Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin.

Formation of the deposits of protein aggregates-amyloid fibrils in an intracellular and intercellular space-is common to a large group of amyloid-associated disorders. Among the approaches to develop of therapy of such disorders is the use of agents preventing protein fibrillization. Polyaromatic complexes-porphyrins and phthalocyanines-are known as compounds possessing anti-fibrillogenic activity. Here, we explore the impact of related macrocyclic complexes-phthalocyanines (Pc) and octaphenyl porphyrazines (Pz) of Mg and Zn-on aggregation of amyloidogenic protein insulin. Pz complexes are firstly reported as compounds able to affect protein fibrillization. The effect of Pc and Pz complexes on the kinetics and intensity of insulin aggregation was studied by the fluorescent assay using amyloid sensitive cyanine dye. This has shown the impact of metal ion on the anti-fibrillogenic properties of macrocyclic complexes-the effect on the fibrillization kinetics of Mg-containing compounds is much more pronounced comparing to that of Zn analogues. Scanning electron microscopy experiments have demonstrated that filamentous fibrils are the main product of aggregation both for free insulin and in the presence of macrocyclic complexes. However, those fibrils are distinct by their length and proneness to lateral aggregation. The Pc complexes cause the increase in variation of fibrils length 0.9 to 2.7 nm in opposite to 1.4 to 2.0 nm for free insulin, whereas Pz complexes cause certain shortening of the fibrils to 0.8 to 1.6 nm. The averaged size of the fibrils population was estimated by dynamic light scattering; it correlates with the size of single fibrils detected by scanning electron microscopy.

New photosensitive nanometric graphite oxide composites as antimicrobial material with prolonged action.

A new conjugate material based on partially reduced graphite oxide (rGO), silver nanoparticles (Ag), and bis(lysinato)zirconium(IV) phthalocyanine complex (ZrPc) was obtained. Its optical properties (absorption and photoluminescence) after dispersion in solvents were examined. The antimicrobial properties were tested to determine the effect of the composite on the following bacterial strains: Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, which are responsible for many infections and are one of the pathogens the most difficult to treatment. The results obtained for rGO-ZrPc-Ag composite were compared with the properties of GO, GO-ZrPc, and rGO-Ag structures. The influence of the near-infrared irradiation on the antimicrobial activity of ZrPc- and Ag-doped materials against bacteria was observed for very low concentration (0.32mg/mL) of GO-ZrPc to stop the growth of P. aeruginosa in comparison to the nonirradiated sample (41mg/mL). The usefulness of this material in therapy, such as wound infection treatment or endodontic treatment, as antibacterial agent with sustained action was discussed.

Anti-fibrillogenic properties of phthalocyanines: effect of the out-of-plane ligands.

The axially-coordinated phthalocyanines were previously reported as agents possessing strong anti-fibrillogenic properties. In the presented study we used the atomic force microscopy to investigate the intermediates and the products of insulin aggregation reaction formed in the presence of Zr and Hf phthalocyanine complexes that contain out-of-plane ligands of different size and nature. It is shown that while phthalocyanine-free insulin generated mostly amyloid fibrils with a diameter of 2-8nm and a length of up to 5µm, the presence of phthalocyanines with spatial bulky ligands (PcZrDbm2) leads to the redirection of the fibrillization reaction to the formation of the spherical oligomer aggregates with a diameter of 4-12nm. At the same time the phthalocyanine complex PcHfCl2 having the small-volume ligands induces the formation of large size insulin aggregates with a height of about 100nm that are supposed to be amorphous species. The study of the aggregation intermediates showed the certain similarity of the reaction passing for phthalocyanine-free insulin and insulin in the presence of PcZrDbm2. The large-size amorphous species were observed at the beginning of reaction, later they dissociated, leading to the formation and growth of the smaller size particles. The amyloid-sensitive cyanine dye 7519 demonstrates the strong fluorescent response both in the presence of fibrils and spherical oligomers, while it is non-sensitive to amorphous aggregates.

[Optimization of anesthesia during surgery for bullous lung emphysema].

The paper considers a complex of methods for estimating the adequacy of anesthesia, which involves the simultaneous analysis of both the parameters of central hemodynamics, oxygen transport, blood gases, and acid-base balance and those of cardiac rhythm variability. Based on the findings, the authors propose recommendations for optimizing the routine procedure of basis-anesthesia utilizing propofol and basis-anesthesia using ftorotan at surgery for bullous emphysema.

[Choice of optimal respiratory support in acute parenchymatous respiratory failure].

The principal goals of respiratory therapy for acute respiratory failure are to correct gas exchange and to lower respiratory performance. In acute lung lesion syndrome (ALLS) and acute respiratory distress syndrome (ARDS), the oxygenation index (PaO2/FiO2) reflects the degree of alveolar-capillary membrane damage. The changes in PaO2/FiO2 between 400 to 300 at adequate ventilation can be interpreted as occult alveolar-capillary insufficiency. The principle of power saving in ALLS/ARDS is to choose a respiratory support regimen that may ensure oxygenation safety by eliminating the excess work of respiration. The ratio of PaO2/FiO2/VO2 is proposed to consider to be a criterion for the effectiveness of respiratory support in ALLS/ARDS and a marker of energy deficiency. It has been established that the function of the alveolar-capillary membrane is not impaired with the PaO2/FiO2 ratio of more than 1.5 and the ratio of less than 1.0 is typical of the severe course of the severe course of ARDS and suggests both alveolar-capillary membrane damage and energy deficiency.

[Hemocoagulation disorder and its impact on cerebral hemodynamics in patients with type I diabetes mellitus]. / Narushenie gemokoaguliatsii i ee vliianie na tserebral'nyiu gemodinamiky u bol'nykh sakharnym diabetom I tipa.

Indices were studied for the blood coagulation system in 132 patients with insulin-dependent diabetes mellitus (IDDM). The above indices tended to change toward hypercoagulation. The degree of changes was found to be related to duration and severity of illness. Patients presenting with a grave form DM more than 10 years in duration demobnstrated changes in their coagulograms suggesting the development of the chronic disseminated intravascular coagulation syndrome. Correlation has been established between fibrinogen and indices of reoencephalogram reflecting the state of the cerebral vascular system. The conclusion reached was to the effect that hyperfibrinogenemia makes for reduction in the brain pulse blood, is related to the development of venous discirculation, increase in the rigidity of cerebral vessels and heterogenuity of the blood filling in the brain.

[Disordered cerebral hemodynamics in diabetic patients (based on myelographic data)]. / Narushenie tserebral'noi gemodinamiki u bol'nykh sakharnym diabetom (po dannym mielografii).

Overall seventy-six patients with diabetes mellitus (DM) who ranged from 16 to 65 years old were examined. Of these, 62 subjects were given a diagnosis of insulin-dependent DM, 14 insulin-nondependent DM. Moderate severity course of the illness was documented in 32, severe--in 44 patients. All patients revealed a change in the condition of the cerebrovascular system. This was manifested by predominance of hypertonic type rheograms, increased vasomotor tone with vessels of all calibres, changes in the level of pulse blood filling, signs of varying degree venous hypertension. DM duration, severity, level of compensation were all related to the degree of cerebrovascular disturbances.

[A lipid metabolic disorder in diabetics]. / Narushenie lipidnogo obmena u bol'nykh sakharnym diabetom.

A total of 52 patients with diabetes mellitus (DM) who ranged from 15 to 60 years old were examined. Of these, 44 had type I DM, eight patients were afflicted with type 2 DM. 77 percent of the examinees were found out to develop hyperlipoproteinemia (HLP), with type 2b HLP having been diagnosed in 80 percent of the patients, type 4 HLP in 20 percent. The latter abnormality was seen in that group of patients presenting with a severe course of diabetes. In patients with type 1 DM HLP was not age-associated; it was developing in the presence of non-compensated carbohydrate metabolism, with duration of diabetes aggravating the severity of HLP. Type 2 DM patients revealed type 2b HLP with metabolic compensation being unsatisfactory. The above study suggests that lipid metabolism may be caused to return to normal by correction of carbohydrate metabolism, and leads to the belief that treatment of HLP is a worth-while exercise.

[The characteristics of the neurophysiological diagnosis and the main directions in the differentiated therapy of brain edema and swelling in patients who are in a critical state]. / Deiaki osoblyvosti neirofiziolohichnoï diahnostyky i osnovni napriamy dyferentsiiovanoï terapiï nabriaku i nabukhannia holovnoho mozku u khvorykh, kotri perebuvaiiut' u krytychnomu stani.

A total of 186 patients with encephalopathies caused by critical states and reanimation were examined. A complex of neurophysiologic studies was proposed involving impedancemetry of the brain, rheoencephalography, echoencephalography, electroencephalography, ophthalmoscopy. The studies made showed that adoption of the proposed complex permits differentiating the processes of edema, swelling, edema-swelling of the brain as well as determining the condition of cerebral bloodflow and assessing the extent of impairement of cerebral homeostasis. Early diagnosis of edema/swelling of the brain enabled the main trends in the differential therapy of the above processes to be outlined and adequacy of its treatments administration to be effectively controlled on an as-needed basis. Differential approach to diagnosis and treatment of edema and swelling of the brain permitted the parameters studied to return to normal in 75.2 percent of the patients.

[Factors affecting the permeability of cellular and vascular membranes and changes in the enzyme spectrum of the blood in patients having undergone critical states and resuscitation]. / Issledovanie faktorov, vliiaiushchikh na pronitsaemost' kletochnykh i sosudistykh membran, izmenenie fermentnogo spektra krovi u bol'nykh, perenesshikh kriticheskie sostoianiia i reanimatsiiu.

126 patients recovered after critical conditions and resuscitation have been examined. Activation of lipid peroxidation and an increase in biogenic amine level, leading to marked hyperenzymemia, have been established. The activity of blood enzyme markers reflecting the severity of brain damage has been studied. It has been established that the more severe encephalopathy, the higher the activity of blood creatine phosphokinase. 2,3-cyclonucleotide-3-phosphohydrolase (CNPH), reflecting the damage of myelin membrane of nervous fibers, has been studied. The appearance of myelin-CNPH marker in the blood confirms demyelinization of the central nervous system (CNS). The more severe encephalopathy, the more marked the process of CNS demyelinization, the higher the activity of CNPH in the blood serum. The highest CNPH activity is observed in patients with eclampsia and in dead patients with postsystolic syndrome.

[The correction of functional disorders of the cardiovascular system in patients with acute kidney failure treated by hemodialysis]. / Korrektsiia funktsional'nykh narushenii serdechno-sosudistoi sistemy u bol'nykh s ostroi pochechnoi nedostatochnost'iu, lechennykh gemodializom.

A study is presented of the central hemodynamics in 38 patients with severe forms of acute renal failure of different genesis. Disorders were revealed related both to renal failure and use of active methods of extracorporal detoxication, namely, hemodialysis and hemosorption. Measures on the correction of disorders of the central hemodynamics are described.

[Diagnosis and differential therapy of edema and swelling of the brain in patients in critical conditions]. / Diagnostika i differentsirovannaia terapiia oteka i nabukhaniia golovnogo mozga u bol'nykh nakhodiashchikhsia v kriticheskikh sostoianiiakh.

A total of 181 patients found in critical conditions were examined and treated. The use of a complex of neurophysiological studies including brain plethysmography++, rheoencephalography and echoencephalography in patients with encephalopathies made it possible to carry out early and differential diagnosis of brain edema and swelling and to exercise dynamic control over those processes. The basis of the treatment of patients with brain swelling was formed by the drugs that ameliorate microcirculation, cerebral blood flow and brain metabolism. In the treatment of brain edema, use was made of the drugs that normalize blood-brain barrier function and of dehydration therapy.

[Detoxication in the critical state due to rhabdomyolysis]. / Detoksikatsiia pri kriticheskom sostoianii, obuslovlennom rabdomiolizom.

An examination of 92 patients with the crush syndrome and the position compression syndrome was made. All the patients were examined by clinico-biochemical methods, the cardiovascular system being also studied. The leading place is occupied by endogenous intoxication. The metabolic disorders were of a total character involving different links of metabolism. It required inclusion of efferent methods in the program of treatment. The most effective program of using efferent methods of treatment was developed on the basis of the state of hemodynamics and clinico-biochemical peculiarities.

[The complex diagnosis of brain edema--swelling in patients in critical states]. / Kompleksnaia diagnostika oteka--nabukhaniia golovnogo mozga u bol'nykh, nakhodiashchikhsia v kriticheskikh sostoianiiakh.

In an intensive care unit, 181 patients were electrophysiologically investigated (impedance measuring, rheoencephalography, echoencephalography) and ophthalmoscopied, their plasma and red blood cells electrolytes, red blood cells ATP, levels of histamine, serotonin, and monoamine oxidase activity measured and the state of the lipid peroxidation system determined. The combined investigation ensured the early detection of brain edema or swelling and assessment of preponderance of either process. Increase in serotonin, histamine levels and activation of lipid peroxidation system were shown to play an important role in the pathogenesis of these disorders.