Association of male pattern baldness with angiographic coronary artery disease severity and collateral development.

OBJECTIVE: We aimed to investigate whether there is an association between male pattern baldness and angiographic coronary artery disease (CAD) severity and collateral development, which has not been reported previously. METHODS: Coronary arteriograms, CAD risk factors, lipid parameters and presence and severity of baldness in 511 male patients were prospectively evaluated. Baldness was classified into five groups. Severity of CAD was evaluated with the Gensini scoring system and collateral development with Rentrop scores. RESULTS: Although subjects with a higher Gensini score had more frequent and severe baldness, they were older than the group with lower Gensini scores. Bald patients had a higher Gensini score when compared with their non-bald counterparts. In univariate analysis, age more than 60, body mass index more than 30, smoking and baldness were predictors of high Gensini scores. In multivariate analysis, only age more than 60, body mass index more than 30 and smoking were independent predictors of a high Gensini score. There were no differences in terms of presence and severity of baldness in subjects with and without adequate collateral development. CONCLUSIONS: There was no relation between presence, severity and age of occurrence of male pattern baldness and Gensini and Rentrop scores, which are important measures of presence and severity of CAD.

Highly stable laccase from repeated-batch culture of Funalia trogii ATCC 200800.

The effect of temperature, pH, different inhibitors and additives on activity and stability of crude laccase obtained from repeated-batch culture of white rot fungus Funalia trogii ATCC 200800 was studied. The crude enzyme showed high activity at 55-90 degrees C, which was maximal at 80-95 degrees C. It was highly stable within the temperature intervals 20-50 degrees C. The half life of the enzyme was about 2 h and 5 min at 60 degrees C and 70 degrees C, respectively. pH optimum of fungal laccase activity was revealed at pH 2.5. The enzyme from F. trogii ATCC 200800 was very stable between pH values of 3.0-9.0. NaN3 and KCN were detected as the most effective potent enzyme inhibitors among different compounds tested. The fungal enzyme was highly resistant to the various metal ions, inorganic salts, and organic solvents except propanol, at least for 5 min. Because of its high stability and efficient decolorization activity, the use of the crude F. trogii ATCC 200800 laccase instead of pure enzyme form may be a considerably cheaper solution for biotechnological applications.

Perioperative airway management strategy and posttransplant successful tracheal resection and reconstruction in a heart transplant candidate with post-intubation stenosis.

Post-intubation tracheal stenosis (PTS) is an important clinical situation. It is estimated to occur in approximately 5% to 20% of intubated or tracheostomized patients. PTS most commonly occurs after prolonged intubation, and the treatment options have been well discussed in the literature. However, in solid organ transplantation, the necessity of administering high doses of corticosteroids as well as immunosuppressive therapies may compromise the healing processes following tracheal resection and reconstruction, requiring different treatment strategies for simultaneous PTS. We present a patient suffering from end-stage heart failure and post-intubation tracheal stenosis along with our treatment strategy.

Genome-wide identification of genes that play a role in boron stress response in yeast.

Boron is an essential micronutrient for plants and it is either necessary or beneficial for animals. Studies identified only few genes related to boron metabolism thus far and details of how boron is imported into cells and used in cell metabolism are largely unknown. In order to identify genes that play roles in boron metabolism, we screened the entire set of yeast haploid deletion mutants and identified 6 mutants that were resistant to toxic levels of boron, and 21 mutants that were highly sensitive to boron treatment. Furthermore, we performed a proteomic approach to identify additional proteins that are significantly up-regulated by boron treatment. Our results revealed many genes and pathways related to boron stress response and suggest a possible link between boron toxicity and translational control.

The prevalence and significance of autoantibodies in patients with non-Hodgkin's lymphoma: are they correlated with clinicopathological features?

PURPOSE: It is well known that an association exists between the pathogenesis of lymphomas and autoimmune diseases. Autoantibodies are detected at higher frequency in lymphoproliferative diseases, but neither the precise role of the immune system nor the cause of this is comprehensively understood. In this study we evaluated the presence and significance of some autoantibodies for patients with non- Hodgkin's lymphoma (NHL). METHODS: 150 patients with NHL who had either newly diagnosed disease, or active disease being under chemotherapy or were disease-free during follow-up, were analyzed. The frequency of autoantibodies and the relationship between autoantibodies and several clinicopathological factors were evaluated. RESULTS: The majority of the patients (50%) had diffuse large B-cell lymphoma (DLBCL). Thirty-two patients (21.4%) were newly diagnosed, 81 (54%) had active disease and were receiving chemotherapy and 37 (24.6%) were disease-free and followed-up. Fifty-one patients (34%) had stage IV disease. Antinuclear antibodies (ANA) were found in 7 (4.7%) patients, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in 10 (6.7%), anti dsDNA in 1 (0.7%), anti ssDNA in 16 (10.7%), anti Jo-1 in 3 (2%), anti-scleroderma antibody (anti Scl-70) in 4 (2.7%), and rheumatoid factor (RF) in 85 (56.7%) patients. No c7horbar;ANCA positivity was found. The mean levels of anti Jo-1 (p=0.028), anti ssDNA (p=0.014), c-ANCA (p=0.015), ANA (p=0.026) and RF (p=0.046) were significantly higher in cases with DLBCL compared to patients with non-DLBCL. In addition, in patients with newly diagnosed NHL the mean levels of anti Scl- 70 (p=0.023), anti Jo-1 (p7equals;0.017), and RF (p=0.046) were significantly higher than the other patient groups. No significant correlation was detected between the presence of autoantibodies and other clinicopathological factors. CONCLUSION: Our results show that the frequency of autoantibodies is high in NHL patients, especially in DLBCL and newly diagnosed cases. Autoantibodies may be helpful for the diagnosis of autoimmune diseases, but regular and long follow-up is needed in NHL patients with high levels of autoantibodies.

Pneumonia severity indices predict prognosis in coronavirus disease-2019.

BACKGROUND: Early recognition of the severe illness is critical in coronavirus disease-19 (COVID-19) to provide best care and optimize the use of limited resources. OBJECTIVES: We aimed to determine the predictive properties of common community-acquired pneumonia (CAP) severity scores and COVID-19 specific indices. METHODS: In this retrospective cohort, COVID-19 patients hospitalized in a teaching hospital between 18 March-20 May 2020 were included. Demographic, clinical, and laboratory characteristics related to severity and mortality were measured and CURB-65, PSI, A-DROP, CALL, and COVID-GRAM scores were calculated as defined previously in the literature. Progression to severe disease and in-hospital/overall mortality during the follow-up of the patients were determined from electronic records. Kaplan-Meier, log-rank test, and Cox proportional hazard regression model was used. The discrimination capability of pneumonia severity indices was evaluated by receiver-operating-characteristic (ROC) analysis. RESULTS: Two hundred ninety-eight patients were included in the study. Sixty-two patients (20.8%) presented with severe COVID-19 while thirty-one (10.4%) developed severe COVID-19 at any time from the admission. In-hospital mortality was 39 (13.1%) while the overall mortality was 44 (14.8%). The mortality in low-risk groups that were identified to manage outside the hospital was 0 in CALL Class A, 1.67% in PSI low risk, and 2.68% in CURB-65 low-risk. However, the AUCs for the mortality prediction in COVID-19 were 0.875, 0.873, 0.859, 0.855, and 0.828 for A-DROP, PSI, CURB-65, COVID-GRAM, and CALL scores respectively. The AUCs for the prediction of progression to severe disease was 0.739, 0.711, 0,697, 0.673, and 0.668 for CURB-65, CALL, PSI, COVID-GRAM, A-DROP respectively. The hazard ratios (HR) for the tested pneumonia severity indices demonstrated that A-DROP and CURB-65 scores had the strongest association with mortality, and PSI, and COVID-GRAM scores predicted mortality independent from age and comorbidity. CONCLUSION: Community-acquired pneumonia (CAP) scores can predict in COVID-19. The indices proposed specifically to COVID-19 work less than nonspecific scoring systems surprisingly. The CALL score may be used to decide outpatient management in COVID-19.

CYP2C19 polymorphisms in patients with gastric and colorectal carcinoma.

BACKGROUND: It has been reported that up to 80% of human cancers arise as a consequence of environmental exposure and host susceptibility factors. Environmental carcinogens are predominantly metabolized by the cytochrome P450 (CYP) superfamily of drug- or xenobiotic-metabolizing enzymes. Genetic variations in these enzymes affect individuals' susceptibility to carcinogens. AIM OF THE STUDY: The aim of this study was to evaluate the relationship between CYP2C19 polymorphism and susceptibility to these cancers by means of CYP2C19 genotyping among Turkish subjects. METHODS: DNAof subjects were isolated from leukocytes by high pure template preparation kit (Roche Diagnostics, GmbH, Mannheim, Germany) and genotypes were detected by LightCycler CYP2C19 Mutation Detection Kit by real-time PCR with LightCycler instrument (Roche Diagnostics, cat. no. 3113914). RESULTS: Being male was associated with a 3.5-fold (OR: 4.27, CI: 2.27-8.05) and 4.27-fold (OR: 3.50, CI: 1.948-6.301) risk for colorectal and gastric carcinoma, respectively. The CYP2C19*3 heterozygote genotype was not found in either gastric or colorectal carcinoma patients. Although the frequency of CYP2C19*2 heterozygote genotype is high in patients with gastric and colorectal carcinoma, it is not significantly associated with cancer (OR: 1.79, CI: 0.829-3.865 and OR: 1.998, CI: 0.961-4.154, respectively). CONCLUSION: Although the frequency of CYP2C19*2 heterozygote genotype is high in our patients with gastric and colorectal carcinoma, there is no the relationship between CYP2C19 polymorphism and susceptibility to these cancer.

Role of nicotinic acetylcholine receptor subtypes on nicotine's enhancing effect on electrical field stimulation elicited contractile responses in rabbit urine bladder.

OBJECTIVE: This study aims to investigate the contribution of presynaptic nicotinic acetylcholine receptors (nAChRs) sub-types to nicotine-induced enhancement in electrical field stimulation (EFS) EFS-mediated contractile responses in rabbit urine bladder smooth muscle preparations. MATERIALS AND METHODS: Rabbit urine bladder smooth muscle strips were placed in organ baths containing 20 ml of an aerated Krebs-Henseleit solution, and contractions were recorded using isometric force displacement transducers. Following the acquisition of control EFS (60 V, 8 Hz, 1 ms) responses, nicotine was added to the bath at a 3×10-5 M concentration, and EFS responses were obtained. The effect of nAChR antagonists on nicotine-induced augmentation in EFS-mediated responses was investigated in the presence of hexamethonium, dihydro-ß-erythroidine, mecamylamine, and α-bungarotoxin. RESULTS: Tetrodotoxin (TTX; 10-6 M) completely blocked EFS-induced contractile responses in smooth muscle strips. Similarly, Atropine (10-6 M), when administered with α,ß-methylene adenosine triphosphate (α,ß-methylene-ATP) (10-5 M), completely blocked EFS responses. Nicotine significantly enhanced EFS-mediated contractile responses (23.67% ± 1.75). Nicotine-induced increases in EFS responses were largely inhibited by hexamethonium, mecamylamine, and dihydro-ß-erythroidine, whereas α-bungarotoxin only partly inhibited these enhancements. CONCLUSIONS: These findings demonstrate that EFS-induced neurogenic contractions in rabbit urine bladder smooth muscle strips are mediated by purinergic and cholinergic transmissions, and the α4ß2, α3ß4, and α7 sub-types of nAChRs contribute to the enhancement effect of nicotine on EFS-induced contractile responses.

Leukotriene C4 and prostaglandin E2 activities in the serum and cerebrospinal fluid during acute cerebral ischemia.

Lipoxygenase pathway products of arachidonic acid (AA) metabolism (known as leukotrienes, LTs) are produced in the brain during pathologic conditions such as ischemia, hemorrhage, trauma, and seizure in which the release of AA is sustained by the activation of local phospholipases. The most common type of LT in the central nervous system is an LTC4 which is a highly potent vasoconstrictor leading to increase in vascular permeability. In this study, we compared the serum (S) and cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) and LTC4 levels in 13 consecutively admitted patients with acute cerebral ischemia aged 55-80 years with 10 age-matched controls. Patients with previous glucocorticosteroid and antiinflammatory drug usage were not included in the study. S and CSF samples were drawn during the first 72 h of the attack, and samples were evaluated by bioassay. There was no significant difference in S PGE2 and LTC4 values, whereas a significant difference was observed between CSF PGE2 and LTC4 values as compared with the control group. The high levels of CSF PGE2 and LTC4-like activity in acute cerebral ischemia may indicate that these mediators have a role to play in cerebral edema. The CSF PGE2/LTC4 ratio was also found to be reduced in the ischemic group implying higher LTC4 synthesis than PGE2 synthesis. In the light of these findings, we suggest that use of a selective antagonist of LTs may be helpful in reducing the ischemic penumbra during acute cerebral ischemia by controlling the vasogenic edema.

The role of prostanoids in the complications of extracorporeal shock wave lithotripsy (ESWL) in children.

ESWL is a safe and effective first-line treatment for urinary tract stone disease (UTSD) in children. The major complications arising from this procedure were upper urinary tract obstruction and ureteral colic. It was shown that prostaglandin synthetase inhibitors were effective in the treatment of urethral colic. The aim of this study was to measure urinary and plasma prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activity in the patients who underwent ESWL before and after the treatment and investigate the role of cyclooxygenase (CO) and lipoxygenase (LO) products in early and late complications of ESWL. Urinary PGE2-like activity were increased 1 h after ESWL. (1.19 +/- 0.12 vs 1.59 +/- 0.15 g/ml, p < 0.02). The plasma values were decreased significantly after the treatment (16.7 +/- 1.7 vs 11.6 +/- 1.2 g/ml, p < 0.005). Urinary and plasma LTC4-like activities were found to be significantly decreased in the post-ESWL samples (0.58 +/- 0.006 vs 0.39 +/- 0.04, p < 0.002; 8.6 +/- 0.9 vs 4.2 +/- 0.6, p < 0.001, respectively). In conclusion, ESWL may stimulate the release of PG from the urinary tract resulting in increased peristaltism and the passage of stone fragments into the bladder. As this group of drugs has also nephrotoxic effects, they can be given prophylactically only to selected patients.

The role of plasma arachidonic acid metabolites in the pathogenesis and the prognosis of Henoch-Schönlein purpura.

Henoch-Schönlein Purpura (HSP) involve small vessel inflammation. Arachidonate biochemical pathways play an important role in the pathogenesis of vascular inflammation. The aim of this study was to investigate the change in the ratio of plasma arachidonic acid metabolites in the patients with HSP and evaluate the association between clinical activity and prostanoid activity in the acute phase of HSP. Plasma prostaglandin E2 (PGE2)-like activities were found to be 7.2 +/- 0.8 ng/ml in control group (n = 12) while it was 5.3 +/- 0.6 ng/ml in the patients with HSP (n = 12). Plasma leukotriene C4 (LTC4)-like activities were found to be 16.0 +/- 1.1 ng/ml in control while it was 30.9 +/- 4.3 ng/ml in the patients. The differences of LTC4-like activities and the LTC4/PGE2 ratios between the HSP patients and the controls were significant (p < 0.01, p < 0.001 respectively), but no significant difference was found in PGE2-like activities. Plasma LTC4-like activity and LTC4/PGE2 ratio were also significantly increased in the patients with high clinical score (p < 0.05, p < 0.02 respectively). These results suggested that not only cyclooxygenase products but also LTs may play an important role in vascular inflammation. Therefore LTC4/PGE2 ratio must be taken into consideration in the pathogenesis and the prognosis of HSP.

The effects of prostacyclin analogue ZK 36374 and thromboxane synthetase inhibitor UK 38485 on mesenteric ischemia in guinea pigs.

The effects of ZK 36374, a prostacyclin analogue and UK 38485, a thromboxane synthetase inhibitor were studied in guinea pigs after performing mesenteric arterial occlusion. In this study, while ZK 36374 significantly lowered the alkaline phosphatase and creatine phosphokinase values two hours after mesenteric arterial occlusion when compared with the control group (p less than 0.005), UK 38485 did not induce any change. In guinea pigs, when given together, ZK 36374 and UK 38485 lowered the enzyme levels to preligation values and the difference was nonsignificant (p greater than 0.1). The histopathologic investigation of the small intestine after giving ZK 36374 and UK 38345 together revealed minimal changes. These findings stress the importance of preserving the PGI2 levels in the PGI2/TXA2 ratio in preventing the increase of lysosomal enzyme levels and histopathologic changes after mesenteric arterial occlusion in guinea pigs.

Nicardipine reduces the levels of leukotriene C4 and prostaglandin E2, following different ischemic periods in rat brain tissue.

Ischemic depolarization of nerve membranes is associated with a rapid influx of calcium into the cell, resulting in production of arachidonic acid (AA) metabolites. These metabolites, particularly leukotriene C4 (LTC4) have a very potent vasoconstrictor effect on cerebral arteries inducing vasogenic edema that may damage the ischemic penumbra. Calcium antagonists are assumed to prevent or reduce metabolic disturbances associated with ischemia. In this study, after developing an experimental animal model simulating the concept of the ischemic penumbra in the rat, the levels of LTC4 and prostaglandin E2 (PGE2) produced in the forebrain following different ischemic periods, such as 4th, 15th, 60th and 240th min were measured by a bioassay method, including 6 rats for each ischemic group. Then the effect of the 1-4 dihydropyridine nicardipine (1 mg/kg) on these mediators was investigated by giving it to the rat 30 min before the development of the ischemic model in each corresponding group (n = 6). We showed that nicardipine significantly reduced the high levels of LTC4 and PGE2 in the 4th min and 4th h of cerebral ischemia (p less than 0.005, p less than 0.0005). So it may be concluded that institution of nicardipine may be helpful in protecting the ischemic penumbra during the early hours of cerebral ischemia.

Role of endogenous endothelin peptides in intestinal ischemia-reperfusion injury in rats.

In this study, the effects of BQ123 (an ET(A) receptor antagonist), bosentan (a nonselective ET(A)-ET(B) antagonist), and phosphoramidon (an endothelin converting enzyme inhibitor) were investigated on intestinal mucosal lesion formation and changes in tissue PGE2 and LTC4 levels due to intestinal ischemia-reperfusion (I/R) injury in rats. Following 30 min of ischemia, the substances were given via the inferior caval vein, and 10 min later the intestine was subjected to reperfusion for 30 min. The intestinal specimens were evaluated both microscopically and the tissue PGE2 and LTC4 levels were obtained for each group. The histopathologic examination revealed a significant reduction in tissue injury in both BQ123 and phosphoramidon pretreated groups compared with the control group. Bosentan, on the contrary, did not decrease the injury. The pharmacologic examination revealed a significant reduction of PGE2-like activity in both BQ123 and phosphoramidon pretreated groups, compared with the control group, while LTC4-like activity remained unchanged except for an increase in the bosentan pretreated group.

The effect of Iloprost (ZK 36374) on isolated and transplanted pancreatic islet cells.

Several methods have been described for the prolongation of survival of isolated and transplanted islet cells. To investigate the effect of a stable prostacyclin analogue, ZK 36374 (Iloprost) on isolated and allotransplanted islet cell function, we studied 6 groups of rats: Group 1 (n = 7) animals underwent pancreatectomy and their islets were isolated and cultured by standard techniques. Group 2 (n = 8) animals were treated the same, except for the addition of Iloprost to the culture solutions. Group 3 (n = 7) animals were treated as group 1, but the isolated islets were transplanted to the subcapsular space of the left kidney of group 5 (n = 7) animals. Group 4 (n = 8) animals were treated as group 2, and the isolated islets were transplanted to group 6 (n = 8) animals. The insulin levels in the culture media obtained in group 1 and 2 were measured. In groups 5 and 6 blood glucose levels were measured and intraperitoneal glucose loading tests were performed. Histological examination was performed for both isolated and transplanted islets. The results showed that both insulin levels and histologic evaluation were better for group 2 than group 1. Animals in group 6 reached normoglycemia on the fifth day following transplantation while it was the ninth day for group 5. The intraperitoneal glucose loading test was tolerated better by group 6 animals. We conclude that Iloprost may be responsible for the improved results which seem to be due to its cytoprotective effect.

Does PGE2 act as a mediator for endothelin release?

To investigate the effect of iloprost (ZK 36374) and thromboxane synthetase inhibitor UK 38485 on endothelin release by the intestinal vascular endothelium after ischemia/reperfusion (IR) injury, five experimental groups were formed. The groups consisted of sham, control, iloprost treated (ILO), UK 38485 treated (TSI), and iloprost + UK 38485 treated (ILO + TSI) groups. The last three groups received the corresponding agents and then the superior mesenteric artery was clamped for 30 min followed by 90 min reperfusion. Endothelin levels in the portal blood and malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) levels in the intestinal tissue were determined. The MDA levels increased significantly in the control group and this increase was reversed in ILO, TSI, and ILO + TSI groups, the two drugs together showing a synergistic effect in preventing lipid peroxidation. The changes in the LTC4 levels were not significant among the groups. The increased endothelin levels in the control group were reversed in ILO and TSI groups but these two agents did not have a synergistic effect. Increased PGE2 levels were reversed with iloprost but neither UK 38485 nor the combination of the two agents was effective in decreasing PGE2 levels. It is concluded that endothelin release after mesenteric IR injury is relatively unrelated to lipid peroxidation and the lipoxygenase pathway. The cylooxygenase pathway has a direct effect on endothelin release and PGE2 may act as a mediator.

Prostaglandin E2 and leukotriene C4 levels following different reperfusion periods in rat brain correlated with morphological changes.

Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) are the metabolites of arachidonic acid (AA) that increase in forebrain following global ischemia and reperfusion. These mediators are highly potent vasoconstrictors of cerebral arteries leading to enhanced vascular permeability that induces the formation of vasogenic edema. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of PGE2 and LTC4 produced in the forebrain were measured and the effects of these mediators in short duration and prolonged reperfusion were investigated and then correlated with neuropathological findings. We found statistically significant reduction both in PGE2 and LTC4-like activities after just 10 min ischemia (p less than 0.05, p less than 0.05). PGE2-like activity significantly increased in the 4th and 60th min of reperfusion (p less than 0.05, p less than 0.05). In the 15th min of reperfusion, PGE2 was found to be significantly reduced (p less than 0.005) that may be due to the formation of free oxygen radicals by activation of PG hydroperoxidase reaction that inhibits PGE2 production in the cyclooxygenase pathway. LTs were not significantly increased in any reperfused group. Inhibition of the lipoxygenase pathway of AA metabolism may occur as a result of 15-HPETE (15-hydroperoxyeicosatetraenoic acid) production. Pathologically, edema and degeneration of brain tissue were seen beginning from the 4th min of reperfusion that reached a peak in the 60th min of reperfusion which is in accordance with biochemical changes in the damaged tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes.

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid (AA). They constrict blood vessels and enhance vascular permeability inducing vasogenic edema that may hurt the ischemic penumbra after cerebral ischemia and reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most potent inhibitor of 5-lipoxygenase in different tissues. Furthermore, it has considerable inhibitory activity against cyclooxygenase. In this study, after developing a global ischemic model in the rat, the levels of LTC4 and PGE2 in the forebrain were measured, following different reperfusion periods after 10 min ischemia including 8 rats for each reperfused group. Sham operations were performed for each corresponding control group (n = 8). AA metabolites were then correlated with neuropathological findings. In the combined reperfused groups both metabolites increased significantly when compared with 10 min, ischemic group (P < 0.05). In the 8 min reperfused group, PGE2 and LTC4 increased significantly compared with each corresponding control group (P < 0.005). These mediators also increased to high levels compared with the 4 min reperfused group (P < 0.05, P < 0.005). PGE2 and LTC4 were reduced significantly at the 15th and 60th min of reperfusion compared with the 8 min reperfused group (P < 0.05, P < 0.005). NDGA (0.1 mg/kg) reduced both metabolites in the 8 min reperfused group significantly (P < 0.05). Brain cortex specimens were taken for light and electromicroscopical investigations. No significant differences were noted between the structural changes in the 4, 8 and 15 min of reperfusion and NDGA administered groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue.

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.

The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver.

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.