimer and ECG were normal. Chest X-rays and CT were unremarkable. An MRI exam showed a diffused leukoencephalopathy and mild atrophy. At this point, a polygraphic exam during a levodopa challenge test was performed. Fifty minutes after the administration of 300 mg levodopa/Carbidopa, the patient presented irregular breathing and confusion. Ten minutes thereafter, the patient became agitated and uncooperative (see video). This condition lasted 4 h, and then progressively agitation and confusion decreased and breathing became regular. The polygraphy recording did not show EEG, O2-saturation and heart rate modifications, but an irregular respiratory rhythm (Fig. 1). Levodopa therapy was reduced and the episodes disappeared, although increases in bradykinesia and rigidity were observed. In PD, an underlying pulmonary dysfunction of both restrictive, partially responsive to levodopa, and obstructive type, in which levodopa induces significant variations in peak expiratory flow and upper-airway obstruction ratios, has been reported [1]. On the other hand, an acute onset of breath disorders has been described in PD in both onand off-condition [2]. To our knowledge, in on-condition, five cases of levodopa-induced respiratory disorders have been reported [3–6] (Table 1). In all patients, the decrease of dopaminergic therapy resulted in a reduction of the episodes, except for the one in which the treatment with tiapride was effective. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6119-5) contains supplementary material, which is available to authorized users.

The relationship between local renin-angiotensin system and intimal proliferation in an organ culture of human saphenous veins

Local renin-angiotensin system (RAS) is implicated in development of intimal hyperplasia after vein bypass grafting, but little is known about the local angiotensin-converting enzyme (ACE) activity and the local responses of angiotensin II (AngII) in vein graft physiology. An organ culture of human saphenous vein was used as a model of vein graft intimal hyperplasia, and the role of local RAS in the development of neointimal proliferation was studied. Segments of saphenous veins were cultured for 14 days. One group was set as control, another two were cultured in medium with captopril, an ACE inhibitor and losartan, an Ang II receptor antagonist, respectively. All specimens were frozen in liquid nitrogen for ACE activity, histology, and immunohistochemistry studies. The concentration of ACE increased 37% in cultured veins to preculture veins. Immunohistochemical localization identified ACE in the endothelial layer of preculture veins and cultured veins, but at a greater density in the intimal hyperplasia of cultured veins. Captopril and losartan significantly reduced neointimal thickness by 49% and 34%, respectively. These data demonstrate that a positive relationship exist between local RAS and intimal proliferation. The use of ACE inhibitors and Ang II receptor antagonists have clinical significance in the prevention and treatment of vein graft disease.

The Effect of Captopril on the Membrane Properties of Central Neurons In-vitro

Captopril, a potent antihypertensive that acts via inhibition of angiotensin converting enzyme also has apparent central actions. Its effects on membrane properties on particular central neurons in-vitro has therefore been investigated. In the substantia nigra, where there is a high concentration of angiotensin converting enzyme, captopril caused a dose-dependent depolarization without any apparent change in conductance, but possibly requiring the integrity of the dendritic arbour. A similar effect occurred when captopril was applied to neurons in either the thalamus or hippocampus, where levels of angiotensin converting enzyme are relatively low. Further studies with homologues of captopril revealed that the -SH group on the molecule was a prerequisite of the effect observed. It is concluded that the -SH group on the captopril molecule has an electrogenic effect on diverse central neurons, independent of inhibition of angiotensin converting enzyme, but preferentially manifest at the level of the dendrite.

Effect of Corticosteroid Therapy on Ventricular Arrhythmias in Patients with Cardiac Sarcoidosis

Ventricular arrhythmias are one of the main causes of sudden death in cardiac sarcoidosis (CS). Little is known about the efficacy of corticosteroid therapy for ventricular arrhythmias in CS. Thirty-one CS patients presenting premature ventricular contractions (PVCs, ≥300/day) were investigated. Fourteen patients had nonsustained ventricular tachycardia (NSVT). All of patients were treated with corticosteroid, and the initial dosage is 30 mg/day of prednisone, which was tapered over a period of 6 months to a maintenance dosage of 10 mg/day. Twenty-four hour Holter monitoring, signal averaged electrocardiography (SAECG), echocardiography, gallium-67 scintigraphy, serum angiotensin converting enzyme (ACE) and plasma B-type natriuretic peptide (BNP) concentrations were assessed before and after corticosteroid therapy. As a whole, there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. However, the less advanced LV dysfunction patients (EF ≥ 35%, n = 17) showed significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425, P = 0.048) and in the prevalence of NSVT (from 41 to 6%, p = 0.039). Late potentials on SAECG were abolished in 3 patients. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium-67 uptake compared with the advanced LV dysfunction group (EF < 35 %, n = 14). In the advanced LV dysfunction patients, there were no significant differences in these parameters. Corticosteroid therapy may be effective for ventricular arrhythmias in the early stage, but less effective in the late stage.

Modeling the Consistency of Hypoglycemic Symptoms: High Variability in Diabetes

The aim of the present study was to examine symptoms of hypoglycemia, to develop a method to quantify individual differences in the consistency of symptom reporting, and to investigate which factors affect these differences. Participants recorded their symptoms with every episode of hypoglycemia over a 9-12-month period. A novel logistic-type latent variable model was developed to quantify the consistency of each individual's symptom complex and was used to analyze data from 59 subjects (median age, 57.5 years [range, 22-74 years], 65% male, 77% type 1 diabetes) who had experienced 19 or more hypoglycemic episodes. The association between the calculated consistency parameter and age, sex, type and duration of diabetes, and C-peptide and serum angiotensin converting enzyme concentration was examined using a generalized linear model. Analyses were performed under a Bayesian framework, using Markov chain Monte-Carlo methodology. Individuals exhibited substantial differences in between-episode consistency of their symptom reports, with only a small number of individuals exhibiting high levels of consistency. Men were more consistent than women. No other factors affected consistency in patients with normal hypoglycemia awareness. By using a novel stochastic model as a quantitative tool to compare the consistency of hypoglycemic symptom reporting, much greater intra-individual variability in symptom reporting was identified than has been recognized previously. This is relevant when instructing patients on identification of hypoglycemic symptoms and in interpreting symptomatic responses during experimentally induced hypoglycemia.

Scar sarcoidosis： first case report in China

A 54-year-old woman presented with a five-year history of malaise with weight loss and arthralgia of both knee joints. Six months prior to the presentation, an indurated nodule developed at the site of an old scar on the temporal side of left eyebrow. Subsequently, erythema and nodules spread over the trunk and extremities, especially at the sites of old scars on the hands. Physical examination showed bilateral axillary lymphadenectasis, a plaque at the site of an old scar on the temporal side of left eyebrow, a subcutaneous mass at the extensor aspect of the right upper arm, multiple dark-erythematous nodules at the site of scars on the left hand and both soles, few small erythematous papules scattered on the left forearm and trunk. The serum angiotensin converting enzyme concentration was high （82 kU/L）. Computer tomography of thorax showed multiple obscure tubercles in both lungs and swollen lymph nodes in mediastina and axillary fossa, but no hilum pulmonis lymphadenectasis was observed. Histopathology revealed non-caseating granulomas with multinucleated giant cells. Neither acid-fast bacilli nor PAS staining was positive. A diagnosis of scar sarcoidosis was established. The lesions obviously improved after one-month treatment with oral methylprednisolone. This case represents a rare subtype of sarcoidosis that arose in old sears and clinically manifests as scar, nodules,plaques, subcutaneous masses and papules. The reactivation of old scars, which manifests as erythematous swelling and nodules, may highly suggest the diagnosis of sarcoidosis. Key words: Sarcoidosis; Cicatrix; Case reports

Effects of Bosentan Treatment on Angiotensin Converting Enzyme in Monocrotaline Induced Pulmonary Hypertension Rats

❙ABSTRACT❙ Background: Pulmonary artery hypertension is characterized by persistent increase of vascular resistance, and is associated with right ventricle failure. We investigated changes of plasma renin, serum aldosterone, angiotensin converting enzyme (ACE) concentrations, ACE gene expressions and protein contents after bosentan treatment. Methods: Six-week-old male Sprague-Dawley rats were divided into three groups: control (C) group, monocrotaline (M) group, and bosentan (B) group. Groups M and B were subcutaneously administered with 60 mg/kg of monocrotaline. In group B, 20 mg/kg/day of bosentan was administered by gavage twice a day. The rats were sacrificed after 1, 5, 7, 14, and 28 days. Changes of ACE gene expressions were analyzed by reverse transcription-polymerase chain reaction. Also, plasma renin, serum aldosterone, and ACE levels were measured. Results: Serum aldosterone levels were significantly increased in group M compared with group C and significantly decreased after bosentan treatment on day 28. Serum ACE concentrations were significantly decreased compared with group M after bosentan treatment on day 28. Gene expressions of ACE were significantly increased in group M compared with group C on day 5 and significantly decreased after bosentan treatment on day 7 and 14. ACE protein contents significantly increased in group M compared with group C in week 2 and 4. It significantly decreased after bosentan treatment in week 2. Conclusions: The renin-angiotensin system is associated with pulmonary artery hypertension. To investigate the effects of bosentan on the renin-angiotensin system in pulmonary artery hypertension, further studies on the effects of bosentan according to different doses are required in the future. (J Korean Soc Hypertens 2011;17(1):28-36)

Intrarenal Renin Angiotensin System Revisited: ROLE OF MEGALIN-DEPENDENT ENDOCYTOSIS ALONG THE PROXIMAL NEPHRON

The existence of a local renin angiotensin system (RAS) of the kidney has been established. Angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), angiotensin receptors, and high concentrations of luminal angiotensin II have been found in the proximal tubule. Although functional data have documented the relevance of a local RAS, the dualism between biosynthesis and endocytotic uptake of its components and their cellular processing has been incompletely understood. To resolve this, we have selectively analyzed their distribution, endocytosis, transcytosis, and biosynthesis in the proximal tubule. The presence of immunoreactive AGT, restricted to the early proximal tubule, was due to its retrieval from the ultrafiltrate and storage in endosomal and lysosomal compartments. Cellular uptake was demonstrated by autoradiography of radiolabeled AGT and depended on intact endocytosis. AGT was identified as a ligand of the multiple ligand-binding repeats of megalin. AGT biosynthesis was restricted to the proximal straight tubule, revealing substantial AGT mRNA expression. Transgenic AGT overexpression under the control of an endogenous promoter was also restricted to the late proximal tubule. Proximal handling of renin largely followed the patterns of AGT, whereas its local biosynthesis was not significant. Transcytotic transport of AGT in a proximal cell line revealed a 5% recovery rate after 1 h. ACE was expressed along late proximal brush-border membrane, whereas ACE2 was present along the entire segment. Surface expression of ACE and ACE2 differed as a function of endocytosis. Our data on the localization and cellular processing of RAS components provide new aspects of the functional concept of a "self-contained" renal RAS.

Investigation of Association Between Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism Frequency in Turkish Patients with Schizophrenia

the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is of increasing interest in etiology and treatment of various neuropsychiatric disorders. The present study aimed at detecting the incidence of ACE gene I/D polymorphism in patients with schizophrenia living in the Eskisehir region (Turkey) and also at determining whether this illness could be associated to ACE gene I/D polymorphism and serum ACE concentrations. in our study, genomic DNA was studied in a total of 237 individuals, 132 of them having been diagnosed as patients with schizophrenia and 105 of them being used as control subjects. In addition, sera from 31 patients with schizophrenia and 26 healthy subjects were used to compare serum ACE concentrations. By using polymerase chain reaction, we determined the frequency of ACE gene I/D polymorphism and measured the serum ACE concentrations by ELISA. distribution of ACE gene I/D polymorphism and allele frequencies between the control group genotype proportions (II 19%, ID 44%, DD 37%) and the patient group (II 19%, ID 45%, DD 36%) were not significantly different. Serum ACE concentrations were 293.15 ± 23.29 ng/mL in the control group and 362.61 ± 19.96 ng/mL in the patients. It was observed that serum ACE concentrations significantly increased in patients with schizophrenia compared with those of the control group (p < 0.05). However, no significant difference could be observed according to genotypes in serum ACE concentration.

ACE I/D polymorphism affects cognitive function and gray-matter volume in amnestic mild cognitive impairment

To characterize the correlates of cognitive function, serum concentrations of angiotensin converting enzyme (ACE) and brain structure with the ACE insertion or deletion (I/D) polymorphism were analyzed in subjects with amnestic-mild cognitive impairment (aMCI). A group of 48 subjects meeting criteria for aMCI and 36 age-matched control subjects were assessed using a comprehensive battery of standardized neuropsychological tests and magnetic resonance imaging (MRI). The ACE gene's I/D polymorphism was analyzed by means of PCR, and serum ACE concentrations were measured using ultraviolet spectrophotometry. Genotype effects on neuropsychological domains and MRI gray matter volume (GMV) measurements (optimized voxel-based morphometry) were examined using general linear models. The D carriers among the aMCI subjects performed significantly worse on AVLT-delayed recall compared to the I homozygous group. The D carriers had higher serum ACE concentrations than did the I homozygous carriers, though this difference only reached statistical significance in the aMCI group. Compared with the I homozygous carriers, in the aMCI group, D carriers showed smaller GMV of the bilateral middle frontal gyrus, right cuneus, right precentral gyrus, right medial frontal gyrus, right superior frontal gyrus, and left postcentral gyrus. However, there was no significant difference in GMV between I homozygous and D carriers in the normal control group. The study suggests that ACE genotype has considerable effect on the cognitive performance of aMCI subjects, particularly episodic memory, serum activity of ACE, and the structure of specified brain regions. The ACE D allele may be a genetic risk factor for greater atrophy of gray matter in aMCI.

Pilot study to examine the association between angiotensin-converting enzyme genotype and fluid retention in humans

Following ingestion of a variety of drinks, subsequent urine excretion in humans shows large variability.1 The reasons for this are currently unknown. Aldosterone, the end product of the renin angiotensin aldosterone system (RAAS), increases sodium and water re-absorption in the kidney. Circulating concentrations of angiotensin-converting enzyme (ACE), a key component of the RAAS, are affected by a polymorphism in the ACE gene involving the deletion (D) or insertion (I) of a 287 base pair sequence, with DD genotypes resulting in higher circulating concentrations of ACE.2 Following ethical approval, 29 healthy Caucasian males participated in this investigation. Participants arrived at the laboratory hydrated after an overnight fast. Following arrival, participants' height and body mass were measured before a 15-min supine rest period. Total body water was measured before a fingerprick blood sample was obtained in order to determine ACE genotype. Participants then provided a urine sample before ingesting 600 ml of a commercially available sports drink over a period of 5 min. A further urine sample was obtained 60 min later. Urine samples were analysed for osmolality and sodium concentration. The I allele (corresponding to either ID or II genotypes) was found in 12 participants and 17 participants were found not to have the I allele (corresponding to a DD genotype). Baseline characteristics of the two groups were the same (p&gt;0.05) with the exception of height. Pre-ingestion urine volume and osmolality were the same for both groups (p&gt;0.05). Following ingestion of the drink, urine volume amounted to 420±258 ml for those with the I allele and 337±160 ml for those without the I allele (p=0.293). This pilot study found that, although not statistically significant, participants with the I allele had a lower urine volume than those without the I allele, amounting to a reduction of approximately 80 ml (19%). Further investigations are now warranted in a larger participant cohort to determine whether the ACE genotype is statistically associated with fluid retention after ingestion.

Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin–angiotensin system

We examined the impact of acute myocardial ischemia followed by reperfusion (AMI-R) on local and circulating renin-angiotensin system (RAS) in a swine model. The mid left anterior descending artery (n = 6) was occluded for 1 h, followed by reperfusion for 2 h. Monastryl blue/triphenyl tetrazolium chloride staining identified the area-at-risk (AAR) and infarction. A second group of control animals underwent sham operations (C: n = 4). Myocardial expression of angiotensinogen (AGT), renin, chymase, angiotensin converting enzyme (ACE), angiotensin II (Ang II), Ang II type1 receptor (AT1R) and Ang II type 2 receptor (AT2R) in the AAR and the non-ischemic left ventricle (NLV) was assessed. Serum level of these proteins at baseline and at the end of reperfusion was also examined. Chymase (P < 0.05), ACE (P < 0.05), Ang II (P < 0.05), AT1R (P < 0.05) and AT2R (P < 0.05) expressions were found to be significantly higher in the AAR compared to the NLV and C whereas no significant differences were found for AGT (P = 0.58) and renin (P = 0.38). Serum concentration of ACE was significantly higher at the end of reperfusion than at baseline (P < 0.01), whereas no significant difference was found for chymase (P = 0.71), AGT (P = 0.57) and Ang II (P = 0.19). Immunohistochemistry of myocardial sections demonstrated significantly higher expression of ACE (P = 0.02), AT1R (P = 0.01), AT2R (P = 0.02) and Ang II (P < 0.01) in the AAR as compared to the NLV, whereas no significant difference was found for renin (P = 0.39). In conclusion, AMI-R resulted in significantly higher expression of specific cardiac RAS components in AAR compared to the NLV in the acute period.

NEUROSARCOIDOSIS WITH DIENCEPHALITIS AND ANTI-Ma2 ANTIBODIES

Anti-Ma2 antibodies (Ma2-Ab) were originally described in men with testicular cancer and paraneoplastic damage to the limbic system and the diencephalon.1 Fewer than 20 women with Ma2-Ab have been identified, and those had lung or breast cancer.1–3 We report a case of a woman with the typical clinical and immunologic presentation of diencephalitis associated with Ma2-Ab. Unexpectedly, neuropathologic findings were characteristic of neurosarcoidosis. ### Case report. A 52-year-old woman had an unexplained weight gain of 30 kg between December 2005 and June 2006. Endocrinal evaluation had identified panhypopituitarism. Excessive daytime sleepiness associated with atonic episodes appeared in mid 2008. The CSF level of hypocretin was normal, and a polysomnogram showed excess slow waves but normal sleep architecture. Brain MRI showed T2 hypersignal and gadolinium enhancement in the diencephalon (figure, A and B). The CSF was mildly lymphocytic (20/mm3) with elevated protein concentration (1.56 g/L). Bacterial cultures and viral serologies were negative. Antibodies against nuclear antigens, DNA, neutrophil cytoplasm, thyroid, mitochondria, actin, transglutaminase, endomysium, glutamate decarboxylase, and gliadin were all negative. Angiotensin converting enzyme concentration was normal in serum. CSF onconeuronal antibody detection by the dot blot assay (Ravo Diagnostika GmbH, Freiburg, Germany) revealed a strong reaction against the Ma2 antigen. The presence of Ma2-Ab in both CSF and (weakly) in serum …

Sarcoidosis Following Cushing's Syndrome: A Report of Two Cases and Review of the Literature

Cushing's syndrome is characterized by excessive elevation of glucocorticoid concentrations. In rare cases, the treatment of Cushing's syndrome may result in unmasking or aggravation of diseases responsive to glucocorticoid medication. We report two cases of sarcoidosis following Cushing's syndrome. A 43 year-old male developed cutaneous sarcoidosis and mediastinal lymphadenopathy after resection of an ACTH-secreting pituitary microadenoma. A 32 year-old female showed cutaneous sarcoidosis, arthralgia, mediastinal lymphadenopathy and elevation of angiotensin-converting enzyme and interleukin 2-receptor concentrations after traumatic adrenal bleeding, which ceased formerly undiagnosed hypercortisolism caused by an adrenal adenoma. Sarcoidosis seems to be a rare sequel following the treatment of hypercortisolism. Skin affections were present and suggestive for the diagnosis in all reported cases. As some cases are probably missed when skin affections are lacking, a more frequent evaluation of patients after Cushing's syndrome for the possible diagnosis of sarcoidosis might be necessary.

Alterations in biomarkers of endothelial function following on‐pump coronary artery revascularization

Cardiopulmonary bypass (CPB) has been associated with activation and injury of endothelial cells, probably responsible for the systemic inflammatory response syndrome (SIRS) taking place in these patients. We measured plasma concentrations of soluble P-selectin (sP-s), E-selectin (sE-s), tetranectin (TN), vonWillebrand factor (vWF) levels, and angiotensin-converting enzyme (ACE) activity in 31 adult patients undergoing elective coronary artery bypass grafting, just before and up to three days after surgery, and in 25 healthy volunteers. Patients showed higher plasma sP-s and sE-s and ACE concentrations, just before surgery, but significantly lower TN levels, compared with controls. During the first three postoperative days (PD), the concentration of each of the molecules followed a different and independent pattern, although in the third PD, the levels of sP-s, sE-s and ACE were higher and those of vWF and TN lower, compared with the preoperative ones. However, patients had higher sP-s (P=0.06), sE-s (P=0.07), and vWF (P=0.005), but lower TN concentrations (P=0.02) on the third PD compared with controls. CPB is characterised by pronounced changes in plasma sP-s, sE-s, TN, vWF levels, and ACE activity, which are associated with significant alteration in the intra- and early postoperative endothelial function observed in open heart surgery.

Progressive myelopathy with hyperintensity on T2-weighted spinal MRI

The patient had a high titer of anti-human T lymphotrophic virus type-1 (HTLV-1) antibodies both in the plasma ( 262,144; normal < 16) and in the CSF ( 262,144; normal < 16), on the basis of which HTLV-1 -associated myelopathy (HAM) was diagnosed. Serum concentrations of vitamin B12 (243 pg/mL; normal: 233–914 pg/mL), folate (5.3 ng/mL; normal: 3.6–12.9 ng/mL), and angiotensin-converting enzyme 1 (13.2 U/L; normal: 7.7–29.4 U/ L) were normal. Spinal MRI in patients with HAM is characterized by thoracic cord atrophy without intensity changes and gadolinium enhancement. Recently, however, patients with HAM with high-signal-intensity areas on T2-weighted spinal MRI have been

Hot topic: Changes in angiotensin-converting enzyme inhibition and concentrations of the tripeptides Val-Pro-Pro and Ile-Pro-Pro during ripening of different Swiss cheese varieties

The angiotensin-converting enzyme (ACE) inhibitory activity and the concentration of the 2 ACE-inhibiting tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were studied during cheese ripening in 7 Swiss cheese varieties. The semi-hard cheeses Tilsiter, Appenzeller 1/4 fat, Tête de Moine, and Vacherin fribourgeois and the extra-hard and hard cheeses Berner Hobelkäse, Le Gruyère, and Emmentaler were investigated. Three loaves of each variety manufactured in different cheese factories were purchased at the beginning of commercial ripeness and investigated at constant intervals until the end of the usual sale period. Good agreement was found between ACE-inhibitory activity and the total concentration of VPP and IPP at advanced ripening stages. In most of the investigated varieties ACE-inhibitory activity and the concentration of the 2 tripeptides initially increased during the study period. A decline in the concentration of VPP and IPP was obtained toward the end of the investigated period for Tilsiter and Gruyère. The ratio of VPP/IPP decreased during ripening in all varieties with the exception of Emmentaler. However, large variations were observed among the cheese varieties as well as the individual loaves of the same variety. Chemical characterization of the investigated cheeses revealed that qualitative differences in the proteolysis pattern, not quantitative differences in the degree of proteolysis, are responsible for the observed variations in the concentrations of VPP and IPP. The presence of Lactobacillus helveticus in the starter culture was associated with elevated concentrations of VPP and IPP. The results of the present study show that concentrations of VPP and IPP above 100mg/kg are attainable in semi-hard cheese varieties after ripening periods of about 4 to 7 mo and that stable concentrations of the 2 antihypertensive tripeptides can be expected over several weeks of cheese ripening.

RNA interference targeting the ACE gene reduced blood pressure and improved myocardial remodelling in SHRs

The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar-Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37+/-3.90 ng/ml) compared with vehicle controls and vector controls (48.26+/-1.50 ng/ml and 46.67+/-2.82 ng/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (14.88+/-3.15 ng/ml; P>0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24+/-3.69 pg/ml) compared with vehicle controls and vector controls (46.21+/-5.06 pg/ml and 44.93+/-4.12 pg/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (16.06+/-3.11 pg/ml; P>0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P<0.05). ACE-RNAi treatment resulted in a reduction in systolic blood pressure by 22+/-3 mmHg and the ACE-RNAi-induced reduction lasted for more than 14 days. In contrast, blood pressure was continuously increased in the vehicle controls as well as in the vector controls. The ratios of heart weight/body weight and left ventricular weight/body weight were significantly lower in ACE-RNAi rats (3.12+/-0.23 mg/g and 2.24+/-0.19 mg/g) compared with the vehicle controls (4.29+/-0.24 mg/g and 3.21+/-0.13 mg/g; P<0.05) and the vector controls (4.43+/-0.19 mg/g and 3.13+/-0.12 mg/g; P<0.05). The conclusion of the present study is that ACE-silencing had significant antihypertensive effects and reversed hypertensive-induced cardiac hypertrophy in SHRs, and therefore RNAi might be a new strategy in controlling hypertension.