Microwave Radiometry (MWR) temperature measurement is related to symptom severity in patients with Low Back Pain (LBP).

Microwave Radiometry (MWR) has the advantage that measurements of internal (i.e. deep) tissue temperature may be obtained non-invasively by measuring naturally emitted radiation in GHz range. The goal of the present study is to further the development of MWR for clinical application in assessment of patients with Low Back Pain (LBP). In particular, a protocol was developed in which MWR was used to measure internal temperature at the level of the spinous processes of the L1 to L5 vertebral bodies along median and left and right para-vertebral lines. The protocol was used to study 48 patients with clinically confirmed acute or sub-acute LBP and 27 Controls. Analysis revealed there to be a significant increase in deep tissue temperature with increasing pain severity as measured by using a Visual Analogue Scale (VAS) in patients with LBP (p < 0.05). In conclusion, MWR potentially allows for objective assessment of the magnitude of clinical symptoms in patients with LBP and shows promise for measuring pain severity.

GPCR heteromers and their allosteric receptor-receptor interactions.

The concept of intramembrane receptor-receptor interactions and evidence for their existences were introduced in the beginning of the 1980's, suggesting the existence of receptor heterodimerization. The discovery of GPCR heteromers and the receptor mosaic (higher order oligomers, more than two) has been related to the parallel development and application of a variety of resonance energy transfer techniques such as bioluminescence (BRET), fluorescence (FRET) and sequential energy transfer (SRET). The assembly of interacting GPCRs, heterodimers and receptor mosaic leads to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. The receptor interface in the GPCR heteromers is beginning to be characterized and the key role of electrostatic epitope-epitope interactions for the formation of the receptor heteromers will be discussed. Furthermore, a "guide-and-clasp" manner of receptor-receptor interactions has been proposed where the "adhesive guides" may be the triplet homologies. These interactions probably represent a general molecular mechanism for receptor-receptor interactions. It is proposed that changes in GPCR function (moonlighting) may develop through the intracellular loops and C-terminii of the GPCR heteromers as a result of dynamic allosteric interactions between different types of G proteins and other receptor interacting proteins in these domains of the receptors. The evidence for the existence of receptor heteromers opens up a new field for a better understanding of neurophysiology and neuropathology. Furthermore, novel therapeutic approaches could be possible based on the use of heteromers as targets for drug development based on their unique pharmacology.

Possible role of receptor heteromers in multiple sclerosis.

Recent results suggest that cytokine and glutamate receptors can interact directly and form receptor heteromers. Due to such heteromers, cytokines can act not only as classical neuromediators but also directly enhance glutamate gated ion channel activity via allosteric mechanisms. Our opinion is that such heteromers may lead to enhanced glutamate neurotoxicity in pathogenic processes of multiple sclerosis. Thus, agents targeting evolutionary conserved leucine-rich motifs responsible for such dimerization of receptors may represent a useful strategy to inhibit excitotoxicity in multiple sclerosis.

Effect of artrofoon on parameters of endogenous intoxication and activity of myeloperoxidase in leukocytes from patients with postoperative peritonitis.

We studied the possibility of using artrofoon in the treatment of patients with localized suppurative postoperative appendicular peritonitis. A significant inhibiting effect of the preparation on endogenous intoxication parameters was demonstrated. Inhibition of myeloperoxidase hyperactivity is considered as a possible mechanism of the therapeutic effect of artrofoon as a component of complex therapy.

[The condition of the oxidant-antioxidant system of plasma and of blood erythrocytes in patients with severe renal insufficiency, anuria stage, due to compression trauma]. / Sostoianie oksidantno-antioksidantnoi sistemy plazmy i éritrotsitov krovi u bol'nykh v anuricheskoi stadii ostroi pochechnoi nedostatochnosti na fone kompressionnoi travmy.

The lipid peroxidation processes as well as the activity of the antioxidant system of plasma and of blood erythrocytes were analyzed in severe renal insufficiency due to acute compression trauma. The levels of diene conjugates, malonic dialdehyde and shiff bases were found to be reliably higher in plasma in the anuria stage; as for erythrocytes, only the level of the final peroxidation products, i.e. shiff bases, turned out to be higher in their case. The antioxidant system reaction was as follows: a reliable decrease of the ceruplasmin level was registered in blood plasma, and a reduced activity of superoxide dismutase was detected in erythrocytes. No changed catalase activity was registered either in plasma or erythrocytes versus the controls. The occurred lipid-peroxidation activation had, in the erythrocyte membranes, a negative effect on the protein-lipid contact zones. According to the obtained results, it is necessary to use antioxidants and activation of the non-enzyme system within the complex therapy for the purpose of preventing the secondary damage to cellular membranes.

A formal model of an artificial immune system.

The paper presents a mathematical model based on the features of antigen-antibody bindings in the immune system. In the natural immune system, local binding of immune cells and molecules to antigenic peptides is based generally on the behavior of surface proteins. In particular, immune cells contain proteins on their receptors, and apparently, these proteins play the key role both in immune response and recognition processes. In this work, we consider the immune cells in the form of formal B-cell and formal T-cell and develop a mathematical model of their interactions. We refer this model as the formal immune system (FIS). The paper provides an analysis of a network of bindings (or interactions) among the formal proteins of the FIS.

[The mechanisms of action of ketamine]. / Mekhanizmy deistviia ketamina.

The review systematizes the latest data on the main mechanisms of realization of some pharmacological properties of ketamine which are particularly valuable in the treatment of many diseases and conditions. The authors present the main aspects of the ketamine effect on the central mechanisms of anesthesia and hemodynamics and give the characteristics of its neuroprotective action. It is shown that these effects are realized also at the cost of the non-competitive blockade of the NMDA receptors in the central nervous system.

[A neuropharmacological analysis of ketamine analgesia during the central stimulation of alpha 2-adrenoreceptors]. / Neirofarmakologicheskii analiz ketaminovoi anal'gezii pri tsentral'noi stimuliatsii al'fa 2-adrenoretseptorov.

The experiments on albino rats showed that clofeline administered in a subanalgesic dose significantly potentiates the analgesic effect of ketamine at the segmental and suprasegmental levels mainly through mu-opiate and partially through beta 2-adrenergic chains. The initiating role in potentiation belongs to the activation of alpha 2-adrenoreceptors. The analgesic effect of ketamine at the segmental and suprasegmental levels is implemented through alpha 2-adrenergic apparatus and at the suprasegmental level is additionally of naloxone-depended character. The clinical trials showed that a preliminary administration of clofeline during postoperative analgesia with ketamine potentiates and prolongs the analgesic action of the latter.

[Neuropharmacologic analysis and clinical course of ketamine anesthesia during central alpha2-adrenostimulation with clopheline]. / Neirofarmakologicheskii analiz i klinicheskoe techenie anestezii ketaminom pri tsentral'noi al'fa2-adrenostimuliatsii klofelinom.

The experiments on white male rats have established that clopheline preinjection shortens the latent period and prolongs the duration of ketamine anesthesia due to alpha 2-, alpha 2- and beta 2-adrenoceptor mechanisms, respectively. An additional administration of prazosin and naloxone (0.1 mg/kg) potentiates the duration of combined clopheline and ketamine anesthesia. The duration of ketamine anesthesia alone remains unchanged in simultaneous alpha 1- and alpha 2-adrenoceptor blockade with phentolamine, however, it is prolonged in alpha 1-adrenoceptor blockade and shortened in alpha 2-adrenoceptor blockade with prazosin and yohimbine, respectively. Tachycardiac effects of ketamine are removed with clopheline due to alpha 2-adrenostimulation and beta 1-adrenoblockade with talinolol or attenuated upon reserpine administration. The combined use of clopheline and ketamine for the termination of pregnancy, as compared to combined diazepam and ketamine anesthesia, prolongs the duration of anesthesia, normalizes basic hemodynamic parameters prior to and following the injection of an anesthetic and promotes to a more adequate discontinuation of anesthesia.

[Role of tricyclic antidepressants in the central regulation of hyperalgesia and stress analgesia]. / O roli tritsiklicheskikh antidepressantov v tsentral'noi reguliatsii giperalgezii i stress-analgezii.

The effect of hypophysectomy (HE) on pain thresholds was studied in female noninbred rats. Hyperalgesia was observed after HE since the first till the sixth day of the observation period. Droperidol (1 mg/kg i.p.) and amitryptyline (5 mg/kg i.p.) produced hyperalgesia in sham-operated rats, which was potentiated in hypophysectomized animals. In rats taken into the experiment 3 days after operation, no increase in the pain threshold was recordable during the 30-minute painful stress, and poststress autoanalgesia did not develop subsequently. The opposing data were obtained in sham-operated animals. On intraperitoneal administration of phentanyl (25 micrograms/kg) after the 30-minute painful stress hypophysectomized rats did not manifest any potentiation of its analgesic effect in contradistinction to sham-operated animals. Simultaneous administration of phentanyl at the same dose and melipramine (5 mg/kg i.p.) produced considerable potentiation of analgesia if administered after stress. In hypophysectomized rats, that effect was somewhat reduced.

[Neuropharmacology of stress analgesia]. / K neirofarmakologii stress-anal'gezii.

Painful and non-painful stresses have a different line of action on analgetic activity of phentanyl. Hyperalgetic action of immobilization stress is supposed to be linked with impairment of the functioning of the thalamocortical serotonin-sensitive system that gets activated before the development of maximal analgesia in non-stressed cats. Droperidol reduces the antinociceptive action of painful stress. Melipramine and tisercin potentiate stress analgesia.

[Protein metabolic status of acute myocardial infarct patients before and after fentanyl and droperidol arrest of the pain syndrome]. / Sostoianie belkovogo obmena u bol'nykh ostrym infarktom miokarda do i posle kupirovaniia bolevogo sindroma fentanilom i droperidolom.

Protein fractions of the initial serum and acid-soluble proteins of the blood serum were examined in patients with acute myocardial infarction with marked pain syndrome before and after removal of the pain syndrome with fentanl and droperidol. It was noted that the total amount of protein in the initial serum and that of acid-soluble proteins were reduced as compared to the group of normal subjects. Disc electrophoresis demonstrated statistically significant differences in all the electrophoretic protein fractions of the initial blood serum. According to disc electrophoresis of acid-soluble proteins the greatest metabolic changes were experienced by proteins of the prealbumin zone. Three hours after the removal of the pain syndrome, protein metabolism did not return to normal. The intensity of quantitative changes in the disc electrophoretic zones remained at the same level as before the removal.

[Pharmacodynamics of the interaction of neuroleptanalgetics]. / Izuchenie farmakodinamiki vzaimodeistviia neiroleptanal'getikov.

The authors carried out a quantitative assessment of pharmacodynamic effects of droperidol (5 and 25 mg/kg) and phentanyl (0.5 and 1 microgram/kg). The effects of the drugs on sensitivity and pain were studied by the "tail jerking" test. The electrophysiological studies included spectral analysis of the EG of the following central nervous system structures: head of the caudate nucleus, substantia nigra, central gray of the midbrain. The quantitative characteristics of the analgesic effect of phentanyl and hyperalgetic effect of droperidol, as well as the potentiation of the antinociceptive effect of phentanyl combined with droperidol were demonstrated. Studies on the EG recorded the appearance of local extremes on the spectrograms within the range of 7 Hz. The use of the method of least squares for comparing the curves of the relationships between the effects of droperidol and phentanyl and their concentrations in the brain enabled deriving the equations that quantitatively characterize the pharmacodynamic effects of interaction of the drugs in question.