Is serum angiotensin converting enzyme level a useful non-invasive marker for liver fibrosis in patients with chronic hepatitis C?

Summary Objective: Chronic hepatitis C (CHC) continues to be a critical problem. The liver fibrosis score is the most valuable tool in determining treatment and prognosis. Liver biopsy is still considered a gold method but, due to unmet needs, new non-invasive markers are required. The aim of this study was to investigate any possible relationship between serum angiotensin-converting enzyme (ACE) levels and the stages of liver fibrosis in patients with CHC. Method: A total 100 CHC and 100 healthy subjects were enrolled in this study. The relationship between serum ACE level and the stages liver fibrosis was investigated using three different formats, as follows: (group [G]-I, classic Ishak's Score from F1 to F6; G-II, mild [F1-2], moderate [F3-4] and severe [F5-6]; G-III, mild [≤ F2] and advanced [F > 2]). The clinical usability of serum ACE level for both groups was also investigated. Results: Median serum ACE levels were higher in the healthy group than in CHC (42.5 [7-119] vs. 36 [7-91] U/I, p=0.002). There was no statistical difference among the three different fibrosis groups (G-I, G-II, G-III, p=0.797, p=0.986, and p=0.874) and no correlation between serum ACE level and the stages of liver fibrosis (r=0.026, p=0.923). The usability of serum ACE for evaluated patients with CHC and healthy subjects were calculated as 47% and 64%, respectively. Conclusion: Our study indicated that there is no relationship or correlation between serum ACE levels and stages of liver fibrosis in patients with CHC. The assessment of serum ACE level using genetically corrected reference values may provide more accurate results.

[Evaluation of serum angiotensin converting enzyme [ACE] activity in type 1 Gaucher's patient and its relationship to ACE gene insertion/deletion in intron 16]

Background: Gaucher's disease is an autosomal recessive disease which is the result of mutations in the P glucocerebrosidase gene. The aim of this study was to evaluate activity level of ACE enzyme Iranian patients with Gaucher's disease type I, and also polymorphism I/D in intron 16 of ACE gene, as a marker in diagnosis and monitoring of disease

Materials and methods: The experiments were performed on 29 patients [mean age of 10.04 years] and 60 healthy subjects [mean age of 7.31 years]. Procedures included DNA extraction from blood, detection of polymorphism I/D by PCR and evaluation of activity level of ACE enzyme

Results: The mean of ACE activity was 231.07 U/L which was increased 4 times than normal status [56.03 U/L]. Evaluation of polymorphism I/D of the 29 patients showed t6 [20.7%] II, 9 [31%] DD and 14[48.3%]ID[p<0.05]

Conclusion: According to the results, the measurement of the ACE activity levels can be used as cofactors in diagnosis and as well as an important factor in the monitoring of treatment. Polymorphism I/D with respect to the role of the ACE activity can be effective in increasing the specificity of the experiments

Determination of angiotensin I-converting enzyme activity in equine blood: lack of agreement between methods of analysis

Angiotensin-I converting enzyme (ACE) is a key regulator of blood pressure, electrolytes and fluid homeostasis through conversion of angiotensin I into angiotensin II. Recently, a genetic polymorphism of the ACE gene, which accounts for 47% of the variation of ACE activity in blood, has been advocated as a biomarker of athletic aptitude. Different methods of analysis and determination of ACE activity in plasma have been used in human and equine research without a consensus of a "gold standard" method. Different methods have often been used interchangeably or cited as being comparable in the existing literature; however, the actual agreement between assays has not been investigated. Therefore, in this study, we evaluated the level of agreement between three different assays using equine plasma obtained from 29 horses. Two spectrophotometric assays using Furylacryloyl-phenylalanyl-glycyl-glycine as substrate and one fluorimetric assay utilizing o-aminobenzoic acid-FRK-(Dnp)P-OH were employed. The results revealed that the measurements from the different assays were not in agreement, indicating that the methods should not be used interchangeably for measurement of equine ACE activity. Rather, a single method of analysis should be adopted to achieve comparable results and critical appraisal of the literature is needed when attempting to compare results obtained from different assays.

Null genetic risk of ACE gene polymorphisms with nephropathy in type 1 diabetes among Egyptian population

Reported to date, strong evidence exists in multiple studies for genetic predisposing in the development of diabetic nephropathy, and no studies addressed this issue among Egyptian population. The results of angiotensin converting enzyme gene [ACE] in the susceptibility to nephropathy in type 1 diabetes with nephropathy are conflicting. We aim to identify the associations of two ACE gene polymorphisms [PstI, A > G substitution and a 287-bp insertion/deletion] with nephropathy in type 1 diabetes in Egyptian children/adolescents. Our case-control study contained 140 diabetic individuals; 80 diabetic with nephropathy as cases, and 60 diabetic subjects without nephropathy as control group. Amplified DNA from peripheral leucocytes/buccal mucosa was genotyped for using polymerase chain reaction and enzymatic assay. We found no significant differences in the distribution of ACE insertion/deletion and PstI genotypes or allele frequencies were observed between the examined groups. Frequencies of PstI-indel haplotypes were similar in all of our study groups. In both cases and control subjects, ACE activity and microalbuminuria were highest among D/D homozygotes and lowest in I/I homozygotes, while a dissimilar result was seen in PstI polymorphism. Our findings in Egyptian population strongly conclude that there is no association between the ACE gene I/D and PstI polymorphisms with nephropathy in type 1 diabetes

Crisis epiléptica como primera manifestación de sarcoidosis: caso clínico / Sarcoidosis presenting as partial seizures: report of one case

The nervous system is affected in 10 percent of patients with sarcoidosis. However, neurological disturbances are rarely the frst manifestation of the disease. We report a 36-year-old woman presenting with partial seizures that generalized secondarily. Magnetic resonance showed a left parietal cortical-subcortical lesion with a minimal mass effect, moderate vasogenic edema and intense enhancement with intravenous contrast. A magnetic resonance spectroscopy disclosed a low aggressiveness profle, compatible with an infammatory lesion. Angiotensin converting enzyme levels were normal. The lesion was excised and the pathological study showed the presence of granulomas with dubious necrosis. The patient was treated with antituberculous drugs. One year later, the lesion had grown and a thorax CT scan showed numerous mediastinal and hilar lymphadenopathies. A new determination of angiotensin converting enzyme disclosed elevated levels and the biopsy of mediastinal lymph nodes confrmed the presence of sarcoidosis.

Silica exposure and serum angiotensin converting enzyme activity

Silicosis is known in industrial workers for centuries. Till recently, the mainstay of its diagnosis and progress was clinical examination of the respiratory system, pulmonary function test and chest radiography. Several biomarkers such as serum angiotensin converting enzyme [ACE] activity have been examined to determine the extent of silicosis. To elucidate the effect of age, gender, duration of exposure to silica dust, smoking habit, and pulmonary function status on the serum ACE activity among quartz stone workers without disease. A cross-sectional study was carried out on 134 [111 men and 14 women] workers of quartz stone crushing units were studied. Standard diagnostic criteria were used for diagnosing silicosis and tuberculosis. Pulmonary functions of the participants were also assessed. The mean +/- SD age for participants was 26.1 +/- 6.3 years [26.6 +/- 6.3 for men and 21.9 +/- 4.3 for women]. The mean +/- SD duration of exposure was 1.1 +/- 1, 9 years. In the present study, only one case of silicosis and eight cases of tuberculosis were found. The mean +/- SD serum ACE levels for those with and without respiratory disease were 68.44 +/- 11.61, and 66.9 +/- 14.4 IU/L, respectively [p>0.05]. We could not observe any association between serum ACE activity and age, gender, duration of exposure, smoking habits and pulmonary function status. However, elevated levels of serum ACE was found in a solitary case of silicosis

Diferenças entre os sexos na atividade da enzima conversora de angiotensina e na pressão arterial em crianças: um estudo observacional / Gender differences in serum angiotensin-converting enzyme activity and blood pressure in children: an observational study

FUNDAMENTO: A enzima conversora da angiotensina (ECA), principal enzima do sistema renina-angiotensina (SRA), desempenha um papel importante na regulação da pressão arterial. A atividade enzimática da ECA e sua relação com a pressão arterial (PA) durante a infância e a adolescência ainda não foram claramente estabelecidas. OBJETIVO: Determinar as diferenças relacionadas ao sexo nos níveis séricos da ECA e nas alterações da PA, bem como a relação entre ECA e PA, em estudantes entre 8 e 18 anos de idade. MÉTODOS: Os valores de pressão arterial, peso, altura, índice de massa corporal (IMC) e níveis séricos da ECA foram medidos em 501 crianças. RESULTADOS: Os valores médios da ECA foram mais elevados em meninos (143,7 ± 57,1) do que em meninas (130,2 ± 54,9) (p = 0,004). Enquanto nas meninas os níveis séricos da ECA diminuíram com a idade, nos meninos ocorria o inverso. Após o início da puberdade, os níveis da ECA eram mais elevados em meninas do que em meninos da mesma idade. Nos dois sexos, a idade foi um forte determinante da pressão arterial (PA). Constatamos a existência de uma relação entre a ECA e a pressão arterial sistólica (PAS) e a pressão arterial diastólica (PAD) nas meninas (PAS: r = -0,20; p < 0,001; PAD: r = 0,12; p < 0,03). O índice de massa corporal (IMC) apresentou uma correlação maior com a PAS e a PAD nas meninas (r = 0,37 e 0,31 respectivamente; p < 0,001) do que nos meninos ( r = 0,26 e 0,25 respectivamente; p < 0,001). CONCLUSÃO: Esses resultados indicam que houve diferenças na atividade da ECA entre os meninos e meninas deste estudo. Nas meninas, os níveis séricos da ECA eram mais baixos e diminuíram com a idade, enquanto a PA aumentou. Como ocorre um dimorfismo sexual na PA durante a puberdade, nossos achados indicam que os hormônios gonadais podem afetar a atividade da ECA e a PA. Esses resultados podem ter importantes implicações terapêuticas.

BACKGROUND: Angiotensin-converting enzyme (ACE) is a key enzyme of the renin-angiotensin system that plays an important role in regulating blood pressure. ACE enzyme activity and its relationships with blood pressure (BP) during childhood and adolescence have not yet been clearly established. OBJECTIVE: To determine serum ACE (S-ACE) levels and BP changes in school children between 8 and 18 years of age and how S-ACE and BP in males and females might differ, as well as to determine S-ACE and BP relationships. METHODS: Blood pressure, height, weight, body mass index (BMI), and S-ACE were measured in 501 children. RESULT: Mean S-ACE values were higher in boys (143.7±57.1) than in girls (130.2 ± 54.9) (p = 0.004). S-ACE values decreased in girls and increased in boys with age, and values for girls were lower than for age-matched boys after onset of puberty. Age was a strong determinant of BP levels in both genders. We found a relationship between ACE and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in girls (SBP r= -0.20 p<0.001 DBP r=0.12 p<0.03). BMI had greater correlation with SBP and DBP in girls (r=0.37, and 0.31, respectively; p < 0.001) than in boys (r=0.26, and 0.25 respectively; p<0.001). CONCLUSION: These results indicate that gender differences in serum ACE activity exist in the children from this study. This activity was lower and decreased with age in girls, while BP increased. Because sexual dimorphism in BP emerges in puberty, our findings suggest that gonadal hormones might affect S-ACE activity and BP. These results may have important therapeutic implications.

Enzima conversora de angiotensina no líquido pericárdico: estudo comparativo com a atividade sérica / Angiotensin-converting enzyme in pericardial fluid: comparative study with serum activity

FUNDAMENTO: A caracterização de uma enzima conversora de angiotensina (ECA) no líquido pericárdico humano é relevante diante do seu papel na liberação de angiotensina II e, portanto, do papel do pericárdio na homeostase cardivascular. OBJETIVO: Isolar e caracterizar uma ECA do líquido pericárdico humano. Comparar as atividades conversoras de angiotensina I do fluido pericárdico e do soro de pacientes submetidos à cirurgia cardiovascular. MÉTODOS: A enzima do líquido pericárdico humano foi purificada por meio de etapas cromatográficas e caracterizada por eletroforese em gel de poliacrilamida (SDS-PAGE), hidrólise de angiotensina I, bradicinina, Hip-His-Leu e substratos sintéticos com supressão interna de fluorescência. Lisinopril foi usado como inibidor. A atividade de ECA foi determinada em amostras de sangue e líquido pericárdico de 23 pacientes submetidos à cirurgia cardiovascular. RESULTADOS: A ECA purificada (MM = 140 kDa) libera angiotensina II, hidrolisa a bradicinina e o substrato Hip-His-Leu. Os parâmetros cinéticos k cat,(s-1) e k cat/Km (µM-1. s-1) foram respectivamente: Hip-His-Leu (1,14 e 7 x 10 -4), Abz-YRK(Dnp)P-OH (2,60 e 0,77), Abz-LFK(Dnp)-OH (2,77 e 0,36) e Abz-SDK(Dnp)P-OH (1,92 e 0,19). As atividades conversoras de angiotensina I (média ± DP) do líquido pericárdico e no soro foram, respectivamente, 3,16 ± 0,90 mU x mg -1x min-1 e 0,33 ± 0,11 mU x mg -1x min-1 . A diferença foi significativa entre os dois fluidos. CONCLUSÃO: Uma ECA com grande similaridade com a enzima somática foi isolada do fluido pericárdico humano. A atividade conversora de angiotensina I é maior no líquido pericárdico quando comparada com a atividade do soro. Esses dados constituem importante evidência do papel do líquido pericárdico no metabolismo de peptídeos ativos.

BACKGROUND: The characterization of an angiotensin-converting enzyme (ACE) in human pericardial fluid is relevant, considering its role in the angiotensin II release and thus, the role of the pericardium in cardiovascular homeostasis. OBJECTIVE: To isolate and characterize an ACE from human pericardial fluid and to compare the angiotensin I converting activities of the pericardial fluid with that of the serum in patients submitted to cardiovascular surgery. METHODS: The enzyme from human pericardial fluid was purified through chromatographic steps and characterized by polyacrylamide gel electrophoresis (SDS-PAGE), hydrolysis of angiotensin I, bradykinin, Hip-His-Leu and synthetic substrates with internal fluorescence suppression. Lisinopril was used as inhibitor. The ACE activity was measured in blood and pericardial fluid samples of 23 patients submitted to cardiovascular surgery. RESULTS: The purified ACE (MM = 140 kDa), releases angiotensin II, hydrolyses bradykinin and the Hip-His-Leu substrate. The kinetic parameters k cat,(s-1) and k cat/Km (µM-1. s-1) were, respectively: Hip-His-Leu (1.14 and 7 x 10 -4) ; Abz-YRK(Dnp)P-OH (2.60 and 0.77), Abz-LFK(Dnp)-OH (2.77 and 0.36) and Abz-SDK(Dnp)P-OH (1.92 and 0.19). The angiotensin I converting activities (mean ± SD) in the pericardial fluid and in blood, were, respectively: 3.16 ± 0.90 mU x mg -1x min-1 and 0.33 ± 0.11 mU x mg -1x min-1. The difference was significant between the two fluids. CONCLUSION: An ACE that bears great similarity with the somatic enzyme was isolated from human pericardial fluid. The angiotensin I converting activity is higher in the pericardial fluid when compared to the serum activity. These data are important evidence of the role of the pericardial fluid in the metabolism of active peptides.

Mayor expresión de la enzima convertidora de angiotensina I homóloga (ECA2) en la pared arterial de ratas con niveles genéticamente elevados de angiotensina II: efectos decandesartán y fasudil / Increased expression of homologous Angiotensin I converting enzyme (ACE2) in the arterial wall of rats with genetically elevated levels of Angiotensin II: effects of candesartan and fasudil

El polimorfismo de la enzima convertidora de angiotensina I (ECA) determina mayor actividad de ECA y niveles de angiotensina (Ang) II en ratas Brown Norway (BN) y menor actividad de ECA y niveles de Ang II en ratas Lewis (L). La relación entre ECA, ECA2, la estimulación del receptor de angiotensina (Ang) II y la vía transduccional Rho A/Rho kinasa no ha sido explorada. Objetivo: Determinar la actividad y expresión de ECA2 y eNOS en la aorta de ratas con niveles genéticamente elevados de ECA y Ang II y los efectos independientes de la inhibición del receptor de Ang II (RAT1) y de Rho kinasa (ROCK). Métodos: Se usaron ratas macho homocigotos de 150 grs BN y L. Para inhibir ROCK, se administró fasudil (100 mg/Kg/día por gavage) y para inhibir el RAT1 se administró candesartán (10 mg/kg/día por gavage) a ratas BN, durante 7 días. Se determinó la presión arterial sistólica (PAS), la actividad circulante de ECA y ECA2 por fluorimetría y la expresión génica de ECA2 y de eNOS por RT-PCR (en unidades de densidad óptica).Resultados como promedio(ES). Conclusión: Los mayores niveles de ECA y AngII están asociados a menor actividad circulante de ECA2 en ratas normotensas. Candesartán y fasudil aumentaron la actividad y expresión génica de ECA2 en la pared arterial de ratas BN, efecto que fue mayor al inhibir ROCK. El aumento de ECA2 se asoció a mayor expresión génica de eNOS independientemente de la vía inhibida. Estos resultados permiten plantear que óxido nítrico y ROCK pudieran ser activadores endógenos de ECA2.

Background: Angiotensin I converting enzyme (ACE) polymorphism is associated with increased ACE activity and angiotensin II (A-II) levels in Brown Norway (BN) rats and decreased ACE and A-II levels in Lewis (L) rats. The relationship of ACE, ACE 2, stimulation of A-II receptor and activity of the Rho A/ Rho kinase transductional pathway is not known. Aim: To determine the activity and expression of ACE 2 and eNOS in the aortic wall of rats with genetically elevated leves of ACE and A-II and the independent effects of A-II receptor (ART2) and Rho kinase (ROCK) inhibition. Methods: Homozygous BN and L male rats wighing 150g were used. Fasudil (100mg/kg/day via gavage) was administer to inhibit ROCK and candesartan (10 mg/Kg/day) was given to inhibit ART1, during 7 days. Systolic blood pressure (SBP, ACE and ACE2 circulating activity was measured by fluorimetry. Genetic expression of ACE2 and eNOS was determined by RT-PCR (optical density units). Results are expressed as mean +/- SEM.

Polymorphism in the angiotensin-converting enzyme [ACE] gene and ACE activity in type 2 diabetic patients

It has recently been shown that an insertion [I]/deletion [D] polymorphism exists in the angiotensin-converting enzyme [ACE] gene that can affect the serum ACE level. There are three genotypes: DD, DI, and II, with the ACE level being highest in DD, intermediate in DI, and lowest in II. The DD genotype has been reported as a genetic risk factor for diabetes mellitus. In the present investigation, 170 patients with type 2 diabetes mellitus [T2DM] and 144 control subjects were studied. The ACE I/D polymorphism was determined by polymerase chain reaction [PCR] utilizing specific primers. ACE activity was determined spectrophotometrically. Distribution of ACE gene [I/D] polymorphism and allele frequencies in patients with T2DM were significantly different from those in control [P < 0.001]; D allele frequency was 51% in T2DM vs. 48% in controls. The level of ACE activity was significantly higher in the DD genotype [91.1 +/- 23.18] than those in ID [60.6 +/- 22.8] and in II genotypes [36.8 +/- 6.9]. There was a significant difference in genotype distribution between the two groups [P < 0.001]. New normal ranges of serum ACE level were determined for each genotype. Moreover, we found test sensitivity to be 62.3%. Serum ACE activity was significantly associated with ACE [I/D] gene polymorphism

Insertion/deletion gene polymorphism and serum level of angiotensin converting enzyme

Angiotensin converting enzyme [ACE] plays an important role in cardiovascular regulation. Since the initial report regarding the association of insertion/deletion gene polymorphism and serum concentration of ACE, there have been investigations in different populations with contradicting results. The aim of this study was to assess the association of the ACE polymorphism and serum level in Iranians.The study recruited 88 healthy individuals [70 males and 18 females; mean age: 30.07 yrs.] who were candidates for kidney donation. To investigate the association of ACE serum level and polymorphism, the serum concentration of ACE was measured spectrophotometrically and ACE genotyping was determined by polymerase chain reaction.The genotype distribution of DD, ID and II was 31, 24 and 33 respectively. The mean ACE serum concentration for DD, ID and II genotypes was 50.68, 36.65 and 32.06 IU/L, respectively. There was a significant difference in ACE serum level among the three genotypes [p < 0.05]. While the highest ACE serum concentration was seen in DD group [nearly 1.5 times of that of ID and II genotypes, respectively], it was the lowest in the II group. Our study showed that insertion/deletion polymorphism of ACE gene was strongly associated with plasma ACE levels in the Iranian population

Cutaneous sarcoidosis: clinical profile of 23 Indian patients.

BACKGROUND: Sarcoidosis is a multisystem disease of undetermined etiology. Indian studies on cutaneous sarcoidosis are not many and mainly comprise case reports. AIMS: This retrospective study was carried out to assess the clinical profile of sarcoidosis patients presenting with cutaneous lesions. METHODS: All histopathologically proven cases of cutaneous sarcoidosis seen consecutively between 1999 and 2004 were studied. Their age, sex, presenting features, evolution of disease and laboratory parameters were analyzed. RESULTS: A total of 23 patients (F:M 15:8) between 31 to 78 years (mean 44.3 years) of age had the mean duration of skin lesions of 1.4 years. Six patients had one to four lesions; two patients each had scar sarcoidosis and angiolupoid and one patient each had recurrent erythema nodosum, leg lymphedema and subcutaneous sarcoidosis. Others showed combination of papules, nodules, plaques and psoriasiform lesions. Peripheral lymph nodes were involved in two patients. Among 10 patients of pulmonary involvement, three had become symptomatic four months to four years after the cutaneous lesions. Routine laboratory investigations including serum calcium estimation were normal in all cases. Serum angiotensin-converting enzyme levels were raised in 3 out of 6 patients. Asymptomatic lytic lesions of digital bones were detected in hand X-ray of one patient. CONCLUSION: Skin lesions of sarcoidosis are like the tip of an iceberg indicating more changes in other organs. The symptomatology and abnormal laboratory results do not necessarily correlate with the severity of cutaneous involvement in general.

Angiotensin converting enzyme gene polymorphism in Indian children with steroid sensitive nephrotic syndrome.

CONTEXT: Nephrotic syndrome is one of the commonest renal problem encountered in children. It is difficult to predict at onset, the clinical course in terms of steroid responsiveness or resistance. Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical course in common multi-factorial diseases including focal segmental glomerulosclerosis. There is no study available from our country till date to find out any correlation of the steroid response in idiopathic nephrotic syndrome and ACE gene polymorphism. AIM: To study distribution and correlation of ACE gene I/D polymorphism in idiopathic steroid sensitive nephrotic syndrome. SETTINGS & DESIGN: Case-control retrospective study. SUBJECTS & METHODS: We studied ACE gene polymorphism in 90 consecutive patients (82% males, 18% females) with steroid sensitive idiopathic nephrotic syndrome and 300 normal controls (NC). STATISTICAL ANALYSIS: Chi-square test and Fisher's exact test (for cases with insufficient expected cell frequencies). RESULTS: The mean age of onset was 5.3 +/- 4 years. Steroid sensitive (SS) patients showed II (SS-48%, NC-26%) genotype was more frequent than normal controls (p=0.002). There was no significant difference in genotype frequencies among steroid SS subgroups. CONCLUSIONS: In our study II genotype was more frequent in steroid sensitive nephrotic syndrome children in comparison to normal controls. Further functional studies with large number of children are required to investigate the role of II genotype in steroid sensitive nephrotic syndrome. Comparison of the genotypic frequency with steroid resistant patients may provide information, which might be useful in clinical practice.

A continuous fluorescent assay for the determination of plasma and tissue angiotensin I-converting enzyme activity

A continuous assay using internally quenched fluorescent peptides with the general sequence Abz-peptidyl-(Dnp)P-OH (Abz = ortho-aminobenzoic acid; Dnp = 2,4-dinitrophenyl) was optimized for the measurement of angiotensin I-converting enzyme (ACE) in human plasma and rat tissues. Abz-FRK(Dnp)P-OH, which was cleaved at the Arg-Lys bond by ACE, was used for the enzyme evaluation in human plasma. Enzymatic activity was monitored by continuous recording of the fluorescence (lambdaex = 320 nm and lambdaem = 420 nm) at 37°C, in 0.1 M Tris-HCl buffer, pH 7.0, with 50 mM NaCl and 10 æM ZnCl2. The assays can be performed directly in the cuvette of the fluorimeter and the hydrolysis followed for 5 to 10 min. ACE measurements in the plasma of 80 healthy patients with Hip-His-Leu and with Abz-FRK(Dnp)P-OH correlated closely (r = 0.90, P < 0.001). The specificity of the assay was demonstrated by the complete inhibition of hydrolysis by 0.5 æM lisinopril or captopril. Abz-FRK(Dnp)P-OH cleavage by ACE was monitored in rat lung, kidney, heart, and liver homogenates in the presence of a cocktail of inhibitors containing trans-epoxy-succinyl-L-leucylamido-(4-guanido)-butene, pepstatin, phenyl-methylsulfonyl fluoride, N-tosyl-L-phenylalanyl-chloromethyl ketone, and N-tosyl-lysyl-chloromethyl ketone to prevent undesirable hydrolysis. ACE activity in lung, heart and kidney homogenates, but not in liver homogenates, was completely abolished by 0.5 æM lisinopril or captopril. The advantages of the method are the procedural simplicity and the high sensitivity providing a rapid assay for ACE determinations.

Association study of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with myocardial infarction

The angiotensin converting enzyme (ACE) is a strong candidate gene for myocardial infarction (MI). Insertion-deletion dimorphism in intron 16 of this gene has been inconclusively found to be associated with it. Several new polymorphisms in the ACE gene have been identified and among these, a dimorphism in exon 17, ACE G2350A, has a significant effect on plasma ACE concentrations. To assess the value of genotyping the ACE G2350A dimorphism in a genetically homogeneous population, we carried out a case-control study of dimorphism G2350A for a putative association with MI among Pakistani nationals. We investigated a sample population of 370 Pakistanis, comprising 163 controls, and 207 patients with clinical diagnosis of acute MI (AMI). ACE G2350A alleles were visualized by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of G alleles were 0.68 among controls and 0.72 among AMI patients. The ACE G2350A dimorphism showed no significant association with MI (c2=0.90, 2 df, P=0.64), plasma levels of homocysteine (P=0.52) or with serum levels of folate (P=0.299). The results indicate that ACE G2350A polymorphism is not associated with risk of myocardial infarction in the Pakistani population investigated here.

Anglotensin converting enzyme activity as a marker of hepatocellular carcinoma

Our study have pointed to the change of serum angiotensin-converting enzyme [SACE] values in patients with liver disease and cancer located at different sites. The aim of this study was to determine the change in SACE values in patients with hepatocellular carcinoma [HCC] and liver cirrhosis. The study comprised 20 patients with HCC and 20 patients with liver cirrhosis. The control group consisted of 10 healthy volunteers. Liver function tests, abdominal ultrasonography and liver biopsy for diagnosis and grading the cases of liver cirrhosis and HCC. Serum alpha-fetoprotein [AFP] was measured by radioimmunoassay and SACE was measured by colorimetric method. The mean SACE value was considerably significantly lower in patients with HCC when compared to those with liver cirrhosis and control groups. The mean value of SACE was significantly correlated with the degree of differentiation of the tumor. In patients with liver cirrhosis, SACE value was significantly increased when compared to HCC and control group. It was found that there was a negative correlation between AFP value and SACE value. The study has shown that SACE values are low in patients with advanced HCC and high in patients with liver cirrhosis. Using a cut-off point for ACE 3.8 U/L in patients with HCC yielding sensitivity and specificity 93.3% and 100% respectively. While using a cut-off point for AFP 200 ng/nil yielding sensitivity and specificity 56.7% and 100% respectively. It may be helpful in detecting HCC in patients with liver cirrhosis, where it can be difficult to differentiate between small HCC and regenerating nodules

Sarcoidosis in Turkey: 1954 - 2000

Sarcoidosis is a multisystemic disease of unknown etiology. The presentation and frequency of different organ involvement can vary according to race, geographical location and gender. Because of the multiorgan involvement and its mimicking nature, the diagnosis is usually a challenge, even to specialists. Therefore, knowledge of the epidemiologic features of the disease is important. The first case report of sarcoidosis in Turkey was published in 1954. We obtained data from case series by hand searching of journals and congress abstract books on pulmonary medicine between 1954 and 2000. Series of 5 or more cases were included in our compilation of data. Data for 1327 patients with the diagnosis of sarcoidosis were obtained from 29 reports. There were nearly twice as many females as males with the disease in these case series. Most of the patients were at stage 1 or 2 at the time of diagnosis. Peripheral lymph node enlargement was reported in 119 patients, skin involvement in 22 and nervous system involvement in 12 patients. Erythema nodosum was reported in 137 patients. Serum angiotensin-converting enzyme was elevated in 52% and the tuberculin skin test was positive in 24% of patients. Organ biopsies seemed to be the preferred diagnostic method in the initial papers while recent papers revealed the value of obtaining a bronchoscopic biopsy.Despite several limitations of our study, this is the first compilation of 46 years of data on sarcoidosis in Turkey. Further studies on the geographical distribution and incidence and prevalence are needed for our country

Angiotensin converting enzyme gene polym orphism in Korean patients with primary knee osteoarthritis

Angiotensin converting enzyme (ACE) plays an important role in the physiology of vasculature, blood pressure and inflammation. ACE gene, known to have insertion/deletion (I/D) polymorphism, has been widely investigated in its relation with cardiovascular and neurodegenerative diseases and longevity. ACE gene polymorphism in an inflammation associated osteoarthritis (OA) patients is not known. Here we have investigated ACE gene polymorphism in 142 Korean primary knee OA patients and 135 healthy volunteers to establish any clinical correlates between ACE polymorphism and knee osteoarthritis. Clinical parameters such as disease onset age, Kellgren-Lawrence grade and Lequesne's functional index provided additional analysis of the relationship of ACE polymorphism and clinical features of OA. Early onset OA showed significantly higher allele frequency and carriage rate of I than late onset OA. Radiographically severe and functionally poor OA showed higher carriage rate of I allele than radiographically mild and functionally good OA, respectively. This study first reports ACE gene polymorphism to be a risk factor for early onset, severe form primary knee OA.

Evaluation of serum angiotensin converting enzyme [SACE] as a diagnostic marker for pulmonary embolism

A number of supportive laboratory tests such as ECG, Chest x-ray, ABGs, SLDH, SGOT, S. Bilirubin and D-dimer with variable sensitivity and specificity are available to facilitate the clinical diagnosis of acute Pulmonary Embolism [PE]. Serum Angiotensin Converting Enzyme [SACE] which is produced mainly by the pulmonary vascular endothelial cells, is found altered during a variety of diffuse lung diseases. This study was designed to evaluate the validity of SACE level as a marker for hypoxic damage to the pulmonary endothelium in PE. Design: A prospective study carried out on forty patients with high clinical suspicion of PE. Besides routine diagnostic tests mentioned above all of them had Ventilation Perfusion isotope [V/Q] scans [as a diagnostic test] and SACE level checked. Setting: Shaikh Zayed Hospital Lahore. Results. Among forty consecutive patients with age range 25-59 years [mean: 42 Yr], twenty six patients [65%] with abnormal scans reported as High Probability' were included in group-A [True Positive], whereas 14[35%] patients having Low-Probability [Suspected] or Normal scan were included in group-B, Low SACE level [<28iu/L] was found in 19/26 [sensitivity of 73%] in Group-A [Positive Predictive Value: 47%] and 9/14 [sensitivity of 64%] in Group-B, whereas mean levels for both groups were 34.55 and 54.84 respectively. Rise in LDH was pronounced in Group-A. Only chest X-ray and ECGs were found to be more sensitive for group-A than group-B. Changes in ABGs [Type-1 Resp. Failure] had low sensitivity. Among clinically suspected cases of PE, fall in SACE level can be used as a sensitive and reliable diagnostic marker as more than 75% of the enzyme is produced in the lungs compared with other enzymes which have extra-pulmonary source

Standardization of a fluorimetric assay for the determination of tissue angiotensin-converting enzyme activity in rats

The tripeptide Hip-His-Leu was used to standardize a fluorimetric method to measure tissue angiotensin-converting enzyme (ACE) activity in rats. The fluorescence of the o-phthaldialdehyde-His-Leu adduct was compared in the presence and absence of the homogenate (25 µl) to determine whether the homogenate from different tissues interfered with the fluorimetric determination of the His-Leu product. Only homogenates from lung and renal medulla and cortex showed significantly altered fluorescence intensity. To overcome this problem, the homogenate from these tissues were diluted 10 times with assay buffer. The specificity of the assay was demonstrated by the inhibition of ACE activity with 3 µM enalaprilat (MK-422). There was a linear relationship between product formation and incubation time for up to 90 min for homogenates of renal cortex and medulla and liver, for up to 60 min for ventricles and adrenals and for up to 30 min for the aorta, lung and atrium homogenates. In addition, there was a linear relationship between product formation and the amount of protein in the homogenates within the following range: lung, 30-600 µg; renal cortex and medulla, 40-400 µg; atrium and ventricles, 20-200 µg; adrenal, 20-100 µg; aorta, 5-100 µg; liver, 5-25 µg. No peptidase activity against the His-Leu product (31 nmol), assayed in borate buffer (BB), was detected in the different homogenates except the liver homogenate, which was inhibited by 0.1 mM r-chloromercuribenzoic acid. ACE activity in BB was higher than in phosphate buffer (PB) due, at least in part, to a greater hydrolysis of the His-Leu product in PB. ACE activity of lung increased 20 percent when BB plus Triton was used. Enzyme activity was stable when the homogenates were stored at -20o or -70oC for at least 30 days. These results indicate a condition whereby ACE activity can be easily and efficiently assayed in rat tissue samples homogenized in BB using a fluorimetric method with Hip-His-Leu as a substrate.