A telerobotic haptic system for minimally invasive stereotactic neurosurgery.

Medical robotics and computer assisted surgery are feasible and promising applications of robotic technology, whose main goals are surgical augmentation, information enhancement and improved surgical action. Neurosurgery probably presents the most major challenges, and can considerably benefit from the introduction of computers and robots to guide surgical procedures. This paper presents an innovative master-slave haptic robotic system for minimally invasive neurosurgery, which can help surgeons overcome human shortcomings and perform more accurate, repeatable, and reliable stereotactic neurosurgery. The system, named LANS, consists of a slave mechatronic actuator and a haptic master. The slave is designed to move linearly a laser pointer, a biopsy needle or a low-energy X-ray emitter along a pre-planned axis. The tool insertion into the brain is guided by the surgeon through the haptic master which also provides force feedback to the operator. Not only can the haptic master reproduce the contact force between the surgical tool and the treated tissue, but it can also produce virtual forces aimed at assisting surgeons during the operations. Experiments have been conducted to prove the soundness and accuracy of the overall system mechanical design and to assess the effectiveness of the control schemes synthesized for the master and the slave.

Alpha-adrenoceptor-mediated inhibition of acetylcholine release in guinea-pig superior cervical ganglion.

The effect of different substances on the electrically evoked acetylcholine (ACh) output from guinea-pig superior cervical ganglion (SCG) preincubated with [3H]choline was investigated. Forskolin significantly reduced neurotransmitter release and dose-dependently enhanced cyclic AMP (cAMP) levels. Phenylephrine and clonidine, alpha 1-and alpha 2-adrenergic agonists respectively, caused a significant inhibition of ACh output from presynaptic nerve terminals. In the presence of RMI 12330A, phenylephrine but not clonidine failed to reduce neurotransmitter release. These results suggest that cAMP and different alpha-adrenergic receptors are involved in the regulation of cholinergic transmission.

Heterosynaptic facilitation and behavioral sensitization are inhibited by lowering endogenous cAMP in Aplysia.

An adenylate cyclase inhibitor, RMI 12330A, is able to depress cAMP synthesis stimulated by serotonin in the abdominal ganglion of Aplysia depilans and punctata. This substance reversibly blocked the heterosynaptic facilitation, induced by activation of serotonergic pathways, of the EPSP recorded from L7 motoneuron in abdominal ganglion after electrical stimulation of the siphon nerve. RMI 12330A, injected into whole unrestrained animals, inhibited the short-term dishabituation of the siphon withdrawal reflex. These findings demonstrate that the increase of endogenous cAMP in the sensory neurons mediating the gill and siphon withdrawal reflex is an essential step in the mechanism of potentiation of the transmitter output underlying heterosynaptic facilitation and short-term behavioral sensitization.

cAMP-dependent and cAMP-independent modulation of synaptic transmission in guinea-pig superior cervical ganglion.

RMI 12330A dose-dependently inhibits cAMP accumulation induced by PGE2 in guinea-pig superior cervical ganglion (SCG). Norepinephrine (NE) is unable to modify cAMP concentration in the same preparation. On the other hand, both PGE2 and NE block the firing discharge of guinea-pig SCG neurons elicited by electrical stimulation (1 Hz) of the cervical sympathetic trunk. The effect of PGE2, but not that of NE, is prevented by RMI 12330A, suggesting that NE and PGE2 act through different pathways

Role of serotonin and cyclic AMP on facilitation of the fast conducting system activity in the leech Hirudo medicinalis.

In the nervous system of the leech Hirudo medicinalis it has been possible to study short-term plastic changes. Depression and facilitation have been demonstrated in the fast conducting system (FCS) activity; this pathway consists of a chain of electrically linked neurons present in each ganglion. In semi-intact animals or in preparation of nerve cord and segments of body wall, both electrical stimulation of peripheral roots and tactile stimulation of the skin induced, after repetitive stimulation (0.1/s) a prolonged decrement of FCS response. Strong nociceptive stimulation applied onto the head or the body wall produced a sustained facilitation of the waned response. The same potentiation has been observed by perfusing the isolated ganglion with serotonin (5 x 10(-5) M). Such a potentiation is abolished by preincubation with methysergide, an antagonist of serotonin, and with imidazole, a cAMP-phosphodiesterase activator. Such an effect is mimicked by an analog of cAMP, db-cAMP. Simultaneous recordings of both T neurons (intracellularly) and FCS firing discharge showed that, during FCS response decrement, the T cell activity remained unchanged and no modification of conductance occurred, excluding therefore a detectable involvement of sensory neurons in the depression. These results suggest that short-term plastic changes of the FCS of the leech are due to a prolonged potentiation of synaptic transmission as a result of serotonin-mediated increase in cAMP.

Evidence for increased release of prostaglandins of E-type in response to orthodromic stimulation in the guinea-pig superior cervical ganglion.

Prostaglandins of the E type (PGEs) stimulate cyclic adenosine 3',5'-monophosphate (cAMP) biosynthesis both in isolated preparations of rat, guinea-pig and rabbit superior cervical ganglia (SCG) and in calf SCG slices. Electrical stimulation of preganglionic nerve fibers of the guinea-pig SCG remarkably increased PGE release and cAMP biosynthesis. These effects were blocked by reducing the Ca2+ to Mg2+ ratio in the incubation medium. Atropine (1 microM) and phentolamine (10 microM) inhibited PGE biosynthesis and significantly reduced cAMP levels.

[Preliminary observations on in vitro biosynthesis of prostaglandins E in tumor cells and virus transformed cells]. / Osservazioni preliminari sulla biosintesi in vitro di prostaglandine di tipo E in cellule tumorali e trasformate da virus.

Biosynthesis of prostaglandins of E series in BK virus-transformed rabbit-kidney cells (RKBK) and mouse hepatoma cells cultured in vitro with and without exogenous arachidonic acid was determined by radioimmunoassay. Elevated concentrations of prostaglandin E2 were observed in both cell types; moreover, tumor and transformed cells were capable to synthesize higher levels of prostaglandin E2 than normal cells. Mouse hepatoma cells produced more prostaglandins compared to RKBK cells; in addition they seemed less sensitive to inhibition by indomethacin. These data suggest that arachidonic acid metabolism may be another one of the intrinsic biochemical properties that differentiate tumor and virus transformed cells.

Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs.

Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes. Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 microM) or L 8027, a prostaglandin synthetase inhibitor. Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by anti-inflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth.

Ca2+-activated ATPase of rat liver plasma membrane.

Rat liver plasma membranes hydrolyze ATP in the presence of Ca2+. The rate of hydrolysis is different when Mg2+ions are present in the incubation system. Several parameters differentiate Ca2+-ATPase from Mg2+-ATPase: a) the Km of ATP hydrolysis for Ca2+ (2.25 x 10(-4) M) is lower than for Mg2+ (2.14 x 10(-3) M); b) the shape of the activation curve is hyperbolic in the presence of Ca2+ and sigmoid in the presence of Mg2+; c) Mg2+-ATPase shows two different values of activation energy while Ca2+-ATPase presents only a single value; d) Ca2+-ATPase is inhibited, while Mg2+-ATPase is unaffected by cyclic AMP. Ca2+-ATPase is localized on the plasma membrane and is not inhibited by cysteine. It does not hydrolyze substrates different from nucleotides triphosphate, such as glucose-1-phosphate or alpha-glycero-phosphate. The enzyme is probably related to a mechanism of calcium transport.

Isolation and characterization of the plasma membrane from Yoshida hepatoma cells.

Plasma membranes isolated from Yoshida ascites hepatoma AH-130 by a modification of the method of T.K. Ray (Biochim. Biophys. Acta 196:1, 1970), were subfractionated into three fractions having densities (d) 1.12, 1.14 and 1.16 by discontinuous sucrose density-gradient. Membrane subfractions were characterized by electron-microscopy, by assay of marker enzymes and by lipid composition. All subfractions appeared to be essentially free from whole mitochondria, lysosomes and nuclei. Subfraction d 1.16 had the highest 5'-nucleotidase, Mg++-ATPase and (Na+ +K+)-ATPase activities; cytochrome c oxidase was undetectable in any fraction and glucose-6-phosphatase was measurable only in fraction d 1.14 and 1.16. Cyclic AMP phosphodiesterase was nearly equally distributed in the fractions. Adenylate cyclase, 5'-nucleotidase and Mg++-ATPase activities of tumor membrane were lower with respect to liver plasma membrane, while cyclic AMP phosphodiesterase and (Na" +K+)-ATPase were found to have similar activities in the two membrane preparations. With respect to liver membrane, hepatoma membrane contained a higher amount of glycolipids and a higher amount of phospholipids accounted for mainly by sphingomyelin, phosphatidylserine and phosphatidic acid. The possible significance of the decrease of adenylate activity in the hepatoma membrane is briefly discussed.