Melatonin: a hepatoprotective agent against radioiodine toxicity in rats.

OBJECTIVES: The aim of the current study was to investigate the possible radioprotective effects of melatonin against hepatic radioiodine (RAI) toxicity. METHODS: Thirty-six rats were randomly divided into three groups: untreated control (Group 1); oral radioiodine (RAI, 111 MBq) administrated rats (Group 2), and melatonin group (oral RAI and daily intraperitoneal injection of 12 mg/kg melatonin-Group 3). In the third group, melatonin administration was started two days before and continued for five days after RAI administration. Twenty-four hours after the administration of the last dose of melatonin, liver samples were taken for biochemical and histopathological evaluation. RESULTS: Oxidative stress parameters demonstrated that melatonin treatment decreased the tissue malondialdehyde (MDA), advanced the oxidation protein products (AOPP) levels, and increased the total-SH (sulphydryl) levels when compared with RAI group. The differences were statistically significant between these groups for all parameters (p < 0.05). The histopathological damage in the melatonin-treated group was significantly less than the damage in RAI group (p < 0.05 for all pathological parameters). CONCLUSION: The results of this study demonstrated that melatonin reduced the harmful effects of RAI treatment on the liver. Anti-inflammatory and antioxidant activities are likely to be involved in the mechanism underlying the radio-protective effects of melatonin (Tab. 3, Fig. 1, Ref. 30).

Evaluation of intraabdominal adhesion generating potentials of ankaferd and calcium alginate used as hemostatic agents.

AIM: The present study aimed to evaluate intra-abdominal adhesion generating potential of Ankaferd Blood Stopper (ABS), which was used as postoperative hemostatic agent in the rats that underwent surgery, in comparison with Ca-alginate. MATERIAL AND METHOD: Totally, 30 rats were randomized into 4 groups. In the control group, 1x1 cm peritoneum was removed from the right lower quadrant after cecal abrasion. In the other two study groups, the same procedure was performed after Ankaferd Blood Stopper and Ca-alginate application respectively. RESULTS were evaluated both histopathologically and by adhesion scoring methods. All results underwent statistical analysis. RESULTS: Comparing overall results, no statistically significant difference was found between the sham, control, ABS and Ca-alginate groups (p = 0.099). Paired group comparisons revealed no statistically significant difference between the sham group and the control, ABS, and Ca-alginate groups (p = 0.222, p = 0.222, and p = 0.833 respectively). It was observed that there was no statistically significant difference between the control and ABS groups (p = 0.505), but there was a statistically significant difference between the control and Ca-alginate groups with Bonferroni correction (p = 0.028). Histopathological examination revealed no statistical difference between the groups. CONCLUSION: In conclusion, intra-abdominal adhesion generating potentials of Ca-alginate and ABS were experimentally evaluated and macroscopic and microscopic comparisons revealed no significant difference between sham, control, Ca-alginate, and ABS groups (Fig. 8, Ref. 36). Text in PDF www.elis.sk. agent.

Increased number of multi-oocyte follicles (MOFs) in juvenile p27Kip1 mutant mice: potential role of granulosa cells.

STUDY QUESTION: Why are female mice that lack a functional p27 protein infertile? SUMMARY ANSWER: The absence of a functional p27 leads to a dramatic increase in the number of multi-oocyte follicles (MOFs) in juvenile female mice; p27 would promote the individualization of follicles favoring the development of fertile eggs. WHAT IS KNOWN ALREADY: p27-/- female mice are infertile. p27 suppresses excessive follicular endowment and activation and promotes follicular atresia in mice. MATERIALS AND METHODS: Ovaries from wild type (WT) and p27Kip1 mutant mice aged 2, 4 and 12 weeks were subjected to immunohistochemistry/immunofluorescence. The slides with whole organs serially sectioned were scanned and examined by image analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with WT, p27Kip1 mutant pre-pubertal mice had a greater number of oocytes, a greater number of growing follicles and a greater number of MOFs. These differences were statistically significant (P < 0.05), particularly in the case of MOFs (P > 0.001). The unusually large number of MOFs in juvenile p27-deficient mice is a novel observation. In WT mice p27 protein remains present in the oocyte nucleus but gradually decreases in the ooplasm during follicular growth, while granulosa cells show dynamic, follicle stage-related changes. LIMITATIONS, REASONS FOR CAUTION: These results have been obtained in mice and they cannot be directly extrapolated to humans. WIDER IMPLICATIONS OF THE FINDINGS: The dramatic increase in the numbers of MOFs in juvenile p27 mutants has not been previously reported. The number of MOFs declines sharply as the mice become sexually mature, pointing to their negative selection. These findings open a new approach to the study of sterility. STUDY FUNDING/COMPETING INTERESTS: This study has been funded by the Basque Government, Dept. of Health grant 2007111063 and Dept. of Industry (Saiotek) grant S-PC11UN008. Jairo Perez-Sanz was the recipient of a grant from Fundación Jesús de Gangoiti Barrera. The authors have no conflicts of interest to declare.

Effects of diosmine-hesperidine on experimental colonic anastomosis.

AIM: Our goal was to determine the effects of a diosmine-hesperidine combination on wound healing in a rat model of colonic anastomosis. MATERIALS AND METHODS: In this study, 20 Wistar Albino female rats were randomized into four experimental groups containing five rats in each group. A segment of 1 cm of colon was excised 4 cm proximally to the peritoneal reflection in all rats without carrying out any mechanical or antibacterial bowel preparation. Colonic anastomosis was performed with interrupted, inverting sutures of 6/0 polypropylene. Beginning from the first postoperative day, the rats in Groups II and IV received 100 mg/kg per day of diosmine-hesperidine via orogastic route by 4F fine feeding catheter. RESULTS: A significant difference was detected between groups in terms of their hydroxyproline levels (p<0.05); the hydroxyproline level of Group I was significantly lower than that of the other groups while no significant difference was noted between Groups II and III. CONCLUSION: The administration of diosmine-hesperidine increased the amount of collagen and bursting pressures at the anastomotic site and thus had favorable influences on the healing of colonic anastomosis (Tab. 1, Fig. 3, Ref. 33).

Vascular programming in twins: the effects of chorionicity and fetal therapy for twin-to-twin transfusion syndrome.

We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case-control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.

Advanced donor age alone is not a risk factor for graft survival in kidney transplantation.

BACKGROUND: The use of kidneys from elderly deceased donors has substantially increased organ supply, although it is associated with worse graft function and survival rates. The risk of kidneys from elderly donors as well as expanded criteria donors (ECDs) on kidney transplant outcome was investigated. PATIENTS AND METHODS: Seventy-five kidney transplants from ECDs over a 5-year period were reviewed retrospectively. Old age and increased donor risk variables were analyzed separately in relation to graft function and survival. RESULTS: Sixty-four of 75 (85.3%) recipients had functioning grafts 5 years posttransplant. The overall actuarial graft survivals from 1 to 5 years were 87.5%, 68.1%, 57.3%, 55.4%, and 47.3%, respectively. Early graft function gave 47 (62.7%) kidneys remarkable actuarial survivals of 100.0%, 88.3%, 75.8%, 75.8%, and 68.4% at 1 to 5 years posttransplant, and 28 (37.3%) kidneys had delayed graft function with substantially decreased actuarial survival rates, ranging from 66.7% to 23.2%. Kidneys from elderly donors had considerable actuarial graft survival rates of 100.0%, 83.3%, 76.9%, 76.9%, and 67.0% from 1 to 5 years, respectively; these were the best graft survival rates compared with kidneys from the other donor categories. The other donor risk variables when associated with advanced age of any had an adverse effect on recipient graft function and survival, but no single risk variable alone, or a combination of any two, showed any statistically significant variability. CONCLUSION: Elderly kidney donors provided a substantial organ pool expansion without affecting patient and graft survival in many patients. ECDs can be utilized safely if adequate measures are taken.

Pseudoaneurysm of the left gluteal artery after a pelvic fracture sustained during the Marmara earthquake: report of a case.

Although iliac artery injuries caused by pelvic fractures are uncommon, in special circumstances, such as earthquakes, traumatic arterial injury should be carefully investigated. This reports describes a case of an iliac artery pseudoaneurysm causing compressive symptoms that was successfully treated by radiologic embolization.

Renovascular actions of adenosine in the isolated perfused rat kidney: possible underlying mechanisms.

We studied the renovascular action of adenosine on isolated perfused rat 10 min after drug injections. Adenosine was applied intraarterially as a single bolus injection in logarithmically increasing doses (0.3-30 microg). Adenosine treatment induced a biphasic vascular-response, namely, an initial vasoconstriction followed by a long-lasting vasodilation. Pretreatment with 0.1. 0.3, or 1.0 mM theophylline or quinidine (2 microg/ml) significantly depressed both components of the adenosine response. The vasoconstrictor response to adenosine was not affected by either 0.5 or 1.0 microg/ml dihydroergocristine. whereas the vasodilatory response was dose-dependently reduced. The biphasic response to adenosine was markedly depressed by 10 microg/ml indomethacin and was augmented by combining this agent with quinidine. We studied the possible roles of the platelet activating factor (PAF) and nitric oxide-cGMP systems in the renovascular actions of adenosine. Tebokan (a PAF antagonist) antagonized both components of the response, but methylene blue (MM) reduced only the pressory part Electron-microscopic examination of kidneys exposed for 15 min to MM showed some acute degenerative alterations and constriction in the glomeruli. From these findings, we conclude that the P1/A1, and P2x purinoceptors, the prostaglandins, PAF, and the NO-cGMP systems have a share in the renovascular actions of adenosine.

On the mechanisms of adenosine induced pulmonary vasoconstriction in rats.

The effect of adenosine on pulmonary vessels was studied in isolated perfused rat lungs. Drugs were administered intra-arterially in a fixed volume of 0.1 ml Krebs solution as bolus injections. Adenosine responses were obtained before and 10 min after drug injections. When applied in logarithmically increasing doses (1-100 micrograms/ml), adenosine caused dose-dependent increases in pulmonary perfusion pressure (e.g. pulmonary vasoconstriction) which were readily reversible. Challenging adenosine with quinidine, dihydroergocristine and cyproheptadine (2 micrograms/ml each) did not significantly alter adenosine responses. Pretreatment of lungs with 0.5 mM theophylline, 10 micrograms/ml indomethacin, 30 micrograms/ml tebokan (a PAF antagonist) or 1 microgram/ml methylene blue for 10 min, however, antagonized the vasoconstrictor effect of the drug significantly. From these experiments, it was concluded that the mechanisms underlying the pulmonary vasoconstrictor action of adenosine are complex, and that both types of purinoceptors, prostaglandins, PAF and other vascular endothelial hormones might be involved.

Penetration of ciprofloxacin into pleural fluid.

The penetration of oral 1000 mg/day ciprofloxacin into pleural fluid is investigated in 15 patients with exudative pleural effusion. After 4 days of ciprofloxacin therapy ciprofloxacin concentrations were measured in plasma and pleural exudate simultaneously by high-performance liquid chromatography (HPLC). Mean serum ciprofloxacin level was 1.58 +/- 0.91 mg/L and mean pleural exudate concentration was 1.00 +/- 0.59 mg/L. The concentrations achieved were all above the MIC90 of the majority of Gram-positive and Gram-negative pathogens. It is concluded that ciprofloxacin penetrates well into the pleural fluid.

Venous blood histamine levels and effect of terfenadine in patients with bronchial hyperreactivity.

Twenty-two subjects complaining of cough, chest tightness and/or shortness of breath with normal chest radiograph and normal pulmonary function test results were challenged with methacoline. Venous histamine levels were measured before and just after methacoline challenge. For comparison, a single blood sample was obtained from 10 normal subjects. Blood histamine levels were significantly higher in subjects with respiratory symptoms regardless of methacoline challenge being positive or negative (p less than 0.001). After methacoline challenge, blood histamine increased significantly in methacoline challenge positive group (p less than 0.05). Thereafter, terfenadine, a H1 antagonist, 120 mg/day were given to patients for one month. After terfenadine therapy, there was a subjective improvement of symptoms, methacoline provocation dose (PD20) increased and there was no significant change in blood histamine level. It is concluded that nonspecific challenge increases blood histamine levels and blood histamine levels seems to be a sensitive index of bronchial hyperreactivity in subjects with respiratory symptoms of unknown origin and that terfenadine is effective in the treatment of bronchial hyperreactivity.

Effect of theophylline in chronic obstructive lung disease.

The bronchodilator, respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease (COLD). The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day, serum theophylline concentration was negligible. Initial pulmonary function tests were performed. Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day. Ten of the patients were given placebo. On day 7, serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated. Bronchodilator effect was assessed by spirometry, flow-volume loops and measuring airway resistance (Raw). Respiratory muscle function was assessed by measuring maximal inspiratory (PImax) and expiratory pressures (PEmax) and the effect on respiratory center was evaluated by minute ventilation, mouth occlusion pressure index and inspiratory duty ratio. Forced vital capacity in one second (p less than 0.001), maximal mid expiratory flow rate (p less than 0.05), maximal expiratory flow at 50 percent of vital capacity (p less than 0.001), maximal inspiratory pressure (p less than 0.01) increased, while airway resistance (p less than 0.05) decreased significantly. Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy. In placebo group, there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures. It is therefore, concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease, increases respiratory muscle function, but in therapeutic doses has no effect on respiratory center.

Identification of thiol-activated T-kininogenases in the rat and mouse submandibular glands.

T-kininogen is a unique protein(s) which is directed for synthesis following inflammation such as that caused by adjuvant arthritis and carrageenin. The properties of the protein include thiol-protease inhibition and the potential to act as a substrate to release Ile-Ser-bradykinin (T-kinin). During the inflammatory response, free T-kinin is found in the blood and inflammatory fluids indicating that T-kininogenase (T-kgnase) enzymes exist that release T-kinin and perhaps related T-kinins involved in inflammation. We report here that T-kininogenases have been found in the rat and mouse submandibular glands and in rat peritoneal white cells. The pH optimum is about 8.0. The enzymes must be thiol-activated. Thus, the rat has the complete T-kgnase-T-kinin system. Since T-kininogen is a member of the superfamily of cysteine protease inhibitors, members of the superfamily may be directed for synthesis in inflammatory diseases including ascites in other species including humans.

Isolation of a thiol-activated T-kininogenase from the rat submandibular gland.

T-kininogenase (T-kgnase) activity has been investigated in tissues of the rat and submandibular glands of the rat, mouse and guinea pig. Both rat and mouse submandibular homogenates showed high T-kgnase activity. The enzyme has been purified 360-fold from rat submandibular gland homogenate supernatant fluid. The enzyme has an apparent molecular mass of 28 kDa and a pH optimum of 8.0 toward T-kininogen. It cleaved T-kininogen in catalytic quantities to release T-kinin (Ile-Ser-bradykinin) and small quantities of bradykinin and an unknown kinin. The activity of the enzyme was increased 10-fold in the presence of thiol groups (dithiothreitol) and inhibited by leupeptin (90%) and to a lesser extent by aprotinin (49%), TLCK (46%) and soybean trypsin inhibitor (27%). Pepstatin and PMSF did not inhibit the enzyme. Studies on substrate specificity, pH optimum and agents which inhibit T-kgnase activity demonstrate that this enzyme is different from plasma and tissue kallikreins, cathepsin D, esterase A and esterase B (other known kininogenases). It is the first thiol-activated kininogenase to be reported.

Role of dipeptidyl peptidase IV in uptake of peptide nitrogen from beta-casomorphin in rabbit renal BBMV.

We examined the handling of radiolabeled beta-casomorphin, Tyr-Pro-[3H]Phe-Pro-Gly, by rabbit renal brush-border membrane vesicles (BBMV). The uptake of radiolabel into the vesicles was Na+-independent, but an inward-directed H+ gradient stimulated the uptake. The H+ gradient-dependent uptake was further accelerated by an interior-negative membrane potential, but inhibited in the presence of a protonophore. Treatment of the membrane vesicles with diisopropylfluorophosphate (DFP) greatly reduced the uptake of the radiolabel. Control as well as DFP-treated vesicles exhibited H+ gradient-dependent Gly-Sar uptake. Unlabeled beta-casomorphin inhibited Gly-Sar uptake in control vesicles, but the inhibition was significantly reduced in DFP-treated vesicles. DFP inhibited the activity of dipeptidyl peptidase IV in these vesicles and there was a direct correlation between the activity of the enzyme and the capacity of beta-casomorphin to inhibit Gly-Sar uptake. Many di- and tripeptides reduced the uptake of Gly-Sar and the uptake of radiolabel from beta-[3H]casomorphin to a similar extent. We conclude that beta-casomorphin is hydrolyzed by dipeptidyl peptidase IV and the products are transported into the vesicles by the H+ gradient-driven peptide transport system. This conclusion is supported by the results from the analysis of the incubation medium by high-performance liquid chromatography that showed rapid hydrolysis of the pentapeptide by brush-border membranes to di- and tripeptides.

Acquired factor VIII deficiency in an elderly woman on tamoxifen.

A case is presented and acquired factor VIII deficiency is discussed. The studied patient was elderly and had cancer of left breast, cancer of the head of the pancreas, history of blood transfusions, and was on tamoxifencitrate therapy for breast cancer. Any one of the above factors could have been responsible for production of factor VIII deficiency.

Increased plasma level of T-kininogen in rats treated with Freund's adjuvant.

Studies have been carried out to clarify which component of plasma kininogen in rats increased in the inflammatory condition induced by an injection of Freund's complete adjuvant. Plasma T-kininogen, which was measured by assaying the amount of T-kinin liberated by trypsin treatment, remarkably increased in parallel with the severity of paw swelling following the intradermal injection of adjuvant into the rat hindpaw. Treatment with indomethacin or dexamethasone following an injection of adjuvant suppressed the increase in T-kininogen level as well as the development of paw swelling in rats. These results indicate that T-kininogen, the newly found precursor of T-kinin, is the main component of plasma kininogen which responds to the inflammatory stimulus in adjuvant arthritis.

Release of T-kinin and bradykinin in carrageenin induced inflammation in the rat.

Plasma and inflammatory fluid kininogen levels, and blood and inflammatory fluid free kinin levels were determined in rats 24 h after the injection of carrageenin into an air pouch. Plasma T-kininogen levels increased 7-fold. In the inflammatory fluid levels reached 8 micrograms/ml. Blood levels of free kinin showed a 5-fold increase. The kinins were identified on HPLC as T-kinin (Ile-Ser-bradykinin) and bradykinin, 63 and 37%, respectively. These results indicate for the first time that free T-kinin as well as bradykinin is released during an inflammatory response in rat and confirms our previous finding that T-kininogen may be a major acute-phase protein in inflammation.