PubMed Health⌕ Search

Biomedical subjects

M Ates

Publications and source records attributed to M Ates.

16 recordsLinked to original sources
PubMed2002

A novel method to quantify mechanical tension in cell monolayers.

A new technology to analyze mechanical properties of adherent cell monolayers grown on elastic silicon membranes is introduced. Measurements were performed using 3T3 (NIH) fibroblasts under the influence of Cytochalasin D and Thrombin. The stress-strain relation of the cell monolayer-silicon-composite was monitored. The drum-like construct of the culture chamber opens new roads for studying the mechanics of cell monolayers and of ultra flat tissue constructs. Steady state as well dynamic mechanical studies can be performed. Defined mechanical boundary conditions together with the known number and orientation of the cells allow precise information on the average tension exerted by a single cell within the monolayer.

3T3 Cells↗
PubMed2001

HU-210 shows higher efficacy and potency than morphine after intrathecal administration in the mouse formalin test.

The discovery of endocannabinoids opens up new perspectives in experimental pain research. Here we present data for the excellent antinociceptive properties of the synthetic cannabinoid, R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), after intrathecal and oral administration in mice. It is known that cannabinoids depress motor activity. Therefore, these compounds are suspected of influencing antinociceptive tests. Our behavioural tests (RotaRod, tail flick) clearly show that HU-210 affects nociceptive behaviour even at dosages which do not yet influence motor activity. Moreover, spinal microdialysis (5 microl/min) in the dorsal horn of freely moving mice showed an enhancement of prostaglandin production during the formalin test. HU-210 applied via artificial cerebral spinal fluid during microdialysis perfusion increases prostaglandin concentrations under both baseline and formalin test conditions. Indomethacin reduces the HU-210 effect on pronociceptive prostaglandin production but does not reinforce the antinociceptive properties of HU-210. Thus, HU-210 shows antinociceptive properties that are independent of its influence on the prostaglandin pathway.

Analgesics, Opioid↗
PubMed2001

Ketoprofen-induced cyclooxygenase inhibition in renal medulla and platelets of rats treated with caffeine.

It has been suggested that caffeine can augment analgesic activity and aggravate side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of the present study was to investigate a possible interaction between ketoprofen and caffeine on prostaglandin (PG) biosynthesis and cyclooxygenase (COX) mRNA expression in the rat renal medulla ex vivo. Treatment of rats with ketoprofen (60 min before) resulted in a dose-dependent (estimated ID(50) 0.3 mg/kg p.o.) reduction of PGE(2) biosynthesis in renal medulla ex vivo. Ketoprofen (0.3 mg/kg)-induced inhibition of PGE(2) biosynthesis was stable between 30 and 180 min and still detectable 300 min after drug administration. Caffeine (10 mg/kg) did not cause a detectable effect on its own, nor did it significantly affect ketoprofen-induced inhibition of renal medullary PGE(2) biosynthesis. Similar results were obtained with repeated daily drug administration for 1 week: there was no significant effect of caffeine on ketoprofen-induced inhibition of renal medullary PGE(2) biosynthesis. The absence of significant caffeine effects on ketoprofen-induced inhibition of renal medullary PGE(2) biosynthesis was paralleled by experiments showing no significant effect of caffeine on ketoprofen-induced inhibition of platelet thromboxane (TX)B(2) biosynthesis. Additional experiments showed increased COX-2 mRNA expression in the renal medulla 60 min after ketoprofen administration, that was not significantly influenced by concomitant caffeine treatment. Treatment of rats with ketoprofen for 1 week had no significant effects on COX-2 mRNA expression. The present results show that ketoprofen caused inhibition of PGE(2) biosynthesis in the rat renal medulla ex vivo with a potency similar to that reported for in vivo models suggesting that the ex vivo approach is a valid model to test a possible interference of caffeine with ketoprofen-induced COX inhibition. The absence of detectable effects of caffeine on time course or magnitude of ketoprofen-induced suppression of PGE(2) biosynthesis in this model indicates, therefore, that possible adverse actions of co-administered caffeine on renal function are not related to interference with renal COX inhibition.

Animals↗
PubMed2000

Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced early thermal hyperalgesia in iNOS-deficient mice.

It is widely accepted that peripheral injury increases spinal inducible cyclooxygenase (COX-2) expression and prostaglandin E(2) (PGE(2)) formation as key mediators of nociceptive sensitization. Here, we used inducible nitric oxide synthase (iNOS) gene-deficient (iNOS-/-) mice to determine the contribution of iNOS-derived nitric oxide (NO) to this process. iNOS-/- mice exhibited reduced thermal hyperalgesia after zymosan injection. Spinal NO and PGE(2) formation both remained at baseline levels, in contrast to wild-type (wt) mice. In wt mice reduced hyperalgesia similar to that seen in iNOS-/- mice was induced by local spinal, but not by systemic treatment with the iNOS inhibitor l-NIL, suggesting that the reduced heat sensitization in iNOS-/- mice was attributable to the lack of spinal rather than peripheral iNOS. Two additional observations indicate that the antinociceptive effects of iNOS inhibition are dependent on a loss of stimulation of PG synthesis. First, intrathecal injection of the COX inhibitor indomethacin, which exerted pronounced antinociceptive effects in wt mice, was completely ineffective in iNOS-/- mice. Second, treatment with the NO donor RE-2047 not only completely restored spinal PG production and thermal sensitization in iNOS-/- mice but also its sensitivity to indomethacin. In both types of mice induction of thermal hyperalgesia was accompanied by similar increases in COX-1 and COX-2 mRNA expression. The stimulation of PG production by NO therefore involves an increase in enzymatic activity, rather than an alteration of COX gene expression. These results indicate that NO derived from spinal iNOS acts as a fast inductor of spinal thermal hyperalgesia.

Animals↗
PubMed2000

Elevated serum CA-125 levels in hemodialysis patients with peritoneal, pleural, or pericardial fluids.

OBJECTIVE: Serum CA-125, an ovarian tumor marker, is used especially in the follow-up of ovarian cancer for monitoring the efficacy of therapy and for early detection of recurrence. A number of benign gynecologic as well as benign and malignant nongynecologic conditions are associated with elevated serum CA-125 levels. Malignant and nonmalignant serosal fluids were also found to be associated with high serum levels of CA-125, suggesting that the presence of fluid in the serosal cavities may stimulate its release. METHODS: We performed a clinical study in 39 patients (21 females, 18 males) on chronic hemodialysis who were divided into two groups based on the presence of fluid in the serosal cavities (peritoneum, pleura, or pericardium) without clinical and radiologic evidence of neoplasia. There were 26 patients (16 females, 10 males) aged 50.11 +/- 13.86 years (range, 20-76 years) in the serosal fluid-negative group (group 1) and 13 patients (8 females, 5 males) aged 45.30 +/- 18.84 years (range, 17-73 years) in the serosal fluid-positive group (group 2). The control group consisted of 52 healthy volunteers (30 females, 22 males) aged 44.19 +/- 12.59 years (range, 19-68 years). RESULTS: Significantly elevated serum CA-125 levels were found in hemodialysis patients with serosal fluid (P < 0.05) when compared with both the hemodialysis patients without serosal fluid and the control group. There was no statistically significant difference between the control group and the patients without serosal fluids (P > 0.05). CONCLUSION: Although CA-125 can be considered a reliable tumor marker in patients undergoing hemodialysis, it should be interpreted with caution in patients with serosal fluids.

Adult↗
PubMed2000

The effects of abdominal and bimanual pelvic examination and transvaginal ultrasonography on serum CA-125 levels.

The need for the early detection of ovarian cancer continues to be one of the most important issues in women's health care. The three most extensively evaluated screening methods for ovarian cancer are pelvic examination, transvaginal ultrasonography, and serum CA-125 levels. The answers to questions such as should the levels of CA-125 be measured before bimanual pelvic examination or transvaginal ultrasonography or do abdominal examinations effect the levels of CA-125 are obscure. Fifty-four otherwise healthy female volunteers at the preovulatory phase of the menstrual cycle complaining of vaginal candidiasis were divided into 3 groups. Abdominal (group 1), bimanual pelvic (group 2), and transvaginal ultrasonography (group 3) examination was performed and serum CA-125 levels were evaluated prior to examination and 10 minutes, 6 hours, and 24 hours after the examination. As a result, serum CA-125 levels (U/ml) were found to be 8.13 +/- 4.76, 8.23 +/- 5.05, 8.32 +/- 4.88, and 8.33 +/- 4.94 in the group of abdominal examination, respectively, 8.23 +/- 4.89, 8.45 +/- 5.15, 8.77 +/- 4.96, and 8.79 +/- 5.50 in the group of bimanual pelvic examination, respectively, and 8.19 +/- 4.56, 8.30 +/- 5.10, 8.81 +/- 5.56, and 8.88 +/- 5.71 in the group of transvaginal ultrasonography, respectively. The serum CA-125 levels detected prior to examinations were statistically insignificant when compared with the results obtained at 10 minutes, 6 hours, and 24 hours later in all three groups. We concluded that physical examination, either abdominal or pelvic, and transvaginal ultrasonography do not change the serum levels of CA-125.

Adult↗
PubMed1998

The effects of 4-aminopyridine and Bay K 8644 on verapamil-induced cardiovascular toxicity in anesthetized rats.

OBJECTIVE: To determine the effects of 4-aminopyridine and Bay K 8644 on mean arterial pressure and heart rate in an anesthetized rat model of verapamil toxicity. METHODS: The study was a randomized, controlled animal study. Rats were anesthetized and the carotid artery was cannulated for mean arterial pressure and heart rate measurements while both jugular veins were cannulated for drug administration. All animals were infused with verapamil (15 mg/kg/h i.v.) until 45-60% reduction of mean arterial pressure and 30% reduction of heart rate were observed. After verapamil, control animals were given normal saline solution and the other groups received 4-aminopyridine (1 and 2 mg/kg/h) or Bay K 8644 (0.3 and 0.6 mg/kg/h) for 60 minutes. RESULTS: While 4-aminopyridine (1 mg/kg/h i.v.) did not significantly increase mean arterial pressure (75.9 +/- 5.5%) when compared with the control group (64.3 +/- 5.1%, p > 0.05), 2 mg/kg/h i.v. of 4-aminopyridine improved mean arterial pressure within 40 minutes (87.4 +/- 6.6%, p < 0.05, 95% CI 66.4-108.6%). Because the 2 mg/kg/h 4-aminopyridine produced side effects including seizures, secretions, and fasciculations at 35 +/- 5 minutes, the infusion was stopped at that time. Only the 2 mg/kg/h 4-aminopyridine infusion increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 283.2-364.4). Bay K 8644 (0.3 and 0.6 mg/kg/h i.v.) significantly enhanced mean arterial pressure within 5 minutes (68.0 +/- 4.1% and 73.0 +/- 2.9%, respectively, p < 0.05), (95% CI 56.8-78.0% and 95% CI 64.9-81.1%, respectively) but no significant changes in mean arterial pressure were observed after 5 minutes. The 4-aminopyridine (2 mg/kg/h) increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 311.3-358.7). Bay K 8644 did not produce a significant effect on heart rate (p > 0.05). CONCLUSIONS: 4-Aminopyridine improved mean arterial pressure and heart rate in a dose-dependent fashion; however, the higher infusion rate (2 mg/kg/h) necessary to improve mean arterial pressure and heart rate resulted in convulsions and excessive secretions. The reversal effects of Bay K 8644 on mean arterial pressure were transient and did not affect heart rate.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model.

1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.

Amrinone↗
PubMed1996

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats.

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/ kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP. Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.

Amrinone↗
PubMedDate not supplied

The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus.

We evaluated the possible relation between plasma endothelin-1 (ET-1) levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy, including nephropathy, neuropathy, and retinopathy in patients with Type 2 diabetes and healthy control group. Sixty-eight (39 females and 29 males) patients with Type 2 diabetes and 14 (6 females and 8 males) healthy subjects were included in the study. Plasma ET-1 levels were found to be 10.46+/-1.24 pmol/l in the diabetic group, whereas 7.97+/-0.41 pmol/l in the control group, which was statistically significant (P<.01). We also found elevated plasma ET-1 levels in patients with the least one microvascular complication when compared with the uncomplicated diabetes group (P=.02). Moreover, plasma ET-1 levels of the uncomplicated group was higher than the control group (P<.05). Plasma ET-1 levels were significantly elevated in hypertensive diabetics than normotensive diabetics (t=2.58, P=.012). It was also found to be elevated in diabetic patients with diabetes duration of more than 10 years when compared with patients less than 10 years (P=.02). These findings can be interpreted as the increased damage of microvascular complications in the disease process that may lead to elevated ET-1 levels. Mean plasma ET-1 levels in diabetic patients with a family history of diabetes was found to be higher than patients with no family history of diabetes. Genetical and environmental factors may have an effect on ET-1 level. We also studied the correlations of plasma ET-1 levels on age, sex, fasting blood glucose levels, treatment modalities HbA1c, hyperlipidemia, C-peptide, Body Mass Index, and smoking, but did not find any statistically significant difference. In conclusion, plasma ET-1 levels are well correlated with microangiopathy, hypertension, increased disease duration, and family history of diabetes, but poorly correlated with metabolic control, treatment modalities, age, sex, hyperlipidemia, obesity, and smoking.

Adult↗
PubMedDate not supplied

Elevated serum CA-125 levels in patients with nephrotic syndrome-induced ascites.

CA-125 is a sensitive, but not a specific, tumour marker especially used in the diagnosis and follow-up of ovarian cancer. Because of the elevated levels of CA-125 encountered during the etiological investigation of nephrotic syndrome (NS) a clinical study was designed to investigate the probable relationship between elevated CA-125 levels in patients with NS, with and without ascites. Twenty-four patients with NS due to non-tumoural pathologies, aged 24 to 56 (15 females and 9 males), were investigated. We detected elevated levels of serum CA-125 (275.92 +/- 154.71 U/mL) in 14 (70%) NS patients with ascites (p < 0.05). In the other 10 NS patients without ascites (Group 2) and in the control group, consisting of 52 age and sex-matched healthy volunteers, the serum CA-125 levels were found to be 13.60 +/- 5.12 U/mL and 8.50 +/- 5.02 U/mL, respectively (p > 0.05). There was no statistically significant difference between the control group and the patients without serosal fluids (p > 0.05). We concluded that serum CA-125 levels were elevated in NS patients with ultrasonographically detected ascites in the absence of an ovarian tumour or other diseases known to increase the levels of CA-125.

Adult↗