Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

Long-term effect of shock wave therapy on upper limb hypertonia in patients affected by stroke.

BACKGROUND AND PURPOSE: Spasticity is a disabling complication of stroke and different noninvasive treatments are used to reduce muscle hypertonia. Shock waves are defined as a sequence of single sonic pulses largely used in the treatment of diseases involving bone and tendon as well as muscular contractures. The effect and duration of extracorporeal shock wave therapy (ESWT) was investigated on muscle hypertonia of the hand and wrist. METHODS: A total of 20 patients affected by stroke associated with severe hypertonia in upper limbs were evaluated. Placebo stimulation was performed 1 week before active stimulation in each patient. Evaluation was performed using the National Institutes of Health and Ashworth scales and video monitoring with a digital goniometer before and immediately after placebo or active stimulation. Motor nerve conduction velocity from abductor digiti minimi were recorded. Patients were monitored at 1, 4, and 12 weeks after active treatment. RESULTS: After active ESWT, patients showed greater improvement in flexor tone of wrist and fingers compared with placebo stimulation. At the 1- and 4-week follow-up visits, a significant decrease of passive muscle tonicity was noted on muscles in all patients receiving active treatment. At 12 weeks after therapy, 10 of the 20 patients showed persistent reduction in muscle tone. There were no adverse events associated with ESWT. CONCLUSIONS: ESWT reduces hypertonia of the wrist and finger muscles for > or =12 weeks after treatment. The possible mechanisms of action of ESWT are discussed.

Short-time non-enzymatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment.

The evidence that nitric oxide (NO) production is possible by a non-enzymatic pathway has already been shown under restrictive experimental conditions. Here we show that NO can non-enzymatically be formed with short-time kinetics (min), by 'bombing' with shock waves a solution containing 1 mM hydrogen peroxide and 10 mM L-arginine. This procedure is widening its medical application with surprisingly positive effects in tissue regeneration and our finding could be one of the first steps for the understanding of the biochemical responsible for these therapeutical effects.

Association of a new type of gliding, filamentous, purple phototrophic bacterium inside bundles of Microcoleus chthonoplastes in hypersaline cyanobacterial mats.

An unidentified filamentous purple bacterium, probably belonging to a new genus or even a new family, is found in close association with the filamentous, mat-forming cyanobacterium Microcoleus chthonoplastes in a hypersaline pond at Guerrero Negro, Baja California Sur, Mexico, and in Solar Lake, Sinai, Egypt. This organism is a gliding, segmented trichome, 0.8-0.9 micrometer wide. It contains intracytoplasmic stacked lamellae which are perpendicular and obliquely oriented to the cell wall, similar to those described for the purple sulfur bacteria Ectothiorhodospira. These bacteria are found inside the cyanobacterial bundle, enclosed by the cyanobacterial sheath. Detailed transmission electron microscopical analyses carried out in horizontal sections of the upper 1.5 mm of the cyanobacterial mat show this cyanobacterial-purple bacterial association at depths of 300-1200 micrometers, corresponding to the zone below that of maximal oxygenic photosynthesis. Sharp gradients of oxygen and sulfide are established during the day at this microzone in the two cyanobacterial mats studied. The close association, the distribution pattern of this association and preliminary physiological experiments suggest a co-metabolism of sulfur by the two-membered community. This probable new genus of purple bacteria may also grow photoheterotrophically using organic carbon excreted by the cyanobacterium. Since the chemical gradients in the entire photic zone fluctuate widely in a diurnal cycle, both types of metabolism probably take place. During the morning and afternoon, sulfide migrates up to the photic zone allowing photoautotrophic metabolism with sulfide as the electron donor. During the day the photic zone is highly oxygenated and the purple bacteria may either use oxidized species of sulfur such as elemental sulfur and thiosulfate in the photoautotrophic mode or grow photoheterotrophically using organic carbon excreted by M. chthonoplastes. The new type of filamentous purple sulfur bacteria is not available yet in pure culture, and its taxonomical position cannot be fully established. This organism is suggested to be a new type of gliding, filamentous, purple phototroph.

Ultrastructural findings in the brain of fruit flies (Drosophila melanogaster) and mice exposed to high-energy particle radiation.

Effects of high energy, heavy particle (HZE) radiation were studied in the brain of the fruit fly (Drosophila melanogaster) exposed to argon (40Ar) or krypton (84Kr) ions. In the flies exposed to argon the fluence ranged from 6 X 10(4) to 8 X 10(7) particles/cm2. The insects were killed 35 days after exposure. Extensive tissue fragmentation was observed at the higher fluence employed. At fluences ranging from 5 X 10(6) (one hit/two cell bodies) to 9 X 10(4) (one hit/90 cell bodies) particles/cm2, swelling of the neuronal cytoplasm and focally fragmented membranes was observed. Marked increase of glial lamellae around nerve cell processes was seen at fluences ranging from one hit/six to one hit/135 cell bodies. In the flies irradiated with krypton, the fluences employed were 5.8 X 10(3) and 2.2 X 10(6) particles/cm2. Acute and late effects were evaluated. In the flies killed 36 hours after exposure (acute effects) to either fluence, glycogen particles were found in the neuroglial compartment. The granules were no longer present in flies killed 35 days later (late effects). As in the flies exposed to argon, neuronal swelling and membrane disruption were observed 35 days after exposure to both fluences. From these studies it appears that the Drosophila brain is a useful model to investigate radiation damage to mature neurons, neuroglia, and therefore, to the glio-neuronal metabolic unit. In a separate study, the synaptic profiles of the neuropil in layers II-III of the frontal cerebral cortex of anesthesized adult LAFl mice were quantitatively appraised after exposure to argon (40Ar) particles. The absorbed dose ranged from 0.05 to 5 gray (Gy) plateau. It was determined that the sodium pentobarbital anesthesia per se results in a significant decrease in synaptic profile length one day after anesthetization, with return to normal values after 2-28 days. Irradiation with 0.05-5 Gy argon particles significantly inhibited the synaptic shortening effect of anesthesia at one day after exposure.

Synaptic plasticity in the cerebral cortex of mice: effects of radiation and anesthesia.

In the neuropil of layers II and III of the frontal cortex of adult mice, as seen in the electron microscope, sodium pentobarbital anesthesia alone results in a significant decrease in synaptic profile length at 1 day after anesthetization, followed by a return to normal or above normal levels after 2-28 days, while the number of synaptic profiles per unit cross section (profile incidence) is not altered; irradiation with 5-500 rad plateau argon particles significantly inhibits the profile shortening effect of anesthesia at 1 day after exposure, but this inhibition is not dose related; an inverse dose relationship in profile incidence appears at 2 days following irradiation with argon particles; at 1 to 2 hours after 150 or 220 rad x-irradiation, profile incidence is significantly reduced while the length is increased, effects that appear to be dose related and unaffected by adrenalectomy.

Removal of histological sections from glass for electron microscopy: use of Quetol 651 resin and heat.

A method is described for using the epoxy resin Quetol 651 and heat for convenient and rapid separation of conventional histological sections from glass slides for subsequent ultrathin sectioning for retrospective electron microscopy. The same method is useful when Epon-Araldite is substituted for the Quetol 651 resin.