Beta Elemene induces cytotoxic effects in FLT3 ITD-mutated acute myeloid leukemia by modulating apoptosis.

OBJECTIVE: ß-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether ß-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how ß-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: ß-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that ß-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. ß-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that ß-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.

Association of single nucleotide polymorphisms in CXCR1, CXCR2 and CXCL5 with Behçet disease: a study in the Denizli province of Turkey.

BACKGROUND: Behçet disease (BD) is associated with the immune system, especially neutrophilic activity. The CXCR1, CXCR2 and CXCL5 genes mediate the activation and migration of neutrophils. AIM: To investigate CXCR1, CXCR2 and CXCL5 single nucleotide polymorphisms (SNPs) and examine their association with BD. METHODS: We studied polymorphic sites in CXCR1 (four sites: rs16858811, rs9282752, rs16858809 and rs16858808), CXCR2 (three sites: rs2230054, rs1126579 and rs1126580) and CXCL5 (one site: rs352046) in 87 patients with BD and 111 healthy controls (HCs), using a PCR restriction-fragment length polymorphism-based approach for genotyping. RESULTS: We found that the CXCR2 rs2230054 TT genotype and the CXCL5 rs352046 polymorphism might be possible genetic factors responsible for BD. We did not find any association between the development of BD and any of the four CXCR1 polymorphisms or the other two CXCR2 SNPs. In addition, our haplotype analysis results indicated that the haplotypes of the CXCR2 and CXCR1-CXCR2 polymorphic loci were different between the BD and HC groups. CONCLUSION: Our study suggests that polymorphisms of CXCR1, CXCR2 and CXCL5 may affect susceptibility to BD and increase the risk of developing the disease. These loci need to be studied in larger groups of patients from different geographical areas around the world in order to clarify the genetic background for BD pathogenesis.

Genetic origin of Behçet's disease population in Denizli, Turkey; population genetics data analysis; historical demography and geographical perspectives based on ß-globin gene cluster haplotype variation.

In our study, we aimed to investigate the possible genetic drift, relationships, expansion and historical origin based on haplotype frequencies of the ß-globin gene cluster of normal and Behçet's disease (BD) population in Denizli, Turkey. We examined blood DNA samples obtained from our DNA bank. The association of population genetic parameters such as haplotypes, diversity, differentiation, Hardy-Weinberg equilibrium and demographic analysis for two populations was performed by Arlequin ver. 3.5. Our results show that both populations have high similarity in genetic parameters in terms of development and expansion based on haplotype diversity through the history. We found that historical levels of gene flow were significantly higher between the two populations. According to historical population, growth parameter of τ values for normal and BD populations dated approximately 42 000 to 38 000 ybp, respectively. In conclusion, historically, two populations show similar genetic parameters and unimodal growth distribution. Our results are consistent with the view that the BD may have occurred in area, independent from Silk Road.

Exercise and suspension hypokinesia-induced alterations in mechanical properties of rat fast and slow-twitch skeletal muscles.

Physical activity has a modulatory role on regulatory steps of excitation-contraction coupling (ECC) determining skeletal muscle contractility. We evaluated and compared the contractile responsiveness and caffeine-induced contractures of fast (extensor digitorum longus; EDL) and slow-twitch (soleus; SOL) muscles in suspension hypokinesia (SH) and exercised rats. After SH or low intensity exercise, EDL and SOL were isolated, twitch and tetanic contractions and caffeine (10 mM) contractures were recorded. Twitch and tetanic contractions of EDL increased by 60% in exercised rats (p <0.05) while no alteration was observed after SH. Exercise did not alter twitch and tetanic contractions of SOL, while SH depressed contractions (p <0.05). Caffeine contractures were diminished in exercised rat EDL (P <0.05). In SH-rat EDL, contractures increased in amplitude (p <0.01) with a rapid time course (p <0.05). Contractures did not change in SOL after exercise or SH. We concluded that SH and exercise exerted diverse modulatory effects on skeletal muscle contractility. Contractile improvement due to exercise was prominent in EDL. Our results suggest that the muscle-type specific adaptations are related to a change in ECC due to the differences in the regulatory steps, particularly in the intracellular Ca(2+) handling mechanisms.

Role of activated protein C on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis induced by cecal ligation and puncture: an experimental study in the rat.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. The delaying effects of intra-abdominal sepsis on wound healing process in colonic anastomoses have been previously demonstrated. This study was designed to investigate the role of APC on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. METHODS: The left colonic anastomosis was performed in 48 rats that were divided into four groups: (1) sham-operated group, laparatomy plus cecal mobilization (n = 12); (2) sham + APC group, identical to group I except for APC treatment (n = 12); (3) CLP group, cecal ligation and puncture (n = 12); 4) CLP + APC-treated group, 100 microg/kg, 15 min before the construction of colonic anastomosis (n = 12). Anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), and nitrate/nitrite (NO3(-) /NO2(-)) levels. The plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and D-dimer also were measured. RESULTS: Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures and tissue HP contents, along with increases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). However, APC treatment led to significant increases in anastomotic bursting pressures and tissue HP ontents, along with decreases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). CONCLUSIONS: This study clearly showed that APC treatment prevented the delaying effects of intra-abdominal sepsis on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of anastomotic healing during particular surgeries in which sepsis-induced injury occurs.

Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion. MATERIALS AND METHODS: Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk. RESULTS: Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05). CONCLUSIONS: This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

Splenic hydatid cyst perforating into the colon manifesting as acute massive lower gastrointestinal bleeding: an unusual presentation of disseminated abdominal echinococcosis.

Hydatid disease can occur in all viscera and soft tissues, although the liver and the lungs are the organs most commonly involved. Isolated splenic involvement with the disease is extremely rare. Splenic hydatid cysts may suppurate, fistulise to adjacent organs, or rupture into the peritonaeal cavity. However, acute, massive lower gastrointestinal bleeding due to splenocolic communication resulting from splenic echinococcal cyst has not been previously reported. We present a 77-year-old woman with disseminated abdominal echinococcosis, and active lower gastrointestinal bleeding due to splenocolic fistula resulting from splenic hydatid cyst. She was treated successfully with en-bloc excision of the spleen and splenic flexure of the colon.

Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process. METHODS: Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 microg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 microg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured. RESULTS: Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). CONCLUSION: This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.

Activated protein C attenuates intestinal reperfusion-induced acute lung injury: an experimental study in a rat model.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. APC has been shown to attenuate local deleterious effects of ischemia/reperfusion (I/R) injury in many organs. We aimed to investigate the effects of APC on lung reperfusion injury induced by superior mesenteric occlusion. METHODS: Male Wistar-Albino rats were allocated into 4 groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to group 1 except for APC treatment (n = 12); (3) intestinal I/R group, 60 minutes of ischemia followed by 3 hours of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 microg/kg injection of APC intravenously, 15 minutes before reperfusion (n = 12). Evans blue dye was injected into half of the rats in all groups. We assessed the degree of pulmonary tissue injury by measuring activities of oxidative and antioxidative enzymes, as well as nitrate (NO(3)(-))/nitrite (NO(2)(-)) levels, biochemically. We evaluated acute lung injury (ALI) by establishing pulmonary neutrophil sequestration and ALI scoring histopathologically. Pulmonary edema was estimated by using Evans blue dye extravasation and wet/dry ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. RESULTS: APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the lung tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes (P < .05). Pulmonary neutrophil sequestration and ALI scores were decreased significantly with APC administration (P < .05). In addition, APC treatment significantly alleviated pulmonary edema (P < .05). CONCLUSIONS: This study clearly showed that APC treatment significantly attenuated the lung reperfusion injury. Further clinical studies are required to clarify whether APC has a useful role in the reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

The use of the retinal nerve fiber layer thickness measurement in determining the effects of cardiopulmonary bypass procedures on the optic nerve.

BACKGROUND: Our aim was to determine the effects of cardiopulmonary bypass procedures on the optic nerve by retinal nerve fiber layer thickness measurements. METHODS: Retinal nerve fiber layer thickness was measured using the GDx Nerve Fiber Analyser, 1 day before the surgery and on postoperative days 1, 5 and 30 in 20 patients undergoing coronary artery bypass grafting surgery. RESULTS: Postoperative mean values for retinal nerve fiber layer thickness, except symmetry on the first day and except symmetry and superior nasal ratio on the fifth day, were statsitically decreased. Only the value for the inferior ratio was significantly lower at the end of the first month. CONCLUSIONS: Cardiopulmonary bypass procedures cause a temporary decrease in retinal nerve fiber layer thickness.

Bilateral drop-foot after orthotopic liver transplant.

Patients may demonstrate various neuromuscular abnormalities after liver transplantation. We report a patient who developed bilateral drop foot after orthotopic liver transplantation. He was diagnosed with critical illness polyneuropathy. During follow-up, his complaints gradually recovered and his electrodiagnostic findings improved.

Lumbar disc herniation and tight hamstrings syndrome in adolescence.

BACKGROUND: Lumbar intervertebral disc herniation is infrequently encountered in children and adolescents. Additional signs and symptoms such as postural deformities and abnormal gait accompany the classical findings of lumbar root irritation. These unusual signs have been described in the literature as "tight hamstrings syndrome". Waddling gait with flexed knees is considered as pathognomonic for this condition and may be masked by the signs of root irritation due to prolapsed intervertebral disc material. CASE REPORT AND DISCUSSION: We report an adolescent patient with lumbar disc herniation in whom gait abnormality and limitation of lumbar movements persisted after surgical intervention. A review of the literature on tight hamstrings is presented.

Phychiatric problems of the blind: Anxiety; Somatoform; and Depressive Disorders. Menelik II Hospital; Addis Ababa; Ethiopia

Objective: To determine the magnitude of anxiety; somatoform and depressive disorders among blind people. Methods: All blind patients (according to WHO definition) who attended the Out Patient Clinics; Ophthalmology Department; Menelik II Hospital; Addis Ababa; Ethiopia; from October 2000-February 2001; were interviewed using a fully structured instrument (Composite International Diagnostic Interview (CIDI) core version 2.1). Results: 107 patients with visual loss were included in the study. Six (5.6) had acute onset versus 101 (94.4) with gradual onset. 48 (44.9) had been blind for more than one year. The most common cause of blindness was cataract (n=59; 55.1); followed by glaucoma (n=20; 18.7) and retinal detachment (n=12; 11.2). Only 5 (4.7) patients had psychiatric morbidity. Generalized anxiety disorder; depressive disorder and somatoform disorder each constituted one case. Two patients had dysthymia and one patient had social phobia. Conclusion: The reported prevalence of psychiatric problems among the blind in this study is way below those of other studies conducted in medical settings as well as in the general population. Further studies to determine the magnitude of psychiatric problems among blind people by using instruments with Amharic version of known validity are recommended; and the need to establish validity of the Amharic version of CIDI is stressed

Possible role of K-ras oncogene in mutagenic activity of ethylnitrosourea on lymphocyte hyperproliferation in rat colon.

N-ethyl-N-nitrosourea (ENU) is a potential carcinogenic agent that is commonly used in industry. Therefore the present study aimed to find out the possible effects of this agent on the rat digestive tract especially on the colon. We have studied the complementary mutation activity of the exon 2 of K-ras oncogene by ENU treatment in rat colonal tissue. While the two experimental group rats were injected once a week with 20 mg/kg and 300 mg/kg body weight-body weight with ENU (i.p.), the last experimental group was administered only with PEG and the control group animals received no treatment. Following 45 weeks, all animals were sacrificed and colonal tissues were obtained. Tissues were processed for light and electron microscopy and also for molecular biological analyses. While no colonal tumour development was observed in the control and in the PEG treated group, an extensive tumour development was seen in a wide range of tissues in the high dose ENU treated group. The light and electron microscopical examination of the rat colonal tissue revealed a lymphocyte hyperproliferation in the submucosal region, an increased number of polymorphonuclear leukocytes (PMLs) and occasional epithelial lesions. The mutation analyses of exon 2 of K-ras by HpaII demonstrated more than one recognition sites in the ENU treated group whereas there was only one enzyme cognate site in the control group.

Psychosocial function, clinical status, and radiographic findings in a group of chronic low back pain patients.

Low back pain is considered a problem with multiple facets for which the underlying causative factors should be determined. The aim of this study was to evaluate the relationships between depression, clinical status, and radiographic findings in a group of fifty patients with low back pain for more than 6 months. The patients underwent clinical examination and they completed Beck depression inventory (BDI), Aberdeen back pain scale (ABPS) and research questionnaire. Radiographic evaluations were performed. Clinical score and duration of symptoms were found to be positively correlated. The BDI scores were not found to be correlated with the existing variables. The ABPS scores were positively correlated with clinical scores and number of medications used.

Effects of a DNA demethylating agent--5-azacytidine--on testicular morphology during mouse embryo development.

DNA methylation is an epigenetical mechanism that plays crucial roles in cellular differentiation and tissue development in embryogenesis. The aim of the present study was to determine the effects of a demethylating agent, 5-azacytidine, on testicular development during embryonal life in mouse. Ten pregnant mice were administered 5-azacytidine (5-azaC) (i.p. 2 mg/kg of agent dissolved in 0.1 mg/ml PBS) during 8th (Group 1), 11th (Group 2), 14th (Group 3) and 18th (Group 4) days of pregnancy periods and male siblings of these animals were obtained (experimental groups) whereas the control group animals received no treatment and siblings of this group were also obtained. Testicular tissues from all groups were taken 20 days after birth and examined at the light and electron microscopical levels. All pregnancies were terminated in Group 1 animals, therefore no observations could be done in this group. While Group 2 and 3 siblings showed distinctive kongenital abnormalities such as; anancephaly, growth failure, cleft palate, extremity abnormalities, supernumerary ribs and whirled shaped-tails, no such abnormalities were observed in Group 4 when compared to the control group. Microscopical examination of testicular tissues in groups 2 and 3 demonstrated cellular disintegration of spermatocytes in seminiferous tubules. In addition, cytoplasmic vacuoles and thickening of the basement membrane were also evident in both groups 2 and 3. Apoptotic-like cells were seen especially in group 2 and rarely in group 3. There were no structural alterations in group 4 animals, except a decreased number of spermatocytes in seminiferous tubules when compared to the control group, possibly indicating the completion of embryogenesis in this group. In conclusion, it could be suggested that the demethylating agent 5-azacytidine may trigger an unknown gene reactivation during early embryogenesis possibly affecting the cell and tissue differentiation in developing mammalian embryos.

Double G0/G1 peak in the DNA histogram of aberrant marker positive acute leukemia patients is associated with a poor clinical outcome.

In order to investigate the relationship between aberrant marker expression and DNA ploidy, 61 adult patients with acute leukemia (39 AML and 22 ALL) were studied. Aberrant marker expression was observed in 20 patients (16/39 of AML and 4/22 of ALL patients). In flow cytometric DNA analysis aneuploidy was observed in 18 patients (9/39 of AML and 9/22 of ALL patients). The incidence of aneuploidy in patients with aberrant marker expression was 35% whereas this was 26.8% in patients without aberrant marker expression. Furthermore, 7 patients with aberrant marker expression showed an aneuploid, double G0/G1 peaks appearance whereas the remaining 11 patients with aberrant marker expression had euploid DNA content. Double G0/G1 appearance was not observed in patients without aberrant marker expression. Further analyses revealed that this did not correlate with apoptosis. All 7 patients, who had both aberrant marker expression and double G0/G1 peak had a poor clinical outcome with a short survival and all died within three months whereas three-months survival was 67% for AML, 69% for ALL patients and 81% for patients with aberrant marker expression respectively (p<0.01). Our data indicate that the evaluation of the DNA ploidy in patients with aberrant marker expression may be of prognostic importance.

Carnitine deficiency in diabetes mellitus complications.

In this study, the serum total, free and ester carnitine levels in 24 type II diabetes mellitus (DM) patients with complications and 15 type II DM patients with no complications were investigated. The patients were investigated in four groups; the control group included the patients with no complications (group 1), the groups including the patients with retinopathy (group 2), hyperlipidemia (group 3), and neuropathy (group 4). In addition, patients were grouped into two. The first group included 10 patients who took insulin by injection (group 5), and the second group included 29 patients using antidiabetic drugs orally (OAD) (group 6). Free and ester carnitine levels were determined by using Boehringer Manheim UV-enzymatic L-carnitine kit. Statistical analysis results showed that both the plasma total and free carnitine levels of groups 2, 3, and 4 were found to be low when compared to the levels of group 1 (p < 0.05). It was observed that the plasma total and free carnitine levels of group 5 were lower when compared to group 6. No significant difference was observed between the plasma ester carnitine levels of all the groups investigated. As a result of this study, it has been thought that carnitine plays an important role in diabetes mellitus complications.

Vitamin C induced oxidation of eye lens gamma crystallins.

Crystallins are long-lived proteins of the eye lens that have specific structures that maintain lens transparency. Lens crystallins are known to undergo changes with age that include oxidation. Oxidation may contribute to cataract development. In this study the effect of metal-catalysed oxidation of vitamin C (ascorbate) on gamma-crystallins was investigated based on polyacrylamide gel electrophoresis and electrospray mass spectrometry. Cross-linking, aggregation and denaturation occurred when two members of the gamma-crystalline family, gamma B and gamma S, were challenged with copper (II) and ascorbate. These proteins form a dimer, with copper alone or with the addition of ascorbate, which may be an early marker of oxidation. It was found that alpha-ketoglutarate and pyruvate were very effective in the inhibition of oxidation.

Age-specific PSA reference ranges in a group of non-urologic patients.

Age-specific serum PSA reference ranges have recently been proposed to be more sensitive in young and more specific in elder patients. However, some conflicting results have been reported from different centers. In order to establish age-specific PSA reference ranges for our country, we measured the serum PSA levels of 400 healthy men over 40, between February 1995 and June 1996. Our study population consisted of men who had either PSA values lower than 4.0 ng/ml and normal digital rectal examination or negative prostatic biopsies taken for any reason. IMX assay was used for PSA determination in all patients. Mean PSA values and standard deviations for each age group were: 1.7+/-1.1 ng/ml for 40-49 years (n = 28), 2.0+/-1.2 ng/ml for 50-59 years (n = 110), 2.9+/-1.7 ng/ml for 60-69 years (n = 158) and 3.5+/-2.0 ng/ml for 70-79 years (n = 104). We conclude that further studies of larger series will lead us to standardize age-specific reference ranges in our country and, accordingly, we will be able to select the candidates for prostate biopsy more adequately.