Potential of Gene Therapy in Bone Marrow Transplantation

Gene therapy, initiated as a treatment for inherited disorders such as adenosine deaminase deficiency, is now a promising therapeutic strategy for malignancies and other acquired diseases. In particular, in the field of bone marrow transplantation (BMT) for haematological malignancies, the gene transfer of the suicide gene HSV-TK into donor lymphocytes allows control of the severe complication graft-versus-host disease (GvHD). The transfer of the HSV-TK suicide gene confers selective sensitivity to the drug ganciclovir, allowing in vivo elimination of the donor T-cells if severe GvHD occurs. In Italy, the first pilot study on delayed infusion of genetically engineered donor lymphocytes after T-depleted allogeneic BMT documented efficacy of engineered donor lymphocytes in terms of anti-tumour activity and efficiency of the suicide system. GvHD developed in 3 out of 8 patients and was successfully treated by ganciclovir administration.     

Clinicopathological study of familial late infantile Hallervorden-Spatz disease: a particular form of neuroacanthocytosis

The cases of two sisters with late infantile Hallervorden-Spatz disease are reported, one of whom has died. Autopsy of the deceased patient showed typical pallidal lesions, such as axonal spheroids and iron deposits, without involvement of the substantia nigra. Ultrastructural examination revealed that pallidal axonal enlargements consisted of collecition of mitochondria, dense bodies, vesicles and amorphous material. In the living patient, brain MRI showed the classical tiger's eye appearance of the globus pallidus. Retinitis pigmentosa, acanthocytosis and slight neuromuscular involvement with an increase in serum creatine kinase were observed in both subjects. The appearance of the globus pallidus on MRI was in line with the pathological abnormalities. Ultrastructural differences between the principal disorders characterized by neuroaxonal dystrophy are compared and the clinical spectrum and similarities of the different forms of neuroacanthocytosis analysed.     

Caustic ingestion in childhood: current treatment possibilities and their complications

In a review of 15 pediatric patients who had ingested caustic substances, the authors describe the diagnostic and therapeutic procedures to be followed as well as the complications that may occur with their use. The cases reported include 1 esophageal rupture caused by balloon dilatation and 1 recurrent stenosis treated with a silastic tutor.     

Effects of heroin,alone or in combination with other drugs,on the locomotor activity in two inbred strains of mice

The locomotor activity of C57B1/6J and DBA/2J mice was studied, under the influences of heroin, amphetamine, strychnine, or ethanol, and of combinations of the opiate with each one of the other drugs. Heroin treatment was followed by the typical running fit in the C57 mice, while the DBA strain was unaffected. Amphetamine enhanced the activity in the C57 strain only. The combination of heroin with amphetamine or ethanol increased the locomotor activity only in the DBA strain, while heroin + strychnine exerted a clear stimulating effect on the activity of the C57 mice. The strychnine + heroin mixture was more toxic than heroin alone when the lethal doses (LD50) were determined in the 2 strains.     

Effects of nicotine on discrimination learning,consolidation and learned behaviour in two inbred strains of mice

DBA/2J and C57BL/6J mice were injected with nicotine, and tested in a Y water maze in two procedures: the L procedure, corresponding to innate behavior, in which the animals must swim towards the light, and the D procedure, corresponding to the acquisition of a new pattern of behavior, in which they must swim toward the dark. Three sets of experiments were carried out:

1. In the pre-trial experiments, nicotine administration improved the innate tendencies of both strains, while the acquisition of a new behavior was facilitated in the C57 and impaired in the DBA mice.
2. In the post-trial experiments (D procedure), nicotine administration induced clear facilitating effects on the consolidation processes of the C57, while impairing these processes in the DBA strain.
3. The only effect evident, following nicotine administration, before the highest doses were reached, in the trained mice of both strains, was a performance impairment of the DBA mice trained in the L procedure.

     

Effects of hyaluronan on free-radical formation, corneal endothelium damage, and inflammation parameters after phacoemulsification in rabbits.

Free-radical formation may play a role in postoperative complications of phacoemulsification (e.g., corneal endothelium damage from mechanical injury). The present experiments were aimed at investigating whether different molecular weight ranges (2000-2600, 2600-3200, or 3200-3800 kDa) of hyaluronan may influence free radical formation, corneal endothelium damage, and inflammation parameters after phacoemulsification in the rabbit eye. The viscoelastic substance was injected in the anterior chamber of rabbits' eyes before phacoemulsification, at a 2.5% concentration. The formation of free radicals was determined by adding luminol to the irrigation media and measuring the chemoluminescence in eyes. The corneal endothelial damage was evaluated by measuring the corneal central thickness by pachimetry. The inflammation parameters were measured by calculation in aqueous humor of peak levels of leukocytes and prostaglandin E(2) (PGE(2)) and evaluation in uveal tissue of myeloperoxidase activity. Hyaluronan decreased by about 58-60% free-radical formation during phacoemulsification, reduced by about 76-80% modifications in mean corneal thickness and by about 54-61% the corneal endothelial cell loss in all molecular weight ranges used. No difference was found among various molecular weight ranges. The highest molecular weight range showed to be more potent than the lowest range for reduced number of inflammation cells and level of PGE(2) in aqueous humor. Thus, hyaluronan reduces free-radical formation, exerts protection on the corneal endothelium and exerts anti-inflammation properties after phacoemulsification in rabbits. The latter effect seems to depend on the molecular weight of the substance.