Relationships between Mechanical Nociceptive Threshold and Activity of Antioxidant Enzymes in Male Rats with Experimental Type I Diabetes Mellitus.

We analyzed the dynamics of neuropathic pain development and changes in catalase and superoxide dismutase (SOD) activities in the brain, liver, and skeletal muscles of male Wistar rats with 1-month streptozotocin-induced diabetes mellitus. A decrease in mechanical nociceptive threshold was revealed that progressed during the disease progress. Insulin treatment restored nociceptive threshold in diabetic animals to the control values. Catalase activity in the liver and skeletal muscles of diabetic rats increased by 1.5 and 2 times, respectively, in comparison with the control, while insulin treatment reduced enzyme activity to the control level. In the brain, catalase activity was reduced by 1.5 times and insulin therapy did affect this parameter. SOD activity in the studied tissues remained unchanged during diabetes and was not affected by insulin therapy. A strong negative correlation between nociceptive threshold in rats and catalase activity in their liver and skeletal muscles was found.

[THE CHANGES OF NOCICEPTIVE THRESHOLD AND ACTIVITY OF THE ADENYLYL CYCLASE SYSTEM IN THE SKELETAL MUSCLES OF RATS WITH ACUTE AND MILD TYPE 1 DIABETES MELLITUS ].

Diabetic peripheral neuropathy (DPN) is one of the most common complications of the type 1 diabetes mellitus (DM1). The aim of the work was to study the dynamics of a painful DPN and functional state of the hormone-sensitive ACSS in the skeletal muscles of rats with the models of acute and mild DM1, as well as the study of impact on them of insulin therapy with different ways of hormone delivery - intranasal and peripheral. In both models of DM1, the level of nociceptive threshold in rats decreased and the stimulatory effects of guanine nucleotides (GppNHp) and adrenergic agonists (isoproterenol, BRL-37344) on adenylyl cyclase (AC) activity were attenuated. The AC stimulating effect of relaxin decreased in animals with acute DM1, but in mild DM1, the decrease was insignificant. Peripheral administration of insulin in rats with acute DM1 increased the nociceptive threshold and partially restored the AC effect of ß 3-agonist BRL-37344. Intranasal administration of insulin in rats with DM1 also increased the nociceptive threshold and partially restored the basal and BRL-37344-stimulated AC activity in the skeletal muscles of diabetic animals. Thus, in the skeletal muscles of rats with acute and mild DM1 the nociceptive sensitivity and the functions of ACSS were disturbed, and they were partially restored by the treatment with peripheral (acute DM1) or intranasal (mild DM1) insulin.

[Spatial memory and regulation of brain adenylyl cyclase by serotonin and dopamine in rat with streptozotocin diabetes].

The most common complication of diabetes mellitus of the type 1 (DM1) is a cognitive deficiency, which develops as a result of neurodegenerative changes in the brain. The aim of this work was to study the learning and spatial memory in rats with streptozotocin DM1 with different duration (1.5 and 6 months), as well as the activity of adenylyl cyclase signaling system (ACSS) sensitive to agonists of the serotonin and the dopamine receptors in the brain of diabetic rats. Our experiments demonstrated that rats with 1.5-months DM1 has no changes in spatial memory which were evaluated in a Morris water maze whereas in rats with 6-months DM1 the spatial memory and learning ability were decreased. The alterations of the regulation of adenylyl cyclase by agonists of types 1 and 6 serotonin receptors and type 2 dopamine receptors were found in both the 1.5- and 6-months DM1 which indicates their importance in the development of cognitive deficiency. Abnormalities in the. brain ACSS can be considered as key factors in the etiology and pathogenesis of cognitive dysfunctions in DM1. Hypothesized that cognitive deficiency occurs only in the later stages of DM1 due to alterations in the serotonin and dopamine signaling systems of the brain.

[Behavioral and neurochemical aspects of the antidepressive action of GSB-106 dipeptide BDNF fragment].

The behavioral and neurochemical effects of synthetic dipeptide fragment GSB-106 of BDNF, administered in a single dose of 0.1 mg/kg (i.p.), have been studied in comparison to amitriptyline (10 mg/kg, i.p.) on the Nomura depressive state model employing forced-rotating-wheel swim test (FST) in Wistar rats. Amitriptyline is known to increase both the number of wheel turns and the index of correlation between the number of turns in the first and last 5-min intervals of observation. It is established that GSB-6 produces a pronounced antidepressant effect comparable to that of amitriptyline, while not influencing the content of monoamines in brain structures of intact (non-depressive) rats. HPLC study showed that GSB-106 increased the complex parameters of dopamine metabolism (DOPAC/DA and HVA/DA) in nucleus accumbens and striatum of rats undergoing FST as compared to the same indices in intact animals. A decrease in the norepinephrine (NE) content by 50% was detected in striatum and hippocampus of rats with depression model. GSB-106 to significantly increased the number of wheel turnings and prevent the elevation of DA and its metabolite DOPAC levels in hypothalamus. A decrease in 5-HIAA (serotonin metabolite) content was also detected in frontal cortex and hypothalamus.

Initial stages of the insulin signaling system in the brain of rats with experimental diabetes mellitus.

We studied reactivity of insulin signal pathway elements, insulin receptor and insulin receptor substrate protein-2 (IRS2 protein), in rat brain in response to insulin insufficiency and insulin resistance during the development of experimental type 1 or type 2 diabetes mellitus. In type 1 diabetes mellitus characterized by acute insulin insufficiency, specific binding of insulin in rat brain increased 2-fold in comparison with the control and IRS2-gene expression in rat hypothalamus and cortex 2-4 fold surpassed the normal values. In type 2 diabetes mellitus (110 and 190 days of development), changes in the test parameters in rat brain were less pronounced. These findings attest to involvement of the brain insulin signal pathway into the response to systemic insulin deficiency in type 1 diabetes mellitus.

Pleiotropic action of insulin-like peptides of mollusk, Anodonta cygnea.

Insulin-related peptides (IRPs) from ganglions of mollusk, Anodonta cygnea, were purified and characterized (IRP1-IRP13) using insulin and insulin-like growth factor-I (IGF-I) radioreceptor test systems. The IRPs were able to bind to insulin and IGF-I receptors. Dose-dependent curve slopes indicated that most IRPs bind with higher affinity to IGF-I receptors than to insulin receptors. The IRP regulatory action on the activity of the adenylyl cyclase signal system showed that these peptides stimulated adenylyl cyclase and GTP-binding activity of G-proteins to the same extent as insulin and IGF-I. The data obtained suggest polyfunctional IRP action that apparently is determined by the molecular structure of individual isoforms.

Sensitivity of adenylyl cyclase signaling system of the mollusk Anodonta cygnea ganglions to serotonin and adrenergic agonists.

For the first time, the adenylyl cyclase system (ACS) sensitive to biogenic amines in the mollusk Anodonta cygnea ganglions was revealed and characterized. Serotonin and isoproterenol stimulated AC activity and GTP-binding activity of heterotrimeric G-proteins. The AC-stimulating action of serotonin and isoproterenol was blocked by cyproheptadine and adrenergic antagonists, respectively. Using synthetic C-terminal peptides of G-protein alpha-subunit, it was shown that the biogenic amines realized their action on the ACS through different G-protein types: serotonin and isoproterenol activate G(s)-protein, while adrenaline preferably activates G(i)-protein.

[Purification and ligand-receptor analysis of insulin-related peptides from pedal ganglion of the mollusc Anodonta cygnea]. / Ochistka i ligand-retseptornyi analiz insulinopodobnykh peptidov pedal'nogo gandliia molliuska Anodonta cygnea.

Six insulin-related peptides (IRPs) from pedal ganglions of the molluscs Anodonta cygnea have been isolated and purified by reverse-phase chromatography. Each peptide (designated as IRP8-IRP13) showed its own retention time on the HPLC column. The testing of IRPs in radioreceptor systems specific for insulin and insulin growth factor-I (IGF-I) showed their ability to bind to both types of receptors. The concentration of IRPs, producing a 50% inhibition of porcine 125I-insulin binding with rat liver plasma membrane receptors (IC50) for IRP 10, was 1167 nM, IRP11--833 nM, IRP13--1333 nm. IRP8, IRP9, IRP12 in the maximum concentration of 10(4) ng/ml displaced less than 50% of labeled hormone. All of the six peptides were capable of competing with human 125I-IGF-I for binding to receptors of a fraction of rat brain membranes. IRP8, IRP9 and IRP12 had close means equal to 1167 nM, 1500 nM, 1167 nM, respectively. Another group including IRP10, IRP11 and IRP13 showed a much higher activity (833, 83 and 500 nM, respectively). The results obtained from radioligand analysis revealed the predominance of IGF-I binding properties in all peptides of pedal ganglions. At the same time, apparent proximity of IRP's physico-chemical characteristics to porcine insulin, and also the revealed dose-dependent binding to both insulin and IGF-I receptors suggest a bifunctionality of mollusc peptides. The expression level of this bifunctionality may be associated with the molecular structure pecularities of individual isoforms.

[Goodpasture's syndrome as a cause of pulmonary hemorrhages]. / Sindrom Gudpaschera kak prichina legochnykh gemorragii.

Analyzing the case histories of 5 patients with Goodpasture's syndrome who have admitted to an emergency clinic for suspected tuberculosis leads to the conclusion that the onset of the disease appeared as intoxication and lung damage, and evolving general weakness, fever, cough. Hemopoiesis appeared just when overall clinical manifestations appeared, it varied from single sputum blood filaments to more frequent mows of pure red blood sputum for several weeks, but there was never an increasing hourly progressively and this failed to cause a rapid drop of hemoglobin. Anemia is attributable by pulmonary blood imbibition, intoxication, and suppressed hemopoiesis in renal failure rather than by external blood loss as hemoptysis.

A conserved asparagine makes an essential contact to an RNA adenosine or cytidine.

Abstract Post-transriptional regulation of yeast ribosomal protein L30, RPL30, requires the formation of a complex comprised of RPL30 and its RNA transcript [J. Vilardell and J. R. Warner, Genes & Dev. 8, 211-220 (1994)]. Mutational analysis of both the RNA and the protein reveals that an asparagine-adenosine contact is important. Replacement of the asparagine by alanine weakens binding dramatically, but substitution of the adenosine by cytidine or guanosine slightly increases or decreases respective binding affinities for RPL30. The structure of the complex has been solved by NMR and shows a conserved asparagine in position to form two hydrogen bonds with adenosine's Watson-Crick face [H. Mao, S. A. White and J. R. Williamson, Nat. Struct. Biol. 6, 1139-1147 (1999)]. Asparagine is necessary for this interaction but relatively small differences in binding affinity are measured for three different nucleotides.

[Erroneous laparotomy in emergency surgery]. / Oshibochnye laparotomii v neotlozhnoi khirurgii.

The authors studied the data concerning 101 patients who had undergone erroneous laparotomy for suspected acute surgical disease; these accounted for 0.4% of all the patients who were operated on for emergency indications in the same period. Eleven patients died. The operation was undertaken for an erroneous diagnosis of acute appendicitis (32 patients), acute cholecystitis (18), perforating gastric ulcer (15), peritonitis of unknown etiology (14), acute intestinal obstruction (5), strangulated hernia (3), destructive pancreatitis (3), tumor of the large intestine complicated by obstruction (3), abdominal abscess (2), thrombosis of the mesenteric vessels (1), ovarian apoplexy (1), closed abdominal trauma with injury to the viscera (4 patients). Diseases simulating the clinical picture of "acute abdomen" but not requiring an emergency operation were as follows: female reproductive (20 patients), pancreatic (11), renal diseases (11), hepatitis, cirrhosis of the liver (10), cardiovascular (9), pulmonary diseases (5), mesoadenitis (5), Crohn's disease (3), chronic colitis (3), carcinomatosis of the peritoneum (3), herpes zoster (3), and other diseases and injuries (20 patients). The main causes of the diagnostic and tactical errors were objective difficulties in the differential diagnosis due to similar symptomatology, as well as errors in the examination of the patient and haste in making a decision to make an operation.

[Treatment of peptic ulcer hemorrhages]. / Lechenie iazvennykh gastroduodenal'nykh krovotechenii.

The article analyses experience in treatment of 297 patients with gastroduodenal bleeding of ulcerous etiology. Operative interventions after arrest of bleeding and the appropriate preoperative management produce better results (the mortality rate, 3.3%) than those of emergency operations (the mortality rate, 15.7%). It is therefore advisable to start treatment of patients with gastroduodenal bleeding by means of nonoperative measures which proved effective in 61.6% of cases. In doubtful reliability of hemostasis, patients with moderate and severe bleeding should be operated on in the immediate days after hospitalization without waiting for a possible recurrent bleeding. Gastric resection is the main type of operative intervention in bleeding from a gastric ulcer. In a bleeding duodenal ulcer both resection of the stomach and economical operations--vagotomy, excision or closure of the ulcer, pyloroplasty--are equally competent.

[Radiation treatment of bladder cancer using different fractionation regimens]. / Luchevoe lechenie raka mochevogo puzyria pri razlichnykh rezhimakh fraktsionirovaniia.

The paper is devoted to a follow-up of 177 bladder cancer patients. The problems of providing radiotherapy with the use of hyperfractionation of a radiation dose were discussed. Despite an increase in a tumor dose by 15%, no increase in the number and expression of local radiation reactions is observed. Enhanced therapeutic efficacy was observed, particularly in cases of locally advanced tumors (T3). Three years after conventional radiotherapy 44% of the patients were alive, after hyperfractionated irradiation--69%.