The ultraviolet derivative spectrophotometric determination of neutral liposome-entrapped beta-lactam antibiotics

A simple, non-invasive spectrophotometric assay to measure the concentration of some beta-lactam antibiotics in turbid solutions containing liposomes was carried out. Since zero-order spectra gave strong interference because of sample turbidity, derivative spectrophotometry was used to enhance the spectral details. Derivative spectra showed bands in the ultraviolet region due to the presence of the cephalosporin and penicillin beta-lactams. A linear relationship between derivative amplitudes and antibiotic concentration was found when antibiotic-containing liposome solutions were measured. A saturative trend in the liposome-encapsulation was observed. The antibiotic entrapment was lowered by increasing the cholesterol-phospholipid ratio in the mixture used for liposome preparation. After treatment of antibiotic-loaded liposomes with beta-lactamase, a hydrolytic enzyme specific for beta-lactams, the remaining antibiotic concentration decreased significantly, showing that some of the antibiotic was retained on the outer surface of the vesicles.     

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.     

Effects of long-term acetyl-L-carnitine administration in rats--II: Protection against the disrupting effect of stress on the acquisition of appetitive behavior.

Long-term acetyl-L-carnitine (ALCAR) administration prevents the development of escape deficit produced by acute exposure to unavoidable stress. However, it does not revert the escape deficit sustained by chronic stress exposure. Rats exposed to chronic stress show a low dopamine (DA) output in the nucleus accumbens shell (NAcS) and do not acquire an appetitive behavior sustained by the earning of vanilla sugar (VS) made contingent on the choice of one of the two divergent arms of a Y-maze (VS-sustained appetitive behavior, VAB), while control rats consistently do. The present study shows that ALCAR treatment in rats exposed to a 7-day stress protocol prevented a decrease in DA output in the NAcS and medial prefrontal cortex (mPFC) of rats, and that it strengthened the DA response to VS consummation in the same two areas. Moreover, rats treated with long-term ALCAR or exposed to chronic stress while treated with ALCAR acquired VAB as efficiently as control rats. Moreover, VAB acquisition in stressed rats treated with ALCAR coincided with the reversal of the deficits in escape and in dopaminergic transmission in the NAcS. Thus, repeated ALCAR treatment preserved the DA response to VS in chronically stressed rats and this effect appeared to be predictive of the rat's competence to acquire VAB.     

Glycosaminoglycan Supplementation Promotes Nerve Regeneration and Muscle Reinnervation

This study shows that treatment of rats with exogenous glycosaminoglycans stimulates peripheral nerve regeneration, increases the abundance of mRNAs for myelin proteins and promotes muscle reinnervation. After the sciatic nerve had been crushed the number of regenerating axons in the distal stump was markedly and highly significantly increased by glycosaminoglycan treatment throughout the experimental period. The increased number of axons was correlated with increased axon and fibre (axon + myelin) diameter. The abundance of mRNAs for P_o protein and myelin basic protein of regenerating nerves was also affected by treatment with glycosaminoglycans. The increase in mRNA was also observed in the contralateral unlesioned nerve. Such a phenomenon did not occur in saline-treated rats. Glycosaminoglycan treatment markedly increased the number of muscle fibres reinnervated and accelerated the restoration of muscle twitch tension elicited by nerve stimulation. The effect was particularly evident during the early stages (16 and 21 days after nerve crush) of muscle reinnervation.     

Factors controlling the selectivity and efficiency of tumour damage in photodynamic therapy

The scope and potential of the photodynamic therapy of tumors can be enhanced through an adequate control of the factors which improve the selectivity of tumour targeting by the systemically injected photosensitizer and increase the efficiency of photosensitized tumour damage. Promising results are obtained by using hydrophobic photosensitizers which can be specifically transported and released to the tumour by serum lipoproteins, especially low-density lipoproteins. The photosensitizer molecule should possess those structural features which induce a high probability of photoactivation by 700–800 nm light, as well as a high yield of long-lived triplet state. The use of liposome-delivered Zn-phthalocyanine as a second generation phototherapeutic agent for tumours is proposed.     

Effect of prone positioning on the survival of patients with acute respiratory failure

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.     

Effect of sulglycotide treatment on cell kinetics alterations induced by aspirin in humans

The effect on gastric epithelial cell proliferation of small doses of aspirin was evaluated in 9 healthy volunteers, with or without administration of sulglycotide, a sulfated glycopeptide with cytoprotective properties. Cell kinetics study was performed by incubation of gastric biopsies with bromodeoxyuridine (BrdU) and immunohistochemistry. A decrease of BrdU-labeling index and a shortening of the height of gastric columns were observed after treatment with aspirin and placebo. No variations were observed after treatment with aspirin and sulglycotide. A decrease of the epithelial cell renewal could be one of the damaging effects of aspirin on the gastric mucosa. The treatment with sulglycotide seems to be effective to prevent this alteration.