It is known that in animals with increased intracranial pressure the cerebral perfusion is curtailed, but whether it is caused by deranged responsiveness of the cerebral vessel is not known. Thus, it was attempted in this study to find out the changes of cerebrovascular response to Kallikrein in the rabbits with increased ICP(20mmHg) under urethane-anesthesia. 1) intracarotid arterial kallikrein elicited increases in cerebral blood flow and decreases in blood pressure and arterial resistance. 2) Cerebral blood flow was significantly decreased in rabbits with increased ICP in comparison with the control rabbits. 3) Intraarterial kallikrein caused dose-depent increases of cerebral blood flow in both groups, but responses were significantly reduced in ICP-elevated group. 4) Kallikrein produced dose-dependent hypotensive effect in both groups with no significant difference between both groups. 5) Cerebrovascular resistance was greater in rabbits with elevated ICP(20 mmHg), but kallikrein induced decreases of cerebrovascular resistance in both groups to the same degree, 6) Above results suggested that increased ICP reduces the cerebral blood flow by increasing cerebrovascular resistance, but it does not modify the reponsiveness of cerebral vessel to kallikrein.
Animals ; Blood Pressure ; Intracranial Pressure ; Kallikreins* ; Perfusion ; Rabbits*

PURPOSE: To evaluate the relationship between levels of total testosterone and total prostate-specific antigen (PSA) in healthy men with PSA<4 ng/mL. MATERIALS AND METHODS: The study comprised 179 men with a mean age of 59.19+/-12 years who visited Osmaniye State Hospital, Osmaniye, Turkey, between January 2006 and January 2007 for a routine checkup. The patients were divided into two subgroups: patients with PSA<2.5 mg/ml (group I, n=160 patients) and patients with PSA of 2.5 to 4 ng/mL (group II, n=19 patients). The relationship between PSA and testosterone levels was investigated in both groups and in patients aged <60 years. The mean testosterone level was calculated for patients aged <50 years and was compared with the mean value of patients aged > or =50 years. RESULTS: In all patients, the mean values for serum PSA and total testosterone were 1.27+/-0.88 ng/mL and 404.04+/-158.86 ng/mL, respectively. No correlation was detected between serum PSA and testosterone levels in either subgroup (group I, r=0.072, p=0.363; group II, r=0.031, p=0.900) or in patients aged <60 years (r=0.032, p=0.72). The mean values of testosterone in patients aged > or =50 years and in patients aged <50 years were 417.01+/-163.35 and 344.16+/-120.21 ng/dL, respectively (p=0.02). CONCLUSIONS: No impact of testosterone was found on the PSA level in healthy men with PSA <4 ng/mL. Therefore, a high serum testosterone level may not mandate adjustment of PSA values. This serum sex hormone showed a significant increment after the age of 50 years. Further studies including a larger number of patients should be carried out to confirm these findings.
Aged ; Aging/blood ; Humans ; Kallikreins/*blood ; Male ; Middle Aged ; Prostate-Specific Antigen/*blood ; Reference Values ; Testosterone/*blood ; Tumor Markers, Biological/blood

Thromboelastography(TEG) is the unique measure that gives rapid information about the whole clotting process. Simplifying the diagnosis of coagulopathy during operations, TEG can provide an adequate therapy for postoperative bleeding. Remarkable improvement in hemostasis after cardiopulmonary bypass(CPB) has been achieved by the treatment with proteinase inhibitor aprotinin, but the hemostatic mechanism of aprotinin during CPB is still unclear. This study was designed to evaluate the effects of aprotinin on coagulation system during CPB by using TEG. Forty patients who underwent CPB were divided into two groups: aprotinin(2 X 10(6) kallikrein inhibition units, as a single dose into the cardiopulmonary bypass priming solution) treatment group(male 14, female 8, mean age=50.8years) and no aprotinin treatment(control) group(male 10, female 8, mean age=53.4 years). TEG, activated clotting time, prothrombin time, activated partial thromboplastin time, platelet counts, fibrinogen and fibrinogen degradation product(FDP) concentrations were checked before and after CPB(30 minutes after neutralization of heparin effect by protamine sulfate). There was no significant difference in other conventional coagulation tests of two groups except postcardiopulmonary bypass FDP concentration in control group, which was significantly increased compared to that in aprotinin group(p<0.05). In TEG variables of both groups, clot formation time(K) and alpha angle(alpha degree) were significantly increased and decreased, respectively, after CPB(p<0.05), but fibrinolytic index(LYS60) was not changed during CPB. In aprotinin group, reaction time(R) was decreased significantly after CPB(p<0.05) but maximum amplitude(MA) was not changed(p>0.05). On the contrary, R was not changed markedly but MA was decreased significantly in control group after CPB(p<0.05). This result shows that the main change in coagulation system during CPB is not hyperfibrinolysis but decrease in clot strength by platelet dysfunction, and the main effect of aprotinin during cardiopulmonary bypass is the maintenance of clot strength to the pre-CPB level by the preservation of platelet function.
Aprotinin* ; Blood Platelets ; Cardiopulmonary Bypass* ; Diagnosis ; Female ; Fibrinogen ; Hemorrhage ; Hemostasis ; Heparin ; Humans ; Kallikreins ; Partial Thromboplastin Time ; Platelet Count ; Prothrombin Time

PURPOSE: The purpose of this study was to evaluate whether neo-adjuvant hormonal therapy (NHT) prior to radical retropubic prostatectomy (RRP) for prostate cancer (PCa) is beneficial in terms of surgical outcomes and for preventing or delaying biochemical recurrence via single-surgeon case series study. MATERIALS AND METHODS: Fifty-three men underwent RRP by a single surgeon. The patients were divided into two groups according to whether or not NHT was performed prior to RRP. The study was analyzed retrospectively. We evaluated clinical parameters, surgical parameters, and biochemical recurrence rate. Group 1 (n=34) was treated with RRP only, while Group 2 (n=19) underwent RRP along with NHT. RESULTS: There were no significant differences in clinical, operation-related and pathological factors between the two groups (p>0.05). There was also no significant difference in biochemical recurrence rate between the two groups at the last follow-up, although Group 2 tended to have a lower PCa recurrence rate than Group 1 and the initial prostate-specific antigen (PSA) level was significantly higher in Group 2 than Group 1 (p=0.0496). CONCLUSION: The present single-surgeon case series study revealed a trend toward a lower rate of PCa recurrence in NHT+RRP treated patients compared to those treated with RRP alone, but this did not reach statistical significance, despite the fact that NHT+RRP patients exhibited higher serum PSA levels preoperatively. Prospective studies with a longer duration of observation and a greater number of patients would be helpful in evaluating NHT more definitively.
Humans ; Kallikreins/blood ; Male ; *Neoadjuvant Therapy ; Preoperative Period ; Prostate-Specific Antigen/blood ; *Prostatectomy ; Prostatic Neoplasms/*drug therapy/surgery ; Recurrence ; Retrospective Studies

The purpose of this study was to determine whether contemporary active surveillance (AS) protocols could sufficiently discriminate significant from indolent tumors in men with low-risk prostate cancer. We retrospectively analyzed 312 patients with low-risk prostate cancer treated with radical prostatectomy. After exclusion of patients with fewer than 10 cores taken at biopsy and those who received neo-adjuvant treatment, 205 subjects satisfied the final inclusion criteria. Five widely accepted AS protocols were employed in this study. A total of 82.0% of the patients met the inclusion criteria of at least one protocol, and 18% did not meet any criteria of published AS protocols. A significant proportion of patients had non-organ-confined disease (8.6% to 10.6%) or a Gleason score of 7 or greater (18.6% to 23.9%) between the different AS criteria. Among patients who did not meet any AS criteria, 32.4% of patients had a pathologically insignificant cancer. Our results indicated a significant adverse pathology in patients who met the contemporary AS protocols. On the other hand, some patients in whom expectant management would be appropriate did not meet any criteria of published AS protocols. None of the clinical or histological criteria reported to date is able to sufficiently discriminate aggressive tumors from indolent ones.
Aged ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prostate/*pathology ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; Risk Assessment ; Treatment Outcome ; *Watchful Waiting

OBJECTIVETo find sensitive and specific micro-metastic markers for prostate cancer.

METHODSUsing nested reverse transcription-PCR, we examined the expression of PSA, hK2 and PSMA mRNA in peripheral blood mononuclear cells of 51 patients with prostate cancer, 33 patients with benign prostate hyperplasia (BPH) and 32 normal young people.

RESULTSThe expression rates of PSA, hK2 and PSMA mRNA were 52.9%, 43.1% and 64.7%, respectively in prostate cancer group, and 6.2%, 7.7% and 4.6%, respectively in control group (BPH patients and normal young people) with statistical significance (P < 0.01). Although the expression rate of PSA and hK2 mRNA increased with cancer progression, there was no statistical significance among patients in different stages. The expression rate of PSMA mRNA was higher than that of PSA and hK2 mRNA in each clinical stage.

CONCLUSIONPSMA mRNA expression detected by nested RT-PCR is of greater value for the diagnosis, therapy choice and prognostic evaluation of prostate cancer patients.

Aged ; Antigens, Surface ; blood ; Biomarkers, Tumor ; blood ; Glutamate Carboxypeptidase II ; blood ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; blood ; pathology ; Prostatic Neoplasms ; blood ; pathology ; Tissue Kallikreins ; blood

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.
Atrial Natriuretic Factor ; Blood Pressure ; Brain ; Central Nervous System ; Diuresis ; Filtration ; Hemodynamics ; Hypotension ; Kallidin* ; Kallikreins* ; Natriuresis ; Natriuretic Agents ; Neurotransmitter Agents ; Plasma ; Renal Circulation ; Sodium ; Water

Aprotinin is a serine protease inhibitor and a powerful antifibrinolytic agent, derived from the inhibition of plasmin and kallikrein. Therefore, it is widely used in cardiopulmonary bypass surgery or major surgery for reducing bleeding and blood transfusion requirements. Aprotinin is rapidly eliminated from the circulation by glomerular filtration and is actively reabsorbed in the renal tubular system, where it is stored, metabolized, and eliminated over the following 5-6 days. Because of this metabolism, concerns have been raised regarding the possibility that aprotinin may impair renal function due to a toxic effects on proximal tubular cells. We report three cases of postoperative renal failure after aprotinin had been used during surgery. Two patients, Jehovah's Witnesses who refused blood transfusion, required hemodialysis. One patient, who underwent spinal orthopedic surgery, was administered aprotinin to reduce intraoperative blood loss, and developed acute renal dysfunction. The patient recovered after supportive therapy.
Acute Kidney Injury* ; Aprotinin* ; Blood Transfusion ; Cardiopulmonary Bypass ; Fibrinolysin ; Filtration ; Hemorrhage ; Humans ; Jehovah's Witnesses ; Kallikreins ; Metabolism ; Orthopedics ; Renal Dialysis ; Renal Insufficiency ; Serine Proteases

PURPOSE: Prostate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma. MATERIALS AND METHODS: A total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-microm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension. RESULTS: Our results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence. CONCLUSIONS: The value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.
Adult ; Aged ; Biopsy, Needle ; Fractals ; Humans ; Image Processing, Computer-Assisted/methods ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/*pathology ; Prostate/*blood supply ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*blood supply/pathology/surgery ; Retrospective Studies

PURPOSE: We are often confronted with patients in the "gray zone" (prostate-specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients without prostate cancer (PC). MATERIALS AND METHODS: We studied 106 men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who had no clinical prostatitis. Inflammation observed at biopsies was scored for inflammation type in each biopsy core by use of a four-point scale and was then correlated with tPSA, fPSA, and f/tPSA. RESULTS: Different patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type: more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA (p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammation type (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in that the fPSA and f/tPSA were lower in the group with more acute inflammation. CONCLUSIONS: Subclinical inflammation has a significant influence on fPSA in patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammation is not characterized by elevated tPSA alone but also by a decreased fPSA, a tendency similar to that in PC.
Acute Disease ; Aged ; Aged, 80 and over ; Asymptomatic Diseases ; Biopsy, Large-Core Needle ; Chronic Disease ; Diagnosis, Differential ; Humans ; Kallikreins/*blood ; Male ; Middle Aged ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/blood/diagnosis ; Prostatitis/*blood/diagnosis/pathology