Dynamic Thiol/Disulphide Homeostasis in Acute Urticaria.

BACKGROUND: Urticaria is an unknown, sudden, and itchy skin disease that is recognized with redness, swelling, and is sometimes seen with angioedema. It is classified as acute or chronic, depending on the duration of symptoms. Thiols in plasma are powerful antioxidants that physiologically eliminate free radicals. The mostly and rapidly affected proteins are thiols that contain the sulfhydryl group. In the present study, the thiol/disulfide homeostasis was investigated as a brand new indicator of oxidative stress in patients who had acute urticaria and presented to the emergency department. OBJECTIVE: In the present study, the thiol/disulfide homeostasis, ischemia-modified albumin (IMA), and and neutrophil lymphocyte ratio (N/L ratio) were investigated in the etiopathogenesis of acute urticaria. MATERIAL AND METHOD: A total of 37 patients and 40 healthy volunteers were included in the study. Thiol/disulfide homeostasis (TDH) [total thiol-native thiol/disulfide changes] was measured in both groups (patient group and control group) using a brand novel method developed by Erel and Neselioglu. Half of the difference between total thiol and native thiol concentrations gives the amount of disulfide bond. RESULTS: Total thiol and native thiol levels in blood were found to be low. The levels of total thiol (P = 0.218) and native thiol (P = 0,001) were significantly lower in patients with acute urticaria than in the control group. At the same time, the level of disulfide was significantly higher in the patient group than in the control group (P = <0.001). The level of IMA was higher in the patient group than in the control group (P < 0.001). CONCLUSION: While total thiol and native thiol are low in acute urticaria, the levels of disulfide and IMA are high.

Effect of topical insulin on cutaneous wound healing in rats with or without acute diabetes.

BACKGROUND: Diabetes is a condition known even in its early stages to impair the normal course of wound healing, thus leading to chronic wounds. The role of insulin in the regulation of energy metabolism, protein synthesis, cell differentiation and growth suggests that this hormone could also play an essential role in regulation of wound healing. AIM: To determine the effects of topical insulin administration on wound healing in rats with or without acute diabetes. METHODS: This study was conducted using four groups of male Sprague-Dawley rats: (i) nondiabetic rats receiving topical insulin (n = 7), (ii) nondiabetic rats receiving topical sterile water (n = 7), (iii) diabetic rats receiving topical insulin (n = 7) and (iv) diabetic rats receiving topical sterile water (n = 7). Wound healing was assessed by wound contraction rate, complete epithelialization time and histological results. RESULTS: Topical insulin enhanced wound healing by shortening the time needed for complete epithelialization in both the nondiabetic and acute diabetic groups. The histological observations supported the planimetric results in both groups. CONCLUSIONS: This study revealed that topical insulin application to cutaneous wounds accelerates wound healing in rats with or without acute diabetes.

Accelerated forgetting and verbal memory consolidation process in idiopathic nondement Parkinson's disease.

OBJECTIVE: Episodic memory impairment and underlying pathophysiology in Parkinson's Disease (PD) is poorly investigated. Formerly, it was thought to be a secondary effect of impairment in fronto-striatal circuit. However, recent studies hypothesized that there is a dual progression of PD and memory loss is possibly related to posterior cortex rather than frontal. To understand the impairment, underlying mechanisms should be investigated. Although consolidation is one of these mechanisms consolidation phase of episodic memory in PD was not investigated yet. Recently accelerated long term forgetting (ALF) phenomenon is emphasized in consolidation researches. METHOD: Here it is evaluated the presence of accelerated long-term forgetting in nondemented PD as a consequence of a deficit in consolidation process. 32 patients and 33 controls participated in the study. Turkish Verbal Memory Process Test (VMPT) was applied to both groups. Delayed recall (DR) scores collected after 30 min, one week and six weeks. Forgetting rates were calculated based on these scores. RESULTS: There was significant difference in DR scores of patients compared to controls in the 30th minute and sixth week. Forgetting rate between 30th minute-1st week did not differ but 1st-6th week was found statistically significant across groups. CONCLUSIONS: To the best of our knowledge, this is the first study investigating verbal memory consolidation in PD. Results suggested that impairment is possibly related to the late phase of consolidation of verbal memory in neocortex.

Changes in kidney tissue and effects of erythropoietin after acute heart failure.

Impairment of cardiac function causes renal damage. Renal failure after heart failure is attributed to hemodynamic derangement including reduced renal perfusion and increased venous pressure. One mechanism involves apoptosis and is defined as cardiorenal syndrome type 1. Erythropoietin (EPO) is a cytokine that induces erythropoiesis under hypoxic conditions. Hypoxia inducible factor 1 alpha (HIF-1α) plays a regulatory role in cellular response to hypoxia. Protective effects of EPO on heart, kidney and nervous system are unrelated to red blood cell production. We investigated early changes in and effects of EPO on renal tissues of rats with myocardial infarction by morphology and immunohistochemistry. Coronary artery ligation was used to induce myocardial infarction in Wistar rats. Group 1 comprised sham operated rats; groups 2, 3 and 4 included rats after coronary artery ligation that were sacrificed 6 h after ligation and that were treated with saline, 5,000 U/kg EPO or 10,000 U/kg EPO, respectively; group 5 included rats sacrificed 1 h after ligation. Group 2 showed increased renal tubule damage. Significantly less tubule damage was observed in EPO treated groups. EPO and EPO receptor (EPO-R) immunostaining intensities increased slightly for group 5 and became more intense for group 2. EPO and EPO-R immunostaining was observed in the interstitial area, glomerular cells and tubule epithelial cells of EPO treated groups. HIF-1α immunostaining was observed in collecting tubules in the medulla only in group 2. Caspase-3 immunostaining is an indicator of apoptosis. Caspase-3 staining intensity decreased in renal medulla of EPO treated groups. EPO treatment may exert a protective effect on the renal tissues of patients with cardiorenal syndrome.

Determination of malondialdehyde, reduced glutathione levels and APOE4 allele frequency in late-onset Alzheimer's disease in Denizli, Turkey.

OBJECTIVES: The aim of the present study was to determine the Apolipoprotein E (APOE) 4 allele frequency of patients with late-onset Alzheimer's disease (AD) and to determine the effects of oxidant-antioxidant balance on AD. DESIGN AND METHODS: PCR-RFLP was undertaken in 62 cases with AD and 56 aged-matched controls. Activities of reduced glutathione (GSH) and malondialdehyde (MDA) concentration were measured in same groups. RESULTS: Patients with at least one E4 allele genotype were significantly different in patients with AD (21%) than controls (9%) (p=0.01). Serum MDA levels were significantly different between AD patients and Control group (p=0.0001). There was no significant difference in serum GSH levels between AD patients and C groups. CONCLUSION: These results confirmed that the APOE4 allele occurs frequently in late onset AD compared with normal controls. Also elevated MDA levels are likely an essential factor in the pathogenesis and neuronal damage of AD.

Effect of aging on the distribution of basic fibroblast growth factor immunoreactive cells in the rat hippocampus.

Hippocampal formation is extremely sensitive to the aging process and appears to be one of the first regions to show structural and physiological changes with advancing age. Basic fibroblast growth factor (bFGF) plays an important role in the stimulation of mitogenesis in glial cells, the support of neuronal survival and the promotion of neurite outgrowth in vitro. In the present study, the effect of aging on the distribution of bFGF immunoreactive (bFGF-ir) cells was investigated. The protein product of bFGF was visualized immunohistochemically in the dorsal hippocampus of Wistar albino rats. bFGF-ir astrocytes in different subfields of hippocampus and neurons in CA2 field were quantified to determine whether changes in immunoreactivity were correlated with advancing age. Aging was accompanied by a decrease in bFGF-ir cell density in subfields of hippocampus. We concluded that aging was associated with a reduction in bFGF-ir cell density that may reflect a decreased expression of bFGF in the rat hippocampus.

The effect of alpha-melanocyte stimulating hormone on endotoxin-induced intestinal injury.

We investigated the effect of alpha-melanocyte stimulating hormone (alpha-MSH) on endotoxin-induced intestinal inflammation and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally (i.p.); twice daily) reduced the severity of the lesions macroscopically and microscopically. This protective effect was found to be confined mainly to the distal ileum. These lesions were reversed by pretreatment with the non-selective COX inhibitor indomethacin (10 mg/kg, subcutaneously (s.c.)) but not by the selective COX-2 inhibitor nimesulide (3 mg/kg, s.c.), the NO donor sodium nitroprusside (4 mg/kg, i.v.) or the iNOS inhibitor dexamethasone (3 mg./kg, i.p.) at macroscopic level and reversed by Indo or Dex at microscopic level. Increased peroxidase activity -index of tissue neutrophil infiltration- in the distal ileum of LPS-treated rats was decreased by alpha-MSH and this effect was reversed by pretreatment with Indo. In conclusion, the neuropeptide alpha-MSH has a beneficial effect on endotoxin-induced distal intestinal lesions by a mechanism which probably involves nitric oxide and COX-1 derived prostaglandins.

The effect of alpha-melanocyte stimulating hormone on colonic inflammation in the rat.

The effect of alpha-melanocyte stimulating hormone (alpha-MSH) on colonic inflammation in the rat. In this study, we investigated the effects of alpha-MSH administration on trinitrobenzene sulfonic acid-induced colitis and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally; twice daily for 3 days) reduced the colonic macroscopic lesions compared to untreated ones in both acute and chronic colitis groups. This effect was reversed by pretreatment with the nitric oxide donor, sodium NP (4 mg/kg, intravenously) or cyclooxygenase-1 selective antagonist indomethacin (5 mg/kg, subcutaneously) in the acute group and with the cyclooxygenase-2 selective antagonist nimesulide (3 mg/kg, subcutaneously) in the chronic group. alpha-MSH had no effect on colonic wet weight and myeloperoxidase activity compared to the untreated colitis group. However, protein oxidation was markedly elevated in the alpha-MSH-treated group compared to untreated ones. Nitroprusside and indomethacin reversed the effect of alpha-MSH on macroscopic lesions in the acute groups, whereas nimesulide showed a similar effect in the chronic group. In conclusion, the results of our study show a protective role of alpha-MSH on colonic lesions which partially involves nitric oxide and prostaglandins.

The protective effect of melatonin on cisplatin nephrotoxicity.

Regarding the mechanisms of cisplatin (CP) nephrotoxicity, several hypotheses have been put forward, among which oxidative stress (including depletion of glutathione and production of lipid peroxide) is noticeable. This investigation elucidates the role of the antioxidant system in CP-induced nephrotoxicity and the nephroprotection by melatonin. Balb/c mice were injected i.p. with: 1) vehicle control; 2) a single dose of 6.5 mg/kg cisplatin, CP group; 3) melatonin in a dose of 10 mg/kg for 5 days after CP injection, CP-M group; 4) melatonin (10 mg/kg) for 5 days before and after CP injection, M-CP-M group; 5) melatonin in a dose of 10 mg/kg for 5 days, M group. Mice were sacrificed 5 days after CP injection to determine blood urea nitrogen (BUN) and serum creatinine. Renal lipid peroxidation (LP) and glutathione (GSH) levels were evaluated in kidney homogenates. Cisplatin administration resulted in increased LP, BUN and serum creatinine levels and decreased GSH levels, whereas melatonin reversed these effects. Morphological kidney damage was apparent in the CP group. Mentioned degeneration was moderate in the CP-M group, whereas morphological findings of the M-CP-M group implied a well preserved kidney tissue. When M was administered alone, it didn't cause any significant change in biochemical parameters. Both C and M groups exhibited similar biochemical and morphological findings in light and transmission electron microscope observation. In conclusion, the present study suggests that melatonin may be of therapeutic benefit when used with CP.

Beneficial effects of glycocholic acid (GCA) on gut mucosal damage in bile duct ligated rats.

In order to investigate the effect of bile acids on gastrointestinal inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral or colonic) or saline I h before ethanol challenge and twice daily for 3 days in the ileitis group, while GCA was given twice daily for 3 days in the colitis group. BDL reduced the macroscopic and microscopic damage scores in the ileitis group compared to sham operated group, while it had no significant effect on ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index and microscopic damage in colitis group compared to saline-treated groups, but had no effect in ileitis group. Both BDL and GCA administration in BDL group reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration in BDL group inhibited gastric acid output and volume. Our results suggest that oral or colonic administration of primary bile acids may be useful for the treatment of gastrointestinal inflammations.

Effects of preservation of rat lungs in a hypothermic medium on alveolar morphology.

The increasing use of organs such as liver, lung, heart, pancreas, kidney and small intestine for transplantation purposes necessitates the development of optimum preservation techniques. The aim of our study was to investigate time-related morphological changes in alveoli during preservation of rat lungs in hypothermic Euro-Collins solution. Lungs were perfused via the pulmonary arteries with Euro-Collins solution at a temp of 19 degrees C. Totally perfused lungs were placed in Euro-Collins solution and stored for 6, 12 and 24 h at 4 degrees C. Biopsies were taken and prepared for examination at the light and electron microscopical level. Light microscopic examination revealed good preservation of the alveoli after storage for 6 h and moderate damage of alveolar architecture after 12 h of preservation. Severe degeneration of alveoli was found after 24 h of storage. The main ultrastructural changes were observed in lungs stored for 12 h and 24 h. After 6 h of storage, tissue damage was not found. Pneumocytes type II lost their apical microvilli and lamellar bodies were electron-lucent, indicating lamellar degeneration after 12 and 24 h of storage. Pneumocytes type I were also damaged. Their cytoplasm contained many vacuoles. Endothelial lining of the capillaries was contracted. Endothelial cells also showed many vacuoles. Edema around the capillaries was observed. We conclude on the basis of our morphological study, that Euro-Collins solution at low temperature is a good preservative for a short period of time only, but serious tissue damage occurs after periods of preservation longer than 12 h.

Acute lung injury following thermal insult to the skin: a light and transmission electron microscopial study.

Oxygen radicals are involved in the development of burn shock and distant organ injury in animal models of trauma. Neutrophils are likely the source of reactive oxygen metabolites as a result of the systemic inflammatory reaction to a local burn insult. The aim of the present study was to assess the role of neutrophils in the development of lung injury related to second degree skin burn in rats. Rats were decapitated at two hours following burn injury. Lung tissue samples were removed and examined biochemically and histologically. Tissue-associated myeloperoxidase (MPO) activity, which is an index of neutrophil infiltration, was increased considerably in lung tissue at 2 h after burn injury. Disturbance of alveolar structure, intraalveolar hemorrhage and prominent neutrophil infiltration indicated lung parenchymal injury. Ultrastructural examination of the lung revealed that pneumocytes type I, pneumocytes type II and capillary endothelial cells were degenerated. The data presented here suggest that neutrophil accumulation in the lung is involved in pathogenesis of this distant organ after burn injury.

The effect of CO2 insufflation rate on the postlaparoscopic shoulder pain.

Shoulder pain (SP) is frequently mentioned in recent literature following laparoscopic operations. In the literature, many causes have been declared to explain shoulder pain after CO2 insufflation, such as direct peritoneal irritation of the CO2 gas, excessive traction of the triangular ligament, and overstretching of the diaphragmatic muscle fibers due to the high rate of insufflation. This study was planned as multicentric, and 76 patients, aged between 35 to 45, were entered into the study. They were all selected by a randomized sampling method, with equal numbers of men and women, to achieve true evaluation. The low flow-rate (LFR) group was insufflated with 2.5 L/min and the high flow-rate (HFR) group with 7.5 L/min. All cases were evaluated by subjective pain classification on postoperative day 3. According to the subjective pain scale method, shoulder pain average was 23.9+/-3.1 in the LFR group and 55.4+/-6.5 in the HFR group. The difference between these groups was significant (p > 0.01). There is no significant difference for the operation time (LFR%: 64+/-15 minutes, HFR: 61+/-20 minutes, p > 0.05). Our results suggest that there is a significant statistical relation between the postoperative shoulder pain levels and increased insufflation rates. For this reason, low insufflation rate significantly reduces the shoulder pain but does not increase the operation time. Therefore, a low insufflation rate should be applied in all cases for patients' comfort and safety.

Thyroidectomy with and without drains.

Drainage after thyroid surgery has been widely used to prevent life-threatening complications. However, it is well known that drains do not always prevent haematoma formation. In this retrospective study, we reviewed our experience with 1057 thyroidectomies with and without drains in order to assess this issue. Between 1983 and 1993, 520 patients were closed with drains and 537 patients without drains after thyroid surgery. The indications for drainage of the selective period included wet operative field and large areas of dead space at the conclusion of the operation. Reoperation for bleeding was done in twelve patients in the drainage group and two patients in the non-drainage group (p < 0.05). Wound infection was seen in seven patients in the drainage group and none in the no-drainage group (p < 0.05). This study suggests that routine drainage after thyroid surgery is not necessary and a selective policy can be applied safely.

Vascularization of the long flexor tendon.

The arterial supply of the long flexor tendon of the index and ring fingers were studied morphologically on 36 cadaver hands. Our studies, showed that the long flexor tendons were supplied by two main sources. Primarily by small arteries which ran in the vinculum longum and vinculum brevis and reached the dorsal surface of the tendon. Also by small intrinsic longitudinal vessels which ran parallel to the collagenous fibers of the tendon and extended from the muscular attachment of the long flexor tendons. No morphological difference on the vascularization of the index and ring fingers were observed.

A morphological study on the V2 segment of the vertebral artery.

Morphometric investigations on the V2 segment of the vertebral artery, showed that, it did not have a constant calibre during its course within the foramina transversaria. The vertebral artery, entering the foramina transversaria reduced its calibre and further continued to reduce until C3 level, above C3 it began to reincrease its calibre and at C1 level reached its largest calibre. Measurements on the muscular thickness, showed an increase as ascending through the foramina transversaria. The widening and narrowing of the vertebral artery within the foramina transversaria was attributed as tortious artery or congenital anomaly. This study showed that it was the normal anatomy of the artery within the foramina transversaria.

Risk for malignant and borderline ovarian neoplasms following basic preoperative evaluation by ultrasonography, ca125 level and age.

OBJECTIVE: To verify the basic preoperative evaluation in the discrimination between benign and malignant adnexal masses in our clinical practice. MATERIALS AND METHODS: Data were collected on the records of 636 women with adnexal masses who had undergone surgery either by open or endoscopic approaches. Those with obvious signs of malignancy, any history of cancer, emergency surgeries without basic evaluation were excluded. The preoperative features by age, ultrasound and serum Ca125 level were compared with final histopathological diagnosis at the four departments of the institution. These are the general gynecology (Group 1: exploratory laparotomy), the gynecologic endoscopy (Group 2: laparoscopy and adnexectomy), the gynecological oncology (Group 3: staging laparotomy) and the gynecologic endocrinology and infertility (Group 4: laparoscopy and cystectomy). RESULTS: There were simple and complex cyst rates of 22.3% and 77.2%, respectively. There were 86.3% benign, 4.1% (n:20) borderline ovarian tumor (BOT) and 6.4% (n:48) malignant lesions. There were 3 BOT and 9 ovarian cancers in Group 1 and one BOT and two ovarian cancer in the Group 2. During the surgery, 15 BOT (75%) and 37 ovarian cancer (77%) were detected in the Group 3, only one BOT was encountered in the Group 4. The risk of rate of unsuspected borderline or focally invasive ovarian cancer significantly increased by age, size, complex morphology and Ca125 (95% CI, OR=2.72, OR=6.60, OR=6.66 and OR=4.69, respectively). CONCLUSIONS: Basic preoperative evaluation by comprehensive ultrasound imaging combined with age and Ca125 level has proved highly accurate for prediction of unexpected malignancies. Neither novel markers nor new imaging techniques provide better information that allow clinicians to assess the feasibility of the planned surgery; consequently, the risk of inadvertent cyst rupture during laparoscopy may be significantly decreased in selected cases.

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats.

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.

The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder.

Oxytocin (OXY), a well-known nonapeptide, plays a crucial role in reproduction, and has effects on modulating the immune and inflammatory processes in living organisms as well. Recently it is also known as an antioxidant in several organs. The present study aims to demonstrate the protective effect of OXY against ischemia/reperfusion (I/R) injury in urinary bladder tissue. Abdominal aorta of rats, were clamped to perform urinary bladder ischemia. OXY (0.5 µg/kg) was injected intraperitoneally before ischemia in I/R+OXY group, whereas the vehicle solution was injected to I/R group. At the end of reperfusion, tissue samples from urinary bladder were processed for histochemical, ultrastructural and biochemical analysis. Tissue sections were stained by toluidine blue for mast cell counting and hematoxylin-eosin for histopathology. In addition, malondialdehyde (MDA) and glutathione (GSH) levels were determined biochemically. The results demonstrated that there was an extreme damage at urothelium, dilatation of intercellular junctions, inflammatory cell infiltration in I/R group. I/R+OXY group demonstrated a reduction in the severity of urinary bladder damage. According to mast cell counting results, both granulated and degranulated mast cells were decreased in I/R+OXY group compared to I/R group. The mean MDA level was higher in I/R group compared to control and lower in I/R+OXY group compared to I/R group. GSH level reduced in I/R group compared to the control and increased in I/R+OXY group compared to I/R group. In conclusion, oxytocin, as confirmed by histological evaluation and biochemical assays has a potential protective effect in the urinary bladder tissue against ischemia/reperfusion injury.

A comparative ontogenic study of urinary bladder: impact of the epithelial differentiation in embryonic and newborn rats.

The present study aimed to show the cellular and subcellular distribution of glycogen content during the differentiation of urothelial cells from simple cuboidal to stratified transitional epithelium. Bladder samples were taken from rat embryos on the 15th to 19th days and newborn at 21st day. During the development of the bladder, the formation of fusiform vesicles, asymmetric unit membrane (AUM) and microridges were examined with staining with haematoxylin-eosin and periodic acid Schiff for light microscope and periodic acid-thiocharbohydrazide-silver proteinate for transmission electron microscope. The topographical changes of luminal differentiation were examined with the scanning electron microscope. The urothelium was simple cuboidal from 15th till the 17th days of gestation. Glycogen content was present in the cytoplasm till the 18th day of gestation. At the early stage (16th day) of gestation, the apical surface contains microvilli that points the undifferentiated cells. The density of microvilli decreased and ropy microridges appeared at the 17th day of gestation. The small discoid vesicles lined with AUM developed at the apical cytoplasm of the surface cells at the 17th day of gestation. After this stage, both the density of microridges and large and elongated fusiform vesicles increased. The differentiation of the urothelium begins with the formation of the round and small vesicles, continues with the formation of the AUM and at the final stage there is a decrease in both glycogen content and the appearance of the microridges at the luminal surface of the urothelial cells.