Physicochemical characterization, the Hirshfeld surface, and biological evaluation of two meloxicam compounding pharmacy samples / 药物分析学报

Meloxicam (MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently be-tween samples. The FTIR and 1H NMR spectra showed characteristic assignments. 13C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph Ⅲ in an experi-mental model of acute inflammation in mice. Our results highlighted the need for complete crystal-lographic characterization and the separation of freely used raw materials in compounding pharmacies, as a routine procedure, to ensure the desired dose/effect.

Factores asociados a sobrepeso y obesidad en estudiantes de educación secundaria / Factors associated with overweight and obesity in high school students

Objetivos: identificar los factores asociados al sobrepeso y obesidad en estudiantes de educación secundaria de una región andina del norte del Perú. Material y métodos: se realizó un estudio transversal en una muestra de 586 participantes procedentes de dos distritos de la región de Cajamarca (Perú). Realizamos la evaluación antropométrica según los estándares de crecimiento infantil de la Organización Mundial de Salud (se clasificó según puntuación z del índice de masa corporal). Se recolectó mediante un cuestionario estructurado información sobre los estilos de vida, consumo de alimentos, actividad física, síntomas depresivos, acoso escolar y percepción del peso. Se realizó un análisis de regresión logística multivariado para identificar las características asociadas. Resultados: la proporción de sobrepeso y obesidad fue de 22,9% y 6,8% de adolescentes, respectivamente. El pertenecer a escuelas públicas resultó un factor protector para sobrepeso (odds ratio ajustada: 0,62; intervalo de confianza del 95%: 0,39 a 0,99) independientemente del género, actividad física y síntomas depresivos. El género masculino (odds ratio ajustada: 2,05; intervalo de confianza del 95%: 1,02 a 4,11) y la baja actividad física (odds ratio ajustada: 4,14; intervalo de confianza del 95%: 1,65 a 10,35) fueron factores de riesgo para obesidad, mientras que pertenecer a escuelas públicas fue factor protector (odds ratio ajustada: 0,43; intervalo de confianza del 95%: 0,20 a 0,92). Conclusiones: el nivel de actividad física es el principal factor asociado con obesidad, por otro lado, los estudiantes de escuelas públicas presentan menor probabilidad de sobrepeso y obesidad. Las escuelas representan entornos para implementar intervenciones de prevención de exceso de peso basadas en el incremento de la actividad física (AU)

Objective: to identify the associated factors to overweight and obesity in students of high school of an Andean region of northern of Peru. Methods: a cross sectional study was performed in a sample of 586 students, residing in two districts of Cajamarca region. We performed the anthropometric evaluation using the standards of child growth of the World Health Organization (using the score z of the body mass index). We applied a structured survey for recollect data of lifestyles, food consumption, physical activity, depressive symptoms questionnaire, bullying and weight perception. A multivariate logistic regression analysis was performed to identify associated characteristics. Results: the percentage of overweight and obesity was 22.9% and 6.8% of adolescents, respectively. Attending public schools was a protective factor for overweight (adjusted OR: 0.62, CI 95%: 0.39 to 0.99) regardless of gender, physical activity and depressive symptoms. Male gender (adjusted OR 2.05, 95% CI: 1.02 to 4.11) and low physical activity (adjusted OR: 4.14, 95% CI: 1.65 to 10.35) were risk factors for obesity, while attending public schools was a protective factor (adjusted OR 0.43, 95% CI: 0.20 to 0.92). Conclusions: the level of physical activity is the main factor associated with obesity; on the other hand, public school students are less likely of overweight and obesity. Schools represent environments to implement preventive interventions of overweight and obesity based on increased physical activity (AU)

Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.

BACKGROUND: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. METHODS: BALB/c Rag2(-/-), Il2rg(-/-) mice were engrafted with CD34(+) or CD133(+) human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. RESULTS: Both CD34(+) or CD133(+) human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. CONCLUSION: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

Nicotine and cotinine affect the release of vasoactive factors by trophoblast cells and human umbilical vein endothelial cells.

OBJECTIVE: To examine nicotine (N) and cotinine (C) effects on trophoblast cells (TCs) and human umbilical vein endothelial cells (HUVEC) secretion of soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sENG), placental growth factor (PlGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF). STUDY DESIGN: Human placentas and umbilical cords were collected from uncomplicated pregnancies at term from a total of 24 non-smoking women with a history of normal blood pressure. TCs and HUVEC were cultured for 24 h with C or N (from 10(-12) to 10(-7) M). MAIN OUTCOME MEASURES: sFlt-1, sENG, PlGF, TGF-beta and VEGF release and messenger RNA (mRNA) expression were evaluated by ELISA and real-time polymerase chain reaction (PCR), respectively. RESULTS: N and C reduced sFlt-1, sENG and PlGF release by TCs and TGF-beta release by HUVEC. Conversely, N and C increased PlGF secretion, while N alone increased sFlt-1 release by HUVEC. N and C were able to modulate VEGF mRNA expression in HUVEC. CONCLUSIONS: Our results suggest that N and C affect the balance of some important vasoactive factors released by TCs and HUVEC. This might be one of the possible mechanism through which smoke reduces the risk of hypertensive disorders during pregnancy as well as contributes to the well known detrimental effects of smoking on fetal development.

Characterization of a 2D ion chamber array for the verification of radiotherapy treatments.

In this study we investigated the characteristics of a commercial ion chamber array and its performance in the verification of radiotherapy plans. The device was the 2D Array Seven29 model (PTW, Freiburg, Germany). This is a two-dimensional detector array with 729 ionization chambers uniformly arranged in a 27 x 27 matrix with an active area of 27 x 27 cm(2). The detector short-, medium- and long-term reproducibility have been tested through an extensive set of repeated measurements. Short-term reproducibility was well within 0.2%. Medium- and long-term reproducibility were within 1%, including set-up reproducibility errors and linac output fluctuations. Dose linearity was also assessed. The system response to dose was verified to be linear within the range 2-500 MU. Output factors matched very well pinpoint chamber measurements performed in the same experimental conditions with a maximum local percentage difference of 0.4%. Furthermore, the 2D Array sensitivity to millimetric collimator positional changes and to perturbation effect of irradiated area was tested. The comparison with ion chamber data carried out in water was very satisfying. Finally, measurements of wedge-modulated fields and IMRT beam sequence matched very well ion chamber dose profiles acquired in a water tank. The extensive tests performed in this investigation show that the 2D Array Seven29 is a reliable and accurate dosimeter and that it could be a useful tool for the quality assurance and the verification of radiotherapy plans.

Denitrification in tertiary filtration: application of an up-flow filter.

The present paper shows the results obtained through an experimental work performed at the wastewater treatment plant of Rome, aimed at studying the performances of a tertiary filter regarding combined removal of suspended solids, COD, and nitrates. The up-flow sand filter was fed by the effluent coming from the secondary settling tank of the plant. The filter bed height was of 80 cm of silica sand. After a start up period, a study of particulate and soluble COD removal process was made, to establish the need of methanol in the denitrification process. Total COD removal efficiency was 60% on average, 55% due by soluble COD removal and 5% by particulate one. In the last phase of the experimental activity methanol was fed as carbon source, sodium sulfite was supplied to produce anoxic environment within the filter and the denitrification efficiency was studied. Nitrates removal rates after an acclimation period of 10 days increased up to 60%, with an effluent NO3-N of 8 mg/L. Denitrification rate was 2.4 kg/m3 d for water temperatures of 25 degrees C. Regarding methanol demand and biologic kinetics, the biomass yield coefficient was 0.3 kg(COD-X)/kg(me). Consequently 2.7 kg of methanol was required per kilogram of denitrified nitrogen.

[Carotid stenosis with contralateral occlusion. Surgical indications and results]. / Stenosi carotidea con occlusione controlaterale. Indicazioni chirurgiche e risultati.

Recent American and European trials have clearly defined that surgery provides best treatment for unilateral critical stenosis of internal carotid artery. Isolated reports seem to confirm this trend also in cases with carotid critical stenosis with controlateral occlusion, even if a major surgical risk may be expected. In our experience in the last two years, out of 96 carotid enderterectomies 20 presented a controlateral occlusion. After routine pre-operative assessment, with particular regard to DSA "cross-filling" study, intervention has been performed under general anesthesia with BP+EEG cerebral monitoring in both groups of patients. In the non occluded group temporary shunt has been used in 19.7% of cases, in occluded the incident of shunting was 40%. Operative morbidity and mortality in the second group was surprisingly absent, with cumulative 4.1% complication rate. Our experience confirms that risks and results in carotid endoarterectomy are similar in both groups of patients.

The role of transplantation in small hepatocellular carcinoma complicating cirrhosis of the liver.

Of 176 hepatic transplants performed from 1986 to December 1992, 27 patients had small hepatocellular carcinoma (< or = 5 centimeters) complicating cirrhosis of the liver. All patients were asymptomatic for the hepatic malignancy and the diagnosis was established in each instance preoperatively by means of serial sonographic scans and alpha-fetoprotein levels. Cirrhosis was classified as Child's A in eight instances, as Child's B in 16 and Child C's in three. The cause was alcoholic in three patients, posthepatitic in 21 patients (eight hepatitis B virus [HBV] positive and 13 hepatitis C virus [HCV] positive) and undetermined in three. The in-hospital mortality rate was 11 percent (three of 27). Additionally, five patients died at different intervals after transplantation: only two died of neoplastic recurrence at 12 and 32 months, respectively (7.4 percent rate). Actuarial survival rates were 82 percent at one year and 71 percent at three years, with a mean follow-up period of 32 months (range six to 78 months). Morbidity related to the procedure was a relevant problem: 21 percent of the patients had prompt resumption of normal life while 37 percent required repeated hospitalization and 42 percent required strict control on an outpatient basis. The most frequent problem was HBV or HCV reinfection of the grafted liver, which occurred in 42 percent. Based on this experience, transplantation of the liver has shown an excellent oncologic accuracy for small hepatocellular carcinoma in cirrhosis of the liver, thus representing the most rational surgical procedure for patients with Child's B and Child's C cirrhosis classification. The relevant mortality and morbidity rates, strictly related to this procedure, suggest other options as more appropriate in those with Child A cirrhosis at this time.

Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report.

Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3-5 and maintaining parenteral whole-blood trough levels at 200-300 ng/ml during the first month and at 150-250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long-term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow-up after randomization was 6 months (6-27 months). Liver biochemistry was checked at regular intervals throughout the follow-up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long-term therapy. No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid-related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients and may be successfully accomplished in almost all patients.

Dysarthria and cerebellar ataxia: late occurrence of severe neurotoxicity in a liver transplant recipient.

Neurological complications of cyclosporin (CyA) therapy are frequent, usually occurring within the 1st month after transplantation. Though leukoencephalopathy is one of them, it is rarely documented. Here we report the case of an anti-HCV-positive patient with cirrhosis who underwent liver transplantation and developed cyclosporin-induced leukoencephalopathy. The presenting symptoms were dysarthria, difficulty walking, and dysphagia. They were first noted 6 months after transplantation in association with an episode of recurrent HCV acute hepatitis. White matter abnormalities were evident on computed tomography (CT) scanning and magnetic resonance (MR) imaging. This condition improved to some degree after cyclosporin withdrawal. To our knowledge this is the second reported case of CyA neurotoxicity occurring late after liver transplantation. Moreover, the association with acute hepatitis suggests the possibility of graft dysfunction as a contributing and triggering factor.

Somatomedin C (IGF I) plasma levels after orthotopic liver transplantation (OLT) in end-stage cirrhotic patients.

Insulin-like growth factors [IGF I and II or somatomedins (SMS)] are polypeptides chemically and biologically correlated with insulin. The main source of synthetic activity and secretion is the liver, although many other tissues have been demonstrated to synthesize SMS. In the circulation, they are not present in a free form, but are mostly bound to a specific carrier protein independently synthesized in the liver. Hepatic or extrahepatic storage organs have not been demonstrated; the half life of the SMS-binding protein complex is between 3 and 4. Synthesis of SMS is regulated by GH, insulin, thyroxine and nutrition (caloric and protein intake, and nitrogen balance). The role of corticosteroids is still a matter of debate: in patients treated with steroids SMS blood levels have been shown to be within normal limits, while biological activity has been demonstrated to be significantly reduced by SMS inhibitors, probably induced by corticosteroid therapy. The biological properties of SMS are related to their structural homology with insulin, and can be summarized as follows: A. Insulin-like activity (glucose oxidation, lipogenesis, glycogen synthesis, inhibition of lipolysis and glycogenolysis); B. Sulphation activity (incorporation of sulphate and leucine into glycosaminglycans of the cartilage); C. Stimulation of fibroblast multiplication; D. Amplification of other hormone activities (GH); E. Complementary anabolic activity with insulin. Low levels of SMS have been demonstrated in hypopituitarism (secondary) or in other diseases independent of GH reduced secretion (primary) such as malnutrition, malabsorption, acute or chronic liver failure and uraemia. Negative nitrogen balance, hypocaloric and/or low protein diets are usually correlated with low levels of SMS. Recently, Schalch et al. reported on the role of orthotopic liver transplantation (OLT) in normalizing SMS blood levels in a group of end-stage liver diseased patients. This preliminary paper deals with changes in IGF-I plasma levels (somatomedin C) in a group of patients affected by end-stage liver cirrhosis before and after OLT.

Liver transplantation for small HCC in cirrhosis.

Segmental liver resection is generally considered the treatment of choice for small HCC in cirrhotic livers. Although in selected patients with small encapsulated nodules and low alpha-fetoprotein levels long-term survival can be expected after resection, Western experience is still limited, and follow-up studies too short so that the data presently available cannot be considered satisfactory. The true value of alcoholization as a possible alternative therapy in these patients is still to be ascertained. When using these treatment modalities, the major problem is the high tumour recurrence within the liver. Three main reasons could explain these clinical observations: 1. inadequate resection of the original tumor; 2. unrecognized multifocal HCC; 3. newly generated tumours in the remnant cirrhotic parenchyma. The rationale for liver transplantation is the oncological accuracy of the ablation of the liver, and the possibility of a simultaneous cure of the associated cirrhosis. In our programme of liver transplantation, begun in 1985, we accepted as an indication small HCC in cirrhotic livers. We present here our initial experience with 19 cases.