10 kHz spinal cord stimulation improves metrics of spinal sensory processing in a male STZ rat model of diabetes.

To explore why clinical 10 kHz spinal cord stimulation (10 kHz SCS) might improve neurological function in a model of painful diabetic neuropathy (PDN), the short-term behavioral, electrophysiological, and histological effects of 10 kHz SCS were studied using adult male streptozotocin (STZ)-induced diabetic Sprague-Dawley rats. Four testing groups were established: Naïve controls (N = 8), STZ controls (N = 7), STZ+Sham SCS (N = 9), and STZ+10 kHz SCS (N = 11). After intraperitoneal injection (60 mg/kg) of STZ caused the rats to become hyperglycemic, SCS electrodes were implanted in the dorsal epidural space over the L5-L6 spinal segments in the STZ+Sham SCS and STZ+10 kHz SCS groups and were stimulated for 14 days.

Frequency-Dependent Neural Modulation of Dorsal Horn Neurons by Kilohertz Spinal Cord Stimulation in Rats.

Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In this study, using a novel preparation, we investigated the impact of varying kilohertz frequency SCS on dorsal horn neuron activation.

Improvement in Protective Sensation: Clinical Evidence From a Randomized Controlled Trial for Treatment of Painful Diabetic Neuropathy With 10 kHz Spinal Cord Stimulation.

Background: Painful diabetic neuropathy (PDN) can result in the loss of protective sensation, in which people are at twice the likelihood of foot ulceration and three times the risk of lower extremity amputation. Here, we evaluated the long-term effects of high-frequency (10 kHz) paresthesia-independent spinal cord stimulation (SCS) on protective sensation in the feet and the associated risk of foot ulceration for individuals with PDN.

Methods: The SENZA-PDN clinical study was a randomized, controlled trial in which 216 participants with PDN were randomized to receive either conventional medical management (CMM) alone or 10 kHz SCS plus CMM, with optional treatment crossover after 6 months.

Simultaneous 10 kHz and 40 Hz spinal cord stimulation increases dorsal horn inhibitory interneuron activity.

Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Low-intensity, paresthesia-free, 10 kHz SCS has demonstrated statistically- and clinically-superior long-term pain relief compared to conventional SCS. 10 kHz SCS has been proposed to operate via selective activation of inhibitory interneurons in the superficial dorsal horn.

Low-Intensity 10 kHz Spinal Cord Stimulation Reduces Behavioral and Neural Hypersensitivity in a Rat Model of Painful Diabetic Neuropathy.

Background: Low-intensity 10 kHz spinal cord stimulation (SCS) has been shown to provide pain relief in patients with chronic pain resulting from diabetic peripheral neuropathy (DPN). However to date, there have been no studies of 10 kHz SCS in animal models of diabetes. We aimed to establish correlative data of the effects of this therapy on behavioral and electrophysiological measures in a DPN model.

Differential Modulation of Dorsal Horn Neurons by Various Spinal Cord Stimulation Strategies.

New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS.

Low-intensity, Kilohertz Frequency Spinal Cord Stimulation Differently Affects Excitatory and Inhibitory Neurons in the Rodent Superficial Dorsal Horn.

Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Compared to traditional high-intensity, low-frequency (<100 Hz) SCS that is thought to produce paresthesia and pain relief by stimulating large myelinated fibers in the dorsal column (DC), low-intensity, high-frequency (10 kHz) SCS has demonstrated long-term pain relief without generation of paresthesia. To understand this paresthesia-free analgesic mechanism of 10 kHz SCS, we examined whether 10 kHz SCS at intensities below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner.

Reduced Heat Generation During Magnetic Stimulation of Rat Sciatic Nerve Using Current Waveform Truncation.

Current truncating circuit designs used in some controllable pulse width transcranial magnetic stimulation systems can be adapted for use with the peripheral nervous system. Such a scaled-down stimulator produces neuromuscular activation using less stimulus energy than described in previous reports of sciatic nerve stimulation. To evaluate the energy reductions possible with current truncation, we performed six in vivo experiments in rats where the magnetic stimulating coil abutted the sciatic nerve.

Linear methods for reducing EMG contamination in peripheral nerve motor decodes.

Signals recorded from the peripheral nervous system (PNS) with high channel count penetrating microelectrode arrays, such as the Utah Slanted Electrode Array (USEA), often have electromyographic (EMG) signals contaminating the neural signal. This common-mode signal source may prevent single neural units from successfully being detected, thus hindering motor decode algorithms. Reducing this EMG contamination may lead to more accurate motor decode performance.

In Vivo Magnetic Stimulation of Rat Sciatic Nerve With Centimeter- and Millimeter-Scale Solenoid Coils.

Previous reports of magnetic stimulation of the peripheral nervous system (PNS) used various coil geometries, all with outer diameters larger than 35 mm, and stimulation energies in the 50 J range to evoke neural excitation. Recent reports of central nervous system (CNS) activation used sub-mm-scale solenoid coils with mJ energy levels. The goal of this study was to translate the lower energy levels from the CNS to the PNS via using smaller coils placed in closer proximity to the neural tissue.

A μm-Scale Computational Model of Magnetic Neural Stimulation in Multifascicular Peripheral Nerves.

There has been recurring interest in using magnetic neural stimulation for implantable localized stimulation. However, the large stimulation voltages and energies necessary to evoke neuronal activity have tempered this interest. To investigate the potential of magnetic stimulation as a viable methodology and to provide the ability to investigate novel coil designs that can result in lower stimulation threshold voltages and energies, there is a need for a model that accurately predicts the magnetic field-tissue interaction that results in neuronal stimulation.

A μm-resolution heterogeneous tissue model for the magnetic stimulation of multifascicular sciatic nerve.

Efficacy of magnetic stimulation of the central or peripheral nervous system depends on the spatial and temporal distribution of the induced electric field generated by the magnetic coil. Therefore, accurate estimation of the induced electric field is crucial to the design and optimization of magnetic coils, particularly as the coil dimensions are reduced. In this work, we developed a numerical model of a multifascicular sciatic nerve to study the effect of tissue heterogeneity on the induced electric field.

Magnetic stimulation of mammalian peripheral nerves in vivo: an alternative to functional electrical stimulation.

Functional electrical stimulation is the current gold standard for stimulating neuronal interfaces for functional neuromuscular and cortical applications, but it is not without its drawbacks. One such fault is the need to have direct electrical contact with the nerve tissue, and any side effects this causes. Functional magnetic stimulation, which works though electromagnetic induction, does not require electrical contact and may be a viable alternative to functional electrical stimulation.

[Changes in the kinetic characteristics of reactions catalyzed by erythrocyte delta-aminolevulinate dehydratase in experimental lead poisoning in rats].

An increase in values of both kinetic parameters (Km and Vmax) of the delta-aminolevulinate dehydratase reaction was observed in blood of rats poisoned with lead. The Km value of the reaction was increased, while Vmax--decreased, after addition of Pb2+ into rat blood in vitro. The results obtained as well as the data published in literature suggest that a compensatory mechanism appears to function in vivo, where a substrate, delta-aminolevulenic acid, plays a triggering role.

[Various regulatory properties of fructose-1,6-diphosphatase of the rat liver under normal conditions and in experimental autoimmune cardiomyopathy].

An increase in fructose-1,6-biphosphatase activity in liver tissue of rats with experimental autoimmune cardiomyopathy was observed. At certain concentrations of EDTA and Mg2+ the AMP-inhibition curves exhibited an intermediate plateau, which appear under different experimental, normal and pathological conditions. The occurrence of complex kinetic curves could be attributed to simultaneous existence of several enzymatic forms differing in the "structural" sites with tightly bound metals, which defines the differences in the kinetic cooperativity and sensitivity to AMP inhibition.

[Desensitization with acetylsalicylate and salicylate of fructose-1,6-diphosphatase from the rabbit liver and skeletal muscles to allosteric inhibition of AMP].

Acetylsalicylate and salicylate partially desensitized fructose 1,6-biphosphatase from rabbit liver and skeletal muscle to allosteric AMP inhibition. The desensitization was accompanied by a decrease in cooperativity between allosteric sites especially distinct for the liver isoenzyme. The effect of salicylate on both isoenzymes was more pronounced than that of acetylsalicylate.

[Complex type of kinetics of fructose-1,6-diphosphate from the rat and rabbit liver].

Studies on rat and rabbit liver fructose 1.6-bisphosphatase inhibition by AMP showed that with an increase in EDTA concentration the hyperbolic AMP inhibition curve is transformed into a sigmoidal one. At intermediate EDTA concentrations, the kinetic curves have a plateau.

[Kinetic and allosteric properties of highly-purified, biosynthetic L-threonine dehydrogenase from brewer's yeast Saccharomyces carlsbergensis].

Kinetic and allosteric propeties of highly purified "biosynthetic" L-threonine dehydratase from brewer's yeast S. carlbergensis were studied at three pH values, using L-threonine and L-serine as substrates. It was shown that the plot of the initial reaction rate (v) versus initial substrate concentrations ([S]0 pH 6.

Purification of commercial preparations of NADP+ from AMP contamination.

A method for purification of commercial preparations of NADP+ from AMP contamination is described. The purification procedure includes one-step anion-exchange chromatography on Dowex-1 (formate) and results in a highly purified salt-free coenzyme with a yield of 70-80%. The chromatography conditions have been selected allowing for complete separation of AMP from NADP+ in a HCOOH concentration gradient.

[Purification of commercial preparations of NADP from AMP].

A method in described for elimination of AMP from commercially available preparations of NADP. The method enables to obtain desalted NADP preparations of 98-99.5% purity with a yield of 70-80% using only one chromatographic step.

[Regulatory enzymopathies].

Hereditary regulatory enzymopathies are considered, molecular-genetic mechanism of which involved a mutation of a structural gene in the locus, coding the much less than regular much greater than amino acid sequence in the allosteric site of regulatory enzyme or the site of the enzyme polypeptide chain, which is responsible for allosteric conformational transition. Dissimilar manifestations of regulatory and classical enzymopathies are discussed. Estimation of kinetic patterns might be very useful in diagnosis of regulatory enzymopathies as shown during study of some molecular pathologies, which occurred, for example, due to molecular pathology of phosphofructokinase and phosphoribosyl pyrophosphate synthetase.

[Certain properties of "biosynthetic" L-threonine dehydratase from subcellular structures of brewers' yeast Saccharomyces carlsbergensis].

The paper is concerned with kinetic properties of the "biosynthetic" L-threonine dehydratase (EC 4.2.1.

[Comparative properties of multiple forms of rabbit muscle phosphofructokinase].

Some properties of three interconvertible forms of rabbit muscle phosphofructokinase specifically eluted from DEAE-cellulose with 19 mM citrate in 0.1 M tris-phosphate buffer, pH 8,0 (I), with 0,3 M buffer (II) and 1.5 M NaCl (III) are compared.