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Biomedical subjects

M J Politis

Publications and source records attributed to M J Politis.

At least 19 recordsLinked to original sources

Promotion of second intention wound healing by emu oil lotion: comparative results with furasin, polysporin, and cortisone.

Previous studies showed that twice-daily application of emu oil lotion (mixture of emu oil/fat, vitamin E, and botanical oil) immediately after creation of full-thickness skin defects delayed wound healing 6 days later, perhaps owing to its antiinflammatory actions. If administration was delayed for 48 hours, a two-fold promotion of wound contraction, epithelialization, and infiltration of organized granulation tissue was observed. In the present study, emu oil lotion was applied to full-thickness skin defects in rodents 24 hours after surgery. Six days postoperatively, wound contraction and infiltration of fronts of epithelialized and granulation tissue were assessed. Results indicated a two-fold promotion of all of the above parameters with emu oil lotion. No such effects were exerted by pure emu oil, furasin, cortaid, or polysporin. Data obtained indicate promise for emu oil lotion as an aid in treating full-thickness skin defects if applied after the major postinflammatory stages of wound healing have transpired.

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Beneficial effects of acupuncture treatment following experimental spinal cord injury: a behavioral, morphological, and biochemical study.

The uses and limitations of "first aid" acupuncture treatment were assessed after spinal cord injury in rats. Spinal cords were exposed to a standardized contusion lesion at T8, followed by electroacupuncture stimulation of three points: (a) B1.60 (within the depression dorsal to the lateral malleolus), (b) B1.54 (popliteal space) and (c) Gv.3 (intervertebral space between L4 and L5). Acupuncture treatment was performed at by either 15 min or 24 hrs after surgery. Control rats received spinal cord injury without acupuncture treatment. Animals were assessed at 3 days post-operatively. Results showed improved function (as assessed by a combined behavioral score) in rats which had been treated with acupuncture 15 min after injury relative to those that received no acupuncture treatment. This was accompanied by minimization of post-traumatic cord shrinkage in acupuncture-treated animals and a marked (3 fold) sparing of ventral horn neurons. Plasma cortisol levels rose over 3-fold within 2 hours post-operatively in non-acupuncture-treated rats, where these levels rose less than two fold in acupuncture treated animals. None of the above beneficial effects occurred in rats given acupuncture treatment 24 hrs after spinal cord injury. Results point to a usefulness of acupuncture as adjunct treatment during early stages after spinal cord injury.

Acupuncture Points↗

6-Aminonicotinamide selectively causes necrosis in reactive astroglia cells in vivo. Preliminary morphological observations.

6-Aminonicotinamide (6-AN) is a potent antimetabolite of nicotinamide. Previous studies show a selective gliotoxic effect of 6-AN in nontraumatized nervous system. The present study was undertaken to determine if 6-AN can be selectively toxic against reactive (vs. nonreactive) glial cells distal to site of crush in rat optic nerve. Previously conducted studies indicate that glial cells in crushed optic nerves undergo marked biochemical changes during the second post-operative week. In the present study, 6-AN was administered by i.p. injection 5 days after right optic nerve crush in doses of either 5 or 10 mg/kg body weight. Rats were killed 2 days after injection. High doses of 6-AN resulted in loss of astrocytes and intracellular glial edema in both crushed and unoperated optic nerve. Results were more dramatic in traumatized nerve. Low doses caused degenerative glial changes in reactive, but not in unoperated optic nerve. Injection of 5 mg doses of 6-AN at 13 days post-operatively caused degeneration of reactive astrocytes. The possibility of using 6-AN to selectively kill highly metabolic reactive astrocytes after CNS injury is discussed.

6-Aminonicotinamide↗

The short-term effects of delayed application of electric fields in the damaged rodent spinal cord.

Previous studies have indicated that the application of electrical fields to the contused rat spinal cord could result in a partial return of function within 3 weeks after injury/treatment. Whether similar functional recovery could be established after a delay in the treatment was investigated. Rat spinal cords were contused and allowed to recover untreated for 10 days. At that time, a stimulator delivering 3 microA of direct current was applied to the dorsal portion of the cord such that the cathode was oriented either rostral or caudal to the lesion. Inactive stimulators were also used as controls. Rats were then assessed behaviorally and clinically at weekly intervals up to 3 weeks on an inclined plane and then killed for histological assessments. The results indicate that both the "cathode rostral" and "anode rostral" groups performed statistically significantly better on the inclined plane than the "no current" group. The cathode rostral and anode rostral group animals also demonstrated superior motor abilities. The number of axons in the dorsal funiculi rostral to the lesion in the actively treated groups were also statistically significantly greater than no current controls. The cathode rostral group animals demonstrated a greater number of viable neuronal cell bodies near the site of the lesion. These data suggest that electric fields may facilitate functional recovery and regeneration in the mammalian spinal cord, even after a delay in such treatment.

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Exogenous laminin induces regenerative changes in traumatized sciatic and optic nerve.

Laminin is an extracellular matrix component which can promote neuritic elongation in vitro and has been implicated in the promotion of nerve regeneration in vivo. The present study was undertaken to determine if implantation of Elvax pellets containing exogenous laminin distal to site of lesion could promote regenerative responses in vivo in the adult rat peripheral (sciatic) and central (optic) nerve. In peripheral nerve preparations, Elvax pellets containing laminin or collagen were assessed for their ability to "lure" transected axons into 5-mm-long silicone tubes. In optic nerve studies, laminin pellets were inserted distal to site of nerve crush, and the extent of axonal elongation 2.5 mm to the injury site was assessed. Laminin-containing pellets appeared to support appreciable axonal elongation in both systems. This effect was dose-dependent and not exerted by collagen pellets, substrate-free pellets, or pellets containing irradiated laminin. Collagen IV had some beneficial effect in peripheral, but not central, nerve preparations.

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Enhanced survival of full-thickness skin grafts following the application of DC electrical fields.

The present study was undertaken to determine if uses of exogenous electrical fields could improve the posttraumatic quality of dermis and epidermis in isolated grafts in the rat. In blinded procedures, a full-thickness area of skin was removed and reattached to the original site. A galvanic device delivering 4.5 microA of direct current was applied using three electrode orientations: (1) anode above graft (AT; N = 8), (2) cathode above graft (CT; N = 7), and (3) no current (NC; N = 7). Current delivery was discontinued 4 days postoperatively. Quantitative assessment at 7 days postoperatively indicated the presence of necrotic skin over 80 to 90 percent of the graft surface area in NC and CT animals. In contrast, only 50 percent of the graft area was necrotic in AT rats. Histologic examinations indicated a significantly thickened dermis in the AT (versus NC and CT) rats, accompanied by patches of multilayered intact epidermis, which was virtually absent from the other experimental groups. Results are consistent with the hypothesis that direct-current stimulation can affect skin graft survival and repair.

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Treatment of the damaged rat hippocampus with a locally applied electric field.

Previous studies have indicated that axons may be directed to regenerate toward the cathodal source of a locally applied D.C. electric field. In the present studies, similar galvanotropic effects were tested after partial denervation of the rat hippocampus. Following unilateral fimbrial lesions, 1.5 microA of direct current was applied locally to the tissue for 4 weeks. In the experimental group, the distal (temporal) portion of the hippocampus was located near the cathodal electrode, while the proximal (nasal) portion was located near the anode. In two control groups, either the current was reversed, or there was not current delivered to the tissue. Spontaneous alternation behavior 4 weeks post-operatively in the "cathode distal" rats provided results comparable to those in unoperated (normal) animals, whereas the control animals exhibited statistically significantly greater deficits in memory. The ability to learn the location of a submerged platform in a water tank was evident in unoperated and "cathode distal" animals, but not in either of the control groups. Hippocampal acetylcholinesterase activity in "cathode distal" animals was lower than in unoperated animals, but statistically significantly greater than in the other control animals. Results are consistent with the contention that locally applied weak direct current can modulate long term sequellae of hippocampal injury.

Acetylcholinesterase↗

Exogenous interleukin regulates growth of C6 tumors in vivo.

Elvax pellets containing interleukin 1 (IL-1) or 2 (IL-2) were assessed for their ability to alter the growth of transplanted C6 cells in rat. C6 cells were injected into the left caudate of Sprague Dawley rats. At the time of tumor cell injection, or 9 days later, Elvax pellets containing either 50 or 200 units of interleukin were inserted into the dorsal aspect of the caudate. Animals were killed 16 days later and the volume of tumors determined. Results showed that introduction of low-dose IL-2 pellets at time of C6 cell injection virtually prevented establishment of tumors, whereas low-dose IL-1 pellet insertion resulted in nearly a threefold increase in tumor size relative to control preparations. Insertion of high-dose IL-2 pellets 9 days after C6 cell injection decreased tumor growth relative to controls by nearly twofold, low-dose pellets having no effect. These effects appear to be mediated by alterations in host brains, vs interleukin-moderating effects on growth of C6 cells themselves, since (a) no effect of IL-2 on C6 cell growth in vitro could be demonstrated and IL-1 appeared to enhance their proliferation in culture, and (b) IL-1 pellets diminished and IL-2 pellets enhanced infiltration of inflammatory cells into brain when implanted into brain after a "stab" wound.

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Inhibition of reactive gliosis in vivo by exogenous axolemma and myelin fractions.

Exogenous myelin- or axolemma-enriched fractions were assessed for the ability to inhibit biochemical and morphological expressions of reactive gliosis in rat optic nerve. Elvax pellets containing exogenous myelin, axolemma, whole-brain homogenate, liver, or red cell extracts or no homogenate were inserted into a dural slit in distal regions of crushed optic nerve. Biochemical and morphological expressions of reactive gliosis were assessed at 7 or 14 days postoperatively. Post-traumatic elevations in lactic dehydrogenase activity normally seen at 7 days postoperatively were prevented by placement of Elvax pellets containing myelin or axolemmal fractions into the optic nerve. Morphological analyses indicated an inhibition of post-traumatic elevations in glial cell numbers, surface area, and nuclear size at the 14-day time point. Exposure of the axolemmal fraction to heat or trypsin inactivated its ability to modulate reactive gliotic changes. Myelin fractions were trypsin-sensitive, but not heat-sensitive. In contrast, Elvax pellets containing whole-brain tissue homogenates or liver and red cell membranes had no significant effects on post-traumatic glial changes relative to preparations in which homogenate-free pellets were used.

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Experimental inhibition of reactive gliotic-like changes in astrocytic cultures.

Dibutylcyclic AMP (DiBucAMP) can induce astroblast-containing cultures to form cells which resemble reactive astrocytes observed in vivo. In the present study, myelin- or axolemmal-enriched fractions were assessed for the ability to inhibit (DiBucAMP)-stimulated reactive-like changes in astrocytic cultures. Addition of exogenous myelin- or axolemmal-enriched fractions to DiBcAMP-exposed cultures prevented drug-induced elevation of lactic dehydrogenase (LDH) 2 days after initial addition of the drug and moderated DiBucAMP-induced decreases in the enzyme's activity normally observed 5 days later. The proportion of reactive colonies (i.e., those in which more than 50% of cells are stellate-shape) was significantly lower in cultures exposed to the drug plus myelin or axolemma vs those exposed to DiBucAMP alone. The inhibitory factors in axolemmal fractions were heat sensitive (at 100 degrees C), whereas those in myelin were not. Both fractions were inactivated by trypsin. Whole brain homogenates had no effect on diBucAMP-stimulated changes in culture.

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Facilitated regeneration in the rat peripheral nervous system using applied electric fields.

The efficacy of applied electric fields in promoting regeneration of the transected and frozen rat sciatic nerve was studied. Three groups were studied at 6, 12, and 18 days post-lesion; nerves treated with 1.5 microA of direct current where the cathode was oriented distal to the lesion, nerves treated with the anode distal to the lesion, or no current delivered to the nerve. Regeneration in this severely damaged mammalian peripheral nerve model was quantitated by counting fluorescent antibody profiles to neurofilament protein distal to the lesion site. The results indicated that only cathodal current, applied distal to the lesion, significantly increased the rate of regeneration compared to controls. Such results help to elucidate mechanisms by which electric fields can facilitate regeneration in the mammalian nervous system.

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Mammalian optic nerve regeneration following the application of electric fields.

Previous studies have shown that the application of electric fields to the damaged mammalian nervous system is efficacious in promoting regeneration of peripheral nervous system axons. The present experiments were undertaken to determine whether exogenously applied electric fields can induce regenerative responses in the damaged mammalian central nervous system (CNS). In these studies, chronically delivered direct current was applied to the optic nerve, orienting the cathode distal to the lesion site. Histologic analyses at 3 weeks revealed that the damaged optic nerve did exhibit a regenerative response following treatment. We believe that this represents the first report of regenerative effects on the mammalian visual system using chronic DC electric fields, and we suggest that such galvanic treatment may be used alone or as an adjunct to promoting regeneration of the injured mammalian central nervous system.

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Use of exogenous electric current in the treatment of delayed lesions in peripheral nerves.

A commonly observed clinical problem following nerve injury is the incomplete recovery of function associated with the formation of a neuroma in continuity. In the present study, exogenous direct electric current was tested for its ability to promote growth of axons through a neuroma-like lesion. Neuroma-like structures were created by crushing rat sciatic nerves at two sites 4 mm apart and applying phenol to the intermediate region. A bulbous axonally impenetrable structure is formed 3 weeks later. At that time, silicone cuffs were sewn onto the nerve proximal to the phenol application site and 7 mm distally. In experimental groups, cuffs were attached to wires leading to a subcutaneously implanted Traxon power source, the distal cuff being cathodal. In control groups, cuffs were not electrically connected. In electrically active groups, substantial numbers of myelinated axons were seen distal to the cathode 3 weeks after implantation. Four times fewer fibers were observed in control groups. Footprint patterns from electrically active animals revealed a significant improvement over control neuroma preparations, as quantitated using the Sciatic Functional Index.

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Short term efficacy of applied electric fields in the repair of the damaged rodent spinal cord: behavioral and morphological results.

The short term effects of electric fields applied exogenously to the contused rat spinal cord were studied in a blind experiment. A DC field using 3 microA was applied to the dorsal cord when the lesion was made, and rats were behaviorally tested weekly for up to 3 weeks on an inclined plane. The results show that the "cathode rostral" orientation group of animals performed statistically significantly better on the inclined plane than either the "anode rostral" or the "no current" group. Counts of axons in the dorsal funiculi rostral to the lesion in the "cathode rostral" group were statistically significantly greater than in other groups. The greater number of axons rostral to the lesion site coupled with the superior behavioral performance of the "cathode rostral" group suggest that this treatment may provide an environment suitable for axonal growth and can facilitate functional recovery in the damaged mammalian spinal cord.

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Retina-derived growth-promoting extract supports axonal regeneration in vivo.

The ability of a growth-promoting extract derived from bovine retina was assessed for its ability to support nerve fiber regeneration from proximal stumps of transected sciatic nerves. Proximal stumps of transected rat peripheral nerves were inserted into the single inlet end of a 6 mm long Y-shaped Silastic implant. One of the paired outlets was attached to an Elvax pellet containing the retina-derived growth extract, and the other outlet to a pellet containing an equivalent amount of tissue extract-free Hank's balanced salt solution. At 3 weeks postoperatively, the number of axons and blood vessels in the midportion of implant forks was assessed. The extent of axonal regeneration and blood vessel formation induced were similar to each other and dose-dependent. Results indicate preferential and dose-dependent growth of axons toward pellets containing the retina-derived growth-promoting extract.

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Events in degenerating cat peripheral nerve: induction of Schwann cell S phase and its relation to nerve fibre degeneration.

Severance of a peripheral nerve leads to a characteristic series of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. This study examines the relationship between the spatial-temporal pattern of the induction of the Schwann cell S phase, loss of the structural and functional properties of axolemma, and the clearance of myelin debris in the cat tibial nerve. Nerve transection stimulated a monophasic increase in [3H]thymidine incorporation that peaked at 4 days post-transection throughout an 80-mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibres. Treatment of distal stumps with mitomycin C at the time of nerve transection greatly retarded thymidine incorporation and clearance of myelin debris, but not the time course of axonal degeneration, decline in the synthesis of the major myelin glycoprotein, P0, or the onset of ovoid formation. Nerve transection also greatly reduced the specific uptake of [3H]saxitoxin (STX), a ligand which binds to voltage-sensitive sodium channels. Binding in the distal stump fell precipitously to 20% of the normal at 4 days post-transection, concurrent with the peak of thymidine incorporation. This low level of binding was maintained for periods of up to 70 days, demonstrating that some STX binds to structures other than axons in denervated distal stumps. Prior treatment with mitomycin C delayed the loss of specific STX binding. In conclusion, these studies suggest that: Schwann cell DNA replication and/or mitosis regulates other events during Wallerian degeneration, including myelin degeneration, catabolism of P0 and the clearance of sodium channels from nodal axolemma; the decline in P0 synthesis and/or shift to synthesis of less extensively processed P0 is independent of the induction of Schwann cell S phase; and Schwann cells enveloping myelinated axons enter S phase within a 24-h period throughout the entire 80-mm length of distal stump.

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Regeneration of rat optic axons into peripheral nerve grafts.

The regenerative response of myelinated axons of the mammalian central nervous system was investigated by inserting peripheral nerve grafts in the vicinity of traumatized rat optic axons. Peroneal nerve grafts were inserted into crushed optic nerves and assessed for the ability to support optic axon regeneration. Regenerating axons of retinal origin were present in the peripheral nerve grafts several weeks later. Horseradish peroxidase studies indicated that retinal ganglion cells were a source for regenerating nerve fibers.

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Post-traumatic alterations in glutamine synthetase activity in peripheral and central nerves.

Glutamine synthetase (GS) was assessed distal to the site of axonal injury in traumatized rat central (optic) or peripheral (tibial) nerve prior to and during periods of reactive PNS and CNS glial cell hypertrophy. GS activity in crushed optic nerve remained equivalent to that in unoperated control tissue at 2 days postoperatively, but rose by 30% at 7 and 12 days after surgery. In contrast, GS activity in traumatized peripheral nerve was significantly lower than in unoperated controls at 7 and 12 days postoperatively. Administration of mitotic inhibitor (AraC, cytosine arabinofuranoside) prevented significant trauma-induced alterations in GS activity in optic nerves at 7, and in peripheral nerves at 7 and 12 days postoperatively. Results suggest significant alterations in glial/Schwann GS activity after nerve fiber injury and that these alterations can be delayed/prevented by administration of mitotic inhibitors.

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