Optimisation study of α-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes

The production of no-carrier-added (NCA) α-emitter ²¹¹At/^211gPo radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the ²⁰⁹Bi(α,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the γ-emitter ²¹⁰At and its long half-lived α-emitting daughter ²¹⁰Po is optimised and minimised by appropriate choice of energy and energy loss of α particle beam. The measured excitation functions for production of the main radioisotopic impurity ²¹⁰At→²¹⁰Po are compared with theoretical predictions from model calculations performed at ENEA.     

Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes.

The production of no-carrier-added (NCA) alpha-emitter (211)At/(211g)Po radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the (209)Bi(alpha,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the gamma-emitter (210)At and its long half-lived alpha-emitting daughter (210)Po is optimised and minimised by appropriate choice of energy and energy loss of alpha particle beam. The measured excitation functions for production of the main radioisotopic impurity (210)At-->(210)Po are compared with theoretical predictions from model calculations performed at ENEA.     

Aspergillus galactomannan enzyme-linked immunosorbent assay cross-reactivity caused by invasive Geotrichum capitatum

We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan.     

Neurophysiological assessment of the early phases of carpal tunnel syndrome with the inching technique before and during operation.

In 14 patients with early carpal tunnel syndrome, the diagnostic sensitivity of the measurement of the segmental sensory nerve conduction velocity at 1 cm. steps ("inching") was compared with the distal sensory latency and the pre-operative wrist-digit and wrist-palm S.C.V. and with similar measurements made at operation immediately after surgical decompression of the nerve. Before operation, distal sensory latency and wrist-digit S.C.V. were normal in all cases, while wrist-palm S.C.V. was pathological in five patients and inching in all 14 patients. Moreover, inching allowed us to determine the site of the slowing across the carpal tunnel, this being between 1-2 cm. from the distal wrist crease in 57% and between 2-3 cm. in 21% of cases. Focal slowing disappeared immediately after decompression in five patients, as is evident from the intra-operative recordings. Inching is, therefore, the most sensitive diagnostic method in early carpal tunnel syndrome.     

Two cases of periosteal chondroma

One of our 2 cases of periosteal chondroma of the tibia recurred three times before definitive cure, and required extensive radiographic and histologic evaluation to avoid overinterpreting the malignancy. Our experience confirms that marginal excision should be employed.     

The effect of losartan treatment on the response of diabetic cardiomyocytes to ATP depletion

The present work aimed to investigate the effect of losartan treatment of healthy and diabetic rats on cardiomyocyte response to ATP depletion.Cells were isolated from normoglycemic (N) and streptozotocin-injected (55 mg/kg) rats (D) treated or not treated with losartan (20 mg/kg/day in the drinking water; NL and DL, respectively) for 3 weeks. In each group of cells, enzyme activities such as glucose-6-phosphate (G6PDH) and glycerol-3-phosphate dehydrogenases (G3PDH), lactate/pyruvate, glycogen levels and citrate synthase were measured as an index of glycolytic dysregulation and mitochondrial mass, respectively.Cells were then challenged with NaCN (2 mM) in glucose-free Tyrode solution (metabolic intoxication, MI), a protocol to study ischemia at cell level. Under these conditions, the time to contractile failure up to rigor-type hyper-contracture in field-stimulated cells and K_ATP current activation by patch-clamp recordings were measured.In comparison with N and NL, D cells presented higher G6PDH and cytoplasmic G3PDH activities, lactate/pyruvate, glycogen content but similar levels of citrate synthase, and decay time of contraction. When subjected to MI, D cells showed delayed activation of the K_ATP current (25.7 ± 7.1 min; p < 0.001 vs. N and NL), increased time to contractile failure and rigor-type hyper-contracture (p < 0.001 vs. N and NL). In cells from DL rats both functional (time to rigor and to K_ATP current activation) and metabolic parameters, approached values similar to those measured in N and NL cells.These results demonstrate that diabetic cardiomyocytes from rats treated with losartan, maintain the capacity to respond promptly to ATP depletion reaching contractile failure, rigor-type hypercontracture and K_ATP opening with a similar timing of N cells.     

Methylamine-dependent release of nitric oxide and dopamine in the CNS modulates food intake in fasting rats

BACKGROUND AND PURPOSE: Methylamine is an endogenous aliphatic amine exhibiting anorexigenic properties in mice. The aim of this work was to show whether methylamine also modifies feeding behaviour in rats and, if so, to identify the mediator(s) responsible for such effects. EXPERIMENTAL APPROACH: Microdialysis experiments with the probe inserted in the periventricular hypothalamic nucleus were carried out in 12 h starved, freely moving rats. Collected perfusate samples following methylamine injection (i.c.v.) were analysed for nitric oxide by chemiluminescence and for dopamine and 5-hydroxytryptamine content by HPLC. Kv1.6 potassium channel expression was reduced by antisense strategy and this decrease quantified by semi-quantitative RT-PCR analysis. KEY RESULTS: Methylamine showed biphasic dose-related effects on rat feeding. At doses of 15-30 microg per rat, it was hyperphagic whereas higher doses (60-80 microg) were hypophagic. Methylamine stimulated central nitric oxide (+115% vs. basal) following hyperphagic and dopamine release (60% over basal values) at hypophagic doses, respectively. Treatment with L-N(G)-nitro-L-arginine-methyl ester (i.c.v. 2 microg 10 microl(-1)) or with alpha-methyl-p-tyrosine (i.p. 100 mg kg(-1)) before methylamine injection, reduced nitric oxide output and hyperphagia, or dopamine release and hypophagia respectively. Moreover, hypophagia and hyperphagia, as well as nitric oxide and dopamine release were significantly reduced by down-regulating brain Kv1.6 potassium channel expression. CONCLUSIONS AND IMPLICATIONS: The effects of methylamine on feeding depend on the hypothalamic release of nitric oxide and dopamine as a result of interaction at the Kv1.6 channels. The study of methylamine levels in the CNS may provide new perspectives on the physiopathology of alimentary behaviour.     

Molecular characterization of Italian chromosomes carrying the Lepore Boston gene

Hemoglobin Lepore Boston is characterized by abnormal non-alpha-chains that are the product of a fusion delta beta gene originated from an unequal crossing over between misaligned delta and beta genes. The investigation of the restriction fragment length polymorphisms (RFLP) of the beta-globin gene cluster in 18 Italian Lepore Boston chromosomes indicates that the hybrid gene is linked to two RFLP patterns. The majority of chromosomes show a pattern which corresponds to haplotype V and a minority to haplotype I according to Orkin's classification. A single Hb Lepore Boston homozygote was homozygous for haplotype V. The two haplotypes differ only for a single site 3' to the beta cluster. Our data allow the speculation that in Italy the Lepore Boston gene might be the result of multiple recombination events.     

Fludarabine ability to down-regulate Bcl-2 gene product in CD5+ leukaemic B cells: in vitro/in vivo correlations

CD5⁺ B-chronic lymphocytic leukaemia (B-CLL) and mantle cell lymphoma (MCL) in leukaemic phase are characterized by defects in cell death induction that primarily involves the Bcl-2 family of genes. Fludarabine (9-β- D -arabinofuranosyl-2-fluoradenine, F-ara-A) is a potent inducer of apoptosis in CLL cells. This study aimed to determine whether F-ara-A-induced apoptosis might be related to Bcl-2 modifications and to evaluate in vitro/in vivo correlations.   Peripheral blood lymphocytes from eight B-CLL and four leukaemic MCL were cultured in the presence of different concentrations of F-ara-A ±methylprednisolone (MP). F-ara-A down-regulated the expression of Bcl-2 in 5/12 cases. mRNA down-regulation was maximal at 48 h; protein down-regulation was prominent after 48 h. Both events were dose-dependent. The amount of apoptosis was significantly higher in the samples treated with F-ara-A than in those exposed to MP alone. In the seven remaining cases, no Bcl-2 down-regulation was observed after exposure to F-ara-A and the degree of F-ara-A-induced apoptosis overlapped that induced by MP.   The in vivo outcome after treatment with three to six courses of F-ara-A was evaluable in 10 patients: 4/5 cases, whose cells had shown in vitro Bcl-2 down-regulation and prominent apoptosis after exposure to F-ara-A, had a complete response (CR) and a partial response (PR) was observed in the remaining patient. Of the five patients whose cells had shown no in vitro Bcl-2 modulation after exposure to F-ara-A, two had a PR, but the other three did not show any in vivo clinical response.