Serum levels of neuropeptide Y in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the double-blind randomized controlled PULSAR study).

OBJECTIVE: Modulation of glutamatergic neurotransmission in schizophrenia by sarcosine leads to a reduction in primary negative symptoms, while its metabolic profile is safe. In order to extend research in the area, we assessed serum levels of neuropeptide Y (NPY), a hypothalamic hormone related to anxiety and depression, also involved in mechanisms inducing weight gain. Additionally, we analyzed associations between NPY concentrations and its changes with severity of symptoms and metabolic parameters. METHODS: A prospective 6-month, randomized, double-blind placebo-controlled trial was completed by 57 subjects with chronic schizophrenia with predominant negative symptoms and stable antipsychotic treatment. The participants received 2 g of sarcosine (n = 28) or placebo (n = 29) daily. We assessed serum NPY concentrations and severity of symptoms (with the Positive and Negative Syndrome Scale [PANSS] and Calgary Depression Scale for Schizophrenia) at the beginning of the study, after 6 weeks and 6 months. RESULTS: Sarcosine did not affect NPY levels in all time points. The highest decrease in NPY concentrations was observed in the subjects who were initially depressed, who became euthymic at the last visit. We noticed an improvement in the total PANSS score, and negative symptom and general psychopathology subscales in the sarcosine group, however, without any correlation with NPY levels. CONCLUSION: The use of sarcosine does not change NPY levels. Peripheral NPY concentrations may be related to depressive symptoms in schizophrenia.

Criterios clínicos y radiológicos en la decisión terapéutica del reflujo vesicoureteral. Un análisis retrospectivo de nuestra experiencia / Clinical and radiological criteria for the therapeutic decision for vesicoureteral reflux. Retrospective analysis of our experience

Objetivo: Establecer, en base a nuestra experiencia, unos esquemas terapéuticos del reflujo vesicoureteral en el niño, apoyándonos en resultados clínicos y radiológicos, observando cómo han ido evolucionando las indicaciones y tiempos de tratamiento con el advenimiento de las técnicas endoscópicas. Métodos: Se han analizado los pacientes con reflujo vesicoureteral tratados en dos periodos de similar duración: el primero (106 pacientes), entre 1995 y marzo 2001 (fecha en que se introdujeron las técnicas endoscópicas); el segundo, (138 pacientes), desde esa fecha hasta marzo de 2007. En todos los pacientes se estudiaron variables clínicas, diagnósticas y terapéuticas, así como el resultado obtenido. Resultados: El número de pacientes tratados aumentó en el segundo período, en él disminuyó ostensiblemente (de 24 a 7) el número de pacientes que requirieron reimplantación vesicoureteral. La proporción de éxitos del tratamiento endoscópico ascendió al 94,9%, no apreciándose diferencias significativas en función de la edad o el grado de reflujo, aunque se observa un mayor porcentaje de fracasos en niños menores de 3 años y en reflujos de alto grado. La presencia de malformaciones asociadas no se relacionó con una peor evolución tras el tratamiento. Conclusiones: En aquellos reflujos donde el tratamiento médico no ha sido eficaz, persistiendo o empeorando el mismo, y como alternativa a la cirugía abierta (con buenos resultados pero con una morbilidad no desdeñable), el tratamiento endoscópico se convierte en una alternativa de eficacia similar y mínimamente agresiva. Proponemos un esquema orientativo para establecer las indicaciones de cada estrategia terapéutica en función del grado de reflujo y su evolución clínica (AU)

Objectives: According to our experience, we present a proposal for the treatment of vesicoureteral reflux, based on both clinical and radiological evidences. We also describe how the introduction of endoscopic procedures has influenced the evolution of treatment indications as well as the time intervals for treatment. Methods: We have analysed all cases of vesicoureteral reflux treated in our Department in two periods of similar length: The first one (106 patients) comprised from 1995 to March 2001 (when endoscopic procedures were introduced). The second one (138 patients), comprised from March, 2001 to March 2007. Clinical, diagnostic, therapeutic and outcome-related variables were studied for all cases. Results: The number of patients was higher in the se-cond period. In this period the number of cases requiring ureteral reimplantation decreased with respect to the first one (from 24 to 7). The success rate with endoscopic treatment reached 94,9%, with no significant differences regarding age or grade of reflux, although higher rates of failures were observed in children aged less than 3 years old and in high-grade reflux. The association of reflux with other malformations was not related with a worse evolution after treatment. Conclusions: Endoscopic treatment, due to its similar efficacy and low aggressiveness, should be considered a valid alternative to open surgery (which offers good results but non-negligible comorbidity) for persistent reflux in which medical treatment has not been useful. We propose a tentative therapeutic scheme to establish the indications for each type of treatment depending on the grade of reflux and its clinical evolution (AU)

DEAE-Dextran in the treatment of primary hypercholesterolemia and/or hypercholesterolemia combined with hypertriglyceridemia. A multicentric randomized study on the efficacy of DEAE-Dextran compared with Cholestyramine.

This study was carried out to verify the therapeutic homogeneity between DEAE-Dextran and Cholestyramine. Blood levels of total cholesterol, HDL, LDL and triglycerides were evaluated in 202 patients affected by dyslipidemia and treated with DEAD-D at 2.5 g/day or with Cholestyramine at 12 g/day for 30 days. At the end of treatment both drugs caused significant reduction of total cholesterol, LDL and triglycerides blood levels; DEAD-D was generally more effective than Cholestyramine, in particular on triglycerides values (30.6% and 13.7% of reduction respectively), and produced also a significant increase in HDL cholesterol, differently from Cholestyramine that was ineffective on this parameter.

Effect of topically applied charged particles on healing of colonic anastomoses.

HYPOTHESIS: Various forms of electrical stimulation can improve wound healing in different tissues, but their application to gastrointestinal tract healing has not been investigated. We assumed that positively charged diethylaminoethyl cross-linked dextran bead (diethylaminoethyl Sephadex [DEAE-S]) particles would have a beneficial effect on the healing of colonic anastomoses. DESIGN: Experimental animal study. SETTING: Animal research laboratory of a university hospital. ANIMALS: Forty female Wistar albino rats. INTERVENTIONS: Right colonic transection and anastomosis was performed in 5 animal groups. The control group received no treatment; the placebo group, methylcellulose gel; and the DEAE-S group, DEAE-S in methyl cellulose gel applied topically around the anastomoses. The fecal peritonitis (FP) group underwent cecal ligation and perforation simultaneously with the anastomosis to cause FP; the FP + DEAE-S group also received DEAE-S applied around the anastomoses. MAIN OUTCOME MEASURES: After the completion of postoperative day 4, all rats were killed. Anastomotic bursting pressures and hydroxyproline concentrations in perianastomotic tissue were measured and compared. RESULTS: Mean bursting pressures were 115.1 mm Hg in the control group, 113.6 mm Hg in the placebo group, 159.4 mm Hg in the DEAE-S group, 62.8 mm Hg in the FP group, and 121.1 mm Hg in the FP + DEAE-S group (P =.001, 1-way analysis of variance [ANOVA]). The differences between the control vs DEAE-S groups, placebo vs DEAE-S groups, and FP vs FP + DEAE-S groups were significant (P<.05, t test). Mean hydroxyproline concentrations were 5.2 microg/mg in the control group, 4.9 microg/mg in the placebo group, 5.6 microg/mg in the DEAE-S group, 4.5 microg/mg in the FP group, and 5.4 microg/mg in the FP + DEAE-S group (P =.09, 1-way ANOVA). The difference between the FP and FP + DEAE-S groups was significant (P =.04, t test). CONCLUSIONS: A positively charged particle, DEAE-S, improves healing of colonic anastomoses in healthy rats and in rats with FP. This inexpensive, nontoxic material is easily applied and deserves further evaluation in gastrointestinal tract healing.

Potentiation of gene transfer to the mouse lung by complexes of adenovirus vector and polycations improves therapeutic potential.

Recombinant adenovirus (Ad) vectors are being considered for in vivo delivery of various therapeutic genes. One limiting factor in the development of Ad-based gene therapy is the low efficiency of gene transfer to target tissues such as vascular endothelium, smooth muscle, and airway epithelium. Complexing Ad vector with various polycations has been shown to enhance transduction of cell lines otherwise resistant to Ad infection in vitro. On the basis of this observation, the activity of Ad/polycation complexes was tested in vivo in the mouse lung. The results indicated that several polycations were capable of enhancing transduction of mouse respiratory epithelium, leading to a 1-2 log increase in levels of transgene expression. Poly-L-lysine (PLL) and DEAE-dextran were examined further and were found to increase Ad-mediated gene transfer without any additional toxicity as assessed histologically or through the measurement of inflammatory cytokines in bronchoalveolar lavages. The two polycations also failed to affect the humoral response against Ad vector and were themselves nonimmunogenic under conditions leading to enhanced gene transfer. Moreover, the ability to use reduced doses of vector complexed with polycations resulted in lower levels of Ad-specific antibodies and, thereby, improved readministration of vector. These results suggest that complexing Ad vectors with polycations has the potential to improve the therapeutic index by increasing transgene expression while reducing unwanted responses associated with high doses of vector.

Effects of a positively charged biomaterial for dermal and subcutaneous augmentation.

Based on previous experimental connective tissue work, the use of a positively charged dextran-based biomaterial in subcutaneous tissue sites was evaluated. After hydration with saline, the biomaterial was injected beneath the abdominal skin in rats. A robust macrophage response was initially seen at 30 days without acute inflammation. By one year postoperatively, extensive intermaterial fibroblast and collagen ingrowth had occurred. No evidence of a foreign-body or chronic inflammatory response was seen. These preliminary findings suggest good tissue compatibility of this biomaterial and suggests that when combined with a biocompatible liquid medium, the potential for development of a bioactive dermal and subcutaneous injectable substance exists.

[Hyperlipidemia: physiopathology and our experience in the ambulatory care of 3 groups of patients undergoing blood lipid normalization treatment]. / Le iperlipidemie. Fisiopatologia e nostre esperienze ambulatoriali su tre gruppi di pazienti sottoposti a trattamento normolipemizzante.

The authors tested the efficacy of three different lipid-lowering drugs in subjects with more or less severe alterations of the lipoprotein pattern. All subjects were submitted to blood tests prior to and at the end of treatment with special attention to the trend of the lipid pattern, assaying cholesterol, HDL, LDL, triglyceride, total lipid blood levels and lipid electrophoresis. The drugs employed were: pantothenic acid, sulodexide, and DEAE-dextran.

[The treatment of refractory hyperlipoproteinemias]. / Il trattamento delle iperlipoproteinemie resistenti.

The authors have studied a group of 25 patients treated with an HMG-CoA reductase inhibitor associated with DEAE-dextran, a safe and useful drug for the treatment of dyslipidemia. The patients were selected from a group of subjects previously submitted to long-term treatment with an HMG-CoA reductase inhibitor only who had failed to achieve normal cholesterol blood levels. The combined treatment with DEAE-dextran (1.5 g 3 times daily) and simvastatin (20 mg once daily) for 90 days lead to a further significant decrease in cholesterol and triglyceride blood levels. These findings confirm the validity of the association of an ion exchange resin with an HMG-CoA reductase inhibitor in the treatment of refractory dyslipidemias.

[A large case load of patients with dyslipidemia: effects of treatment with deae-dextran]. / Studio su un'ampia casistica di soggetti dislipidemici: effetti del trattamento con il deae-destrano.

The authors report the results of an open trial in 859 dyslipidemic patients, performed with the cooperation of general practitioners, treated with isocaloric diet and daily doses of 3 g deae-dextran for 3 months. Deae-dextran was effective in reducing cholesterol and triglyceride blood levels and in controlling body weight. The drug was very well tolerated and no significant side effects were registered during treatment with deae-dextran.

[Preliminary results of an open study on the effects of DEAE-dextran on various lipid metabolism parameters in dyslipidemic subjects]. / Prime osservazioni di uno studio aperto sugli effetti del DEAE-destrano su alcuni parametri lipometabolici di soggetti dislipidemici.

The authors report the results of a study of 1963 patients treated with daily doses of 2 g DEAE-dextran. This was an open trial intended to evaluate the evolution of several biohumoral parameters under treatment for dyslipidemias. Statistically significant results were obtained for cholesterol blood level, triglycerides and body weight, as well as a favorable trend for HDL-cholesterol. Side effects or untoward reactions to DEAE-dextran were not observed.