Optokinetic analysis of gait cycle during walking with 1 cm- and 2 cm-high heel lifts.

The use of orthotic heel lifts is proposed in many cases of Achilles tendon disorders as a first-line or conservative treatment. The use of heeled shoes induces a plantar flexion of the ankle joint with a consequent decrease in the tension forces acting onto the triceps surae. The question to address is how high must the heel be? Gait cycle using 1 cm- and 2 cm-high heel lifts was examined. Each measurement included kinetic and kinematic data on angular variation and moments and power at the hip, knee and foot. The study included 14 healthy subjects (5 males, 9 females) between 20 and 35 years of age. The data provided by the analysis of the force plate curve showed a statistically significant change in some parameters (plate forces, knee moments) which were deemed useful in the analysis of load transfer modalities. A very significant decrease (p=0.0001) was found in the amplitude of the curve expressing the force produced by the whole limb in response to ground reaction forces. This is expressed by a decrease in minimum values, suggesting a lower degree of energy absorption at heel strike, as well as maximum values reflecting the amount of energy generated at push off. This might suggest that by reducing energy absorption by the whole limb a 2-cm heel lift would have a protective effect for those muscles that are most significantly involved in this function, such as the tibiotarsal complex (triceps surae) and the knee complex (rectus femoris).

In vitro exposure of human chondrocytes to pulsed electromagnetic fields.

The effect of pulsed electromagnetic fields (PEMFs) on the proliferation and survival of matrix-induced autologous chondrocyte implantation (MACI)-derived cells was studied to ascertain the healing potential of PEMFs. MACI-derived cells were taken from cartilage biopsies 6 months after surgery and cultured. No dedifferentiation towards the fibro- blastic phenotype occurred, indicating the success of the surgical implantation. The MACI-derived cultured chondrocytes were exposed to 12 h/day (short term) or 4 h/day (long term) PEMFs exposure (magnetic field intensity, 2 mT; frequency, 75 Hz) and proliferation rate determined by flow cytometric analysis. The PEMFs exposure elicited a significant increase of cell number in the SG2M cell cycle phase. Moreover, cells isolated from MACI scaffolds showed the presence of collagen type II, a typical marker of chondrocyte functionality. The results show that MACI membranes represent an optimal bioengineering device to support chondrocyte growth and proliferation in surgical implants. The surgical implant of MACI combined with physiotherapy is suggested as a promising approach for a faster and safer treatment of cartilage traumatic lesions.

A finite element method comparison of wear in two metal-on-metal total hip prostheses.

The contact mechanics of two metal-on-metal (MOM) total hip prostheses was studied by means of the finite element method (FEM). The purpose of the work was to compare two total hip replacements (Durom and Metasul) with regard to the amount of wear debris released. Wear on the bearing surfaces was evaluated following Reye hypotheses from the pressure distribution, computed by means of three-dimensional FEM models; an approximate analytical model based on Hertz contact theory has also been developed and discussed. The results show that in the dry friction condition the Durom joint releases almost twice as much wear volume as produced by the Metasul joint. Therefore, while Durom implants can improve hip stability by increasing the prosthetic impingement-free range of motion (PIF-ROM), Metasul prostheses can be a valuable solution whenever wear represents a critical choice factor.

Percutaneous repair of the Achilles tendon in athletes.

The rupture of the Achilles tendon during amateur or professional sport-related activities is becoming more frequent, as is the request for treatments that enable the fastest possible recovery. This study includes 30 patients who sustained rupture of the Achilles tendon during various sport activities; for the last five years we have performed percutaneous suture repair by means of two parallel Dacron threads equipped with a harpoon and a malleable needle. This method alone enables immediate mobilization and an early load, preserves the blood supply of the paratenon, benefits from the motion which accelerates repair, without the well known complications produced both by the non-operative and by open surgical treatments. Excellent results have been achieved and all patients returned to their pre-injury level of sports activity after 120 to 150 days.

A new protein antidenaturant agent, bindarit, reduces secondary phase of adjuvant arthritis in rats.

Bindarit (or 2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid) reduces heat induced denaturation of bovine and rat serum albumin in vitro (EC50 = 8.5 and 65 micrograms/ml, respectively) and inhibits heat induced serum albumin denaturation after in vivo (12.5-25-50 mg/kg po) administration in rats. To assess the relationship between protein denaturation and the development of chronic inflammatory diseases, the drug (0.5 or 0.12% medicated diet) was studied in comparison with indomethacin (1 mg/kg po daily) in rats injected with complete Freund's adjuvant. Bindarit appeared different from aspirin-like drugs, antiinflammatory steroids and immunosuppressants because it does not reduce primary inflammation of arthritic rats and was shown to be completely inactive on cyclo and lipooxygenase activity in vitro and on immune reactions of mice in vivo. Nevertheless, the drug strongly reduced the development of the secondary phase of adjuvant induced arthritis. The most significant effect of bindarit in this phase was a strong inhibition of serum albumin denaturation in arthritic rats. Assessment of both electrophoretic and quantitative changes suggests that the reduction of albumin during inflammation is due, at least in part, to a denaturation of native albumin, which loses its electrophoretic mobility. The involvement of protein denaturation in the production of new antigenic determinants, their pathogenic relevance in the development of adjuvant arthritis and the possibility that protein stabilization by bindarit could be the mechanism of action of the drug are discussed.

Validation of a HPLC method for the determination of bendazac and its main metabolite 5-hydroxybendazac in human plasma.

The purpose of this study was to validate an analytical method for the determination of bendazac and its main metabolite 5-hydroxybendazac in human plasma. The results obtained indicate that the method is reproducible, accurate, precise, sensitive and specific for the measurement of bendazac and 5-hydroxybendazac in the human plasma. Therefore it can be considered suitable for experimental purposes, routine application for drug monitoring and regulatory requirements.

Validation of a HPLC method for the determination of bendazac and its main metabolite 5-hydroxybendazac in rabbit aqueous humor and its applicability to human aqueous.

The purpose of this study was to validate an analytical method for the determination of bendazac and its main metabolite 5-hydroxybendazac in aqueous humor. The method was validated with rabbit aqueous but it can be used also for human aqueous since no differences between the two matrices were observed. The results obtained indicate that the method is reproducible, accurate, precise, sensitive and specific for the measurement of bendazac and 5-hydroxybendazac in the aqueous humor. Therefore it can be considered suitable for experimental purposes, drug monitoring and adequate for regulatory requirements.

Autoradiographic distribution of brain neurokinin-1/substance P receptors using a highly selective ligand [3H]-[Sar9,Met(O2)11]-substance P.

The autoradiographic distribution of neurokinin (NK)-1 receptors was visualized in the rat brain using the highly selective ligand, [3H]-[Sar9,Met(O2)11]-substance P. This ligand apparently binds to a single class of high affinity (Kd = 1.4 +/- 0.5 nM), low capacity (Bmax = 160 +/- 3.0 fmol/mg protein) sites in rat brain membrane preparations. The ligand selectivity profile reveals that substance P (SP) and unlabeled [Sar9,Met(O2)11]-SP are potent competitors of [3H]-[Sar9,Met(O2)11]-SP binding while NK-2 and NK-3 analogues are virtually inactive demonstrating the selectivity of this radioligand for the NK-1 receptor class. Autoradiographic data show that [3H]-[Sar9,Met(O2)11]-SP binding sites are broadly but discretely distributed in rat brain, the highest densities of sites being located in the external plexiform layer of the olfactory bulb, striatum, olfactory tubercule, amygdala-hippocampal area, endopiriform and entorhinal cortices, superior colliculus, locus coeruleus and substantia gelatinosa of the spinal cord. This distribution is similar, but not identical, to that previously reported for NK-1 sites using less selective ligands such as [125I]Bolton-Hunter SP. For example, some difference in labelling patterns are observed in the hippocampal formation. This could be explained by the existence of NK-1 receptor subtypes, only one of them being recognized by [3H]-[Sar9,Met(O2)11]-SP or by the greater selectivity of this radioligand for NK-1 over NK-2 and NK-3 receptor classes.

Reproducible withdrawal contractions of isolated guinea-pig ileum after brief morphine exposure: effects of clonidine and nifedipine.

Guinea-pig ileum stored for 30 min in Krebs solution and then mounted in Tyrode solution gave reproducible contracture responses to naloxone after brief exposure to morphine. The preparation lasted for several hours and a variety of pharmacological tests could be made. Clonidine, an alpha 2-adrenoceptor agonist, and nifedipine, a calcium channel antagonist, both known to interfere with tolerance and physical dependence, inhibited naloxone withdrawal contractures in a dose related way. Their action seemed to be receptor-mediated since yohimbine and Bay k 8644, respectively, reversed their inhibitory effect.

Time-course of aspirin and salicylate in ocular tissues of rabbits.

The time courses of aspirin and salicylate in plasma and ocular tissues of rabbits were investigated after the i.v. administration of aspirin. Unhydrolyzed aspirin rapidly disappears from plasma and many ocular compartments but persists up to 4 hours in aqueous and vitreous humours. Salicylate decreases in plasma follow an exponential kinetics; in aqueous humour and in vascularized tissues the behaviour is similar but with a half-life longer than in plasma. In the cornea, lens and vitreous humour, the concentration of salicylate reaches a peak between 2 and 4 hours, then it decreases very slowly. Our results show that aspirin is protected from the hydrolytic action of plasmatic esterases in aqueous and vitreous humours but is rapidly hydrolyzed in the cornea and lens by local esterases present in these tissues. It is possible that both aspirin and salicylate leave the eye by means of an active transport. Our results also indicate that salicylate can accumulate in the cornea, lens and retina when aspirin is administered repeatedly.

Effects of dapiprazole, clonidine and yohimbine on the development of dependence and withdrawal behaviour in mice.

There is evidence that central noradrenergic hyperactivity is involved in the manifestation of the major signs and symptoms of the opiate withdrawal syndrome. In order to assess whether or not the noradrenergic system is also implicated in the development of opiate dependence, we studied dapiprazole, an alpha-1 selective adrenoceptor antagonist, clonidine and yohimbine using the acute dependence model in mice. When administered just before naloxone, after dependence development, all three drugs reduce abstinence signs. When injected 15 min before morphine to observe the drugs' effects on the development of dependence, dapiprazole depresses all the symptoms registered while clonidine decreases only jumping, but increases paw and head shakes. None of these drugs affects the naloxone precipitated withdrawal syndrome when injected 1 h before morphine. It is suggested that the noradrenergic system is involved in both the manifestation of the withdrawal syndrome and in the development of opiate dependence. Diapiprazole may be a useful tool in patients and in pharmacological studies of dependence and abstinence.

Ocular distribution of aspirin and salicylate following systematic administration of aspirin to rabbits.

The distribution of aspirin and salicylate 30 min after the intravenous administration of different doses of aspirin has been investigated in the rabbit eye. HPLC enabled a rapid and sensitive determination of both substances. A considerable dose-dependent penetration into all ocular tissues was observed with both aspirin and salicylate. Aspirin concentrations were higher than in plasma in all ocular tissues with the exception of the lens. These results show that an unhydrolysed drug may have a direct local effect by acetylating lens protein or other ocular constituents.

Absorption of bendazac lysine after topical application to the rabbit eye.

A water solution of 0.5% 14C-3-bendazac lysine was administered to the rabbit eye. Following single application to the cornea, the drug was found in different ocular compartments including the lens. Although in the lens the concentrations are lower as compared to the iris, retina ciliary bodies and aqueous humor, they last longer.

Prospective evaluation of percutaneous central venous silastic catheters in newborn infants with birth weights of 510 to 3,920 grams.

With improved neonatal survival, especially of very low birth weight infants, our efforts should be directed toward reduction of morbidity. Sick preterm infants require total parenteral nutrition for prolonged periods of time due to extreme prematurity and feeding intolerance. However, the use of surgically placed Broviac catheters has been associated with a high complication rate. A prospective study of 53 percutaneous central venous Silastic catheterizations for administration of total parenteral nutrition was performed in 45 newborn infants. At the time of catheter insertion, 37 babies weighted less than 1,500 g and 19 weighed less than 1,000 g. Percutaneous central venous catheters were placed successfully the first time in 50 of 55 attempts. In three babies, insertion was successful on second attempt. The catheters remained in place for 25.4 +/- 16.7 days ([mean +/- SD] range two to 80 days). In babies weighing less than 1,000 g, the catheters remained in place for a longer period of time (34.0 +/- 18.0; range 12 to 80 days). Sixty-six percent of the catheters were removed electively. There were four cases of bacteremia (7.5%), and the overall incidence of mechanical complications was 26.4%. We conclude that percutaneous central venous catheters can be used safely and effectively in newborn infants for prolonged administration of total parenteral nutrition, especially in neonates weighing less than 1,000 g.