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The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severity cannot be used as valuable predictors of BUP treatment outcome. High doses appear to predict a better outcome, in term of negative urines, for both METH and BUP, but not in term of retention for BUP patients.

This study monitored the extranuclear endogenous mono-ADP-ribosylation of proteins. At least 10 proteins were ADP-ribosylated in a crude extract from control superior cervical ganglia, and 7 were labeled in control dorsal root ganglia; whereas in the diabetic rat the extent of labeling was reduced. These data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations in the extent of mono-ADP-ribosylation of proteins. This effect was associated with the prevention of substance P-like immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats the extent of labeling was increased. A comparable increase involving the same proteins was triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy, while the silybin effect on mono-ADP-ribosylation of Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.

Objectives The aim of this work was to compare in vitro the aerodynamic behavior of an amikacin sulphate liquid solution after nebulization and an amikacin dry powder (AmikaPS) after aerosolization. AmikaPS, was prepared using a proprietary spray drying technology to construct a powder to inhale having high content of drug and respirability. Methods Amikacin solution for injection was nebulized with Pari Turbo boy equipped with a Pari LC plus cup. AmikaPS powder was loaded in the DPI device (RS01, Plastiape) at the labeled dose of 125 mg of amikacin sulfate. Results The dosage of amikacin solution given off-label by nebulization is 625 mg/twice a day. At the end of the nebulization, it was found that, more than 50% of the amikacin dose (625 mg amikacin sulfate corresponding to 500 mg amikacin base) remained in the ampule, about 20% was dispersed in the environment and only 17.6% of the loaded dose was delivered as aerosol available for inhalation. Thus, since the respirable fraction of this aerosol was 56.3%, the dose to lung after 625 mg nebulization resulted 61.8 mg of amikacin sulfate. The fine particle dose of AmikaPS powder was 63.8 mg of amikacin sulfate. The data indicate that 125 mg of amikacin sulfate powder afford a respirable dose equivalent, or even slightly higher than that obtained by nebulizing 3 mL of solution for injection containing 625 mg of amikacin sulfate. Conclusions The objective of the proposed amikacin product is to offer a valid alternative to the other antibiotics for inhalation, keeping as low as possible the amount of powder to be inhaled by the patient while maximizing the amount of active ingredient deposited in the lung.

In a series of 150 patients with congenital urologic disorders diagnosed in utero and managed in the neonatal period from 1980 to 1985, 48 cases were ureteropelvic junction obstructions. One was a false positive, and 47 were documented pyelocaliceal distension and retention; 12 of them were bilateral. Five cases had a spontaneous resolution. Three had a nephrectomy performed (destroyed kidney). Fifty kidneys have been operated on (Anderson-Hynes dysmembered pyeloplasty). Ninety percent of the cases are reported as clinically, biologically, and radiologically fair. Six percent postoperative complications are reported. The authors pointed out the great interest in neonatal repair of this condition, using microsurgical techniques without stent or nephrostomy. A comparison is made of the overall results with an identical series of older patients operated on during the same period.

Substance P and Met-enkephalin were detected by radioimmunoassay and immunocytochemistry in the rat lumbar spinal cord. The sciatic nerve was lesioned by resecting a piece and the proximal stump was either ligated, for limiting neurite outgrowth, or intraperitoneally sutured, allowing the formation of a large neuroma. Ten days post lesioning both peptide levels dropped approximately 50% and the punctate immunoreactivity decreased in the dorsal horn. Lesioning both sciatic nerves did not accelerate nor increase the extent of peptide loss compared to monolateral lesions. Immunocytochemistry showed that after bilateral lesioning also the punctate immunoreactivity in the dorsal horn decreased less drastically. However, FRAP staining of the dorsal horn decreased according to the lesion paradigms, mono- and bilaterally with the same intensity. Therefore nerve lesions trigger the process, but the peptidergic loss seems intraspinally regulated. In addition, both kinds of abnormal neurite outgrowth similarly altered peptide levels and distribution in the spinal cord. Our data suggest that pain states related to peripheral nerve lesions may be due to opiate peptide loss rather than to neuroma.