Development of an optimized freeze-drying protocol for OM-PBAE nucleic acid polyplexes.

Long-term stability of polyplexes used for biomedical purposes is an objective envisaged by any research group developing this kind of nanoformulations. However, since biodegradable polymers such as oligopeptide end-modified poly (ß-aminoester) (OM-PBAE) are frequently used to ensure safety, and formulations are produced as aqueous dispersions, the stability of the nanoformulations is usually compromised. In this context, freeze-drying has aroused as a promising storage alternative to obtain solid nanoformulations with enhanced stability over time. Lyophilization is a challenging step that usually produces aggregation. Although some studies already achieved freeze-dried PBAE nanoparticles, none of them detailed the parameters that are critical for the success of this process. Moreover, due to the specific composition of each formulation, the critical parameters for the correct freeze-drying process need to be adjusted for each polyplex developed. In this paper, we have studied the variables that have a direct influence on the manufacturing and lyophilization of OM-PBAE nanoparticles with the aim to develop a versatile and robust freeze-drying receipt that properly preserves the library of polyplexes designed in our group, which have different pKa depending on the modification applied.

Efeitos da acupuntura nos acupontos Shenmen (C-7) e Neiguan (PC-6) sobre a frequência cardíaca, a variabilidade da frequência cardíaca e o ritmo cardíaco em cães saudáveis / Effects of acupuncture at Shenmen (C-7) and Neiguan (PC-6) acupoints on the heart hate, heart rate variability and cardiac rhythm in healthy dogs

Acupuncture derives from traditional Chinese medicine, which aims to restore homeostasis. The action mechanism of this technique involves stimulation of certain points on the skin by inserting a needle. The aim of this study was to evaluate the influence of stimulation of acupoints C7 and PC6 on the heart rate variability, heart rate and heart rhythm in healthy dogs. 30 male and female adult dogs were used, with no breed restriction. The animals were analyzed at two different times in weekly intervals. Firstly were applied needles in the true acupoints, and on the second time we applied needles in false acupoints. Previously to the acupuncture an ECG with 2 minutes of recorder was performed, and after an insertion of needles the electrocardiographic recording was maintained during the 30 minutes of acupuncture. Results showed no significant difference between the HR when comparing true and false acupoints (p = 0.890). For heart rate variability a small difference was observed between the groups (p = 0.0051), however, when comparing the baseline with 15 and 25 minutes of monitoring in the false acupoint group, no significant results were found when compared with true acupoint. In conclusion, it is suggested that the stimulation of acupoints C-7 and PC-6 in healthy dogs does not promote change in sympathovagal balance, specifically on the heart rate variability, heart rate and heart rhythm on healthy dogs.(AU)

Estudo comparativo da eletrocardiografia convencional e computadorizada em equinos das raças Quarto de Milha e Mangalarga Marchador / Comparative study of computerized and conventional electrocardiography in Quarter Horse and Mangalarga Marchador

A eletrocardiografia computadorizada é mais precisa e prática quando comparada à convencional e por essa razão vem ganhando espaço na rotina clínica. No entanto os valores de referência devem diferir para os dois métodos. O objetivo desse trabalho foi analisar e comparar o exame eletrocardiográfico computadorizado com o exame obtido pelo método convencional em equinos. O estudo demonstrou diferenças na amplitude da onda P (P<0,0001) com valor médio de 0,21 mV para o método convencional e 0,17 mV para o computadorizado; duração do intervalo PR (p=0,0005), tendo o valor médio de 260,49 ms para o método convencional e 242,37 ms para o informatizado e duração do complexo QRS (p=0,0003), sendo a média de valores para o método convencional de 75,61ms e 84,83 ms para o computadorizado. Essas diferenças devem ser levadas em consideração com o intuito de evitar equívocos na interpretação da eletrocardiografia na espécie equina.

Computerized electrocardiography has been gaining space in clinic routines because it is more practical and precise when compared to the conventional method. However, their reference values may differ from each other. The aim of this paper was to analyze and compare computerized and conventional electrocardiography in horses. Differences were observed between P wave amplitude (P<0001) with a mean of 0.21mV in the conventional method and 0.17mV in the computerized method, PR interval duration (p=0.0005) with a mean of 260.49 ms and 242.37 ms in the conventional and computerized methods respectively, and QRS complex duration (p=0.0003) with a mean of 75.61 ms in the conventional method and 84.83 ms in the computerized method. These differences should be taken into consideration in order to avoid misunderstandings in the interpretation of the electrocardiogram in equine species.

Small Bowel Obstruction due to Intestinal Xanthomatosis.

Vast majority of bowel obstruction is due to postoperative adhesions, malignancy, intestinal inflammatory disease, and hernias; however, knowledge of other uncommon causes is critical to establish a prompt treatment and decrease mortality. Xanthomatosis is produced by accumulation of cholesterol-rich foamy macrophages. Intestinal xanthomatosis is an uncommon nonneoplastic lesion that may cause small bowel obstruction and several cases have been reported in the English literature as obstruction in the jejunum. We report a case of small intestinal xanthomatosis occurring in a 51-year-old female who presented with one day of copious vomiting and intermittent abdominal pain. Radiologic images revealed jejunal loop thickening and inflammatory changes suggestive of foreign body obstruction, diagnostic laparoscopy found two strictures at the jejunum, and a pathologic examination confirmed a segmental small bowel xanthomatosis. This case illustrates that obstruction even without predisposing factors such as hyperlipidemia or lymphoproliferative disorders.

Home enteral nutrition in Spain; NADYA registry 2011-2012.

OBJECTIVE: To describe the results of the home enteral nutrition (HEN) registry of the NADYA-SENPE group in 2011 and 2012. MATERIAL AND METHODS: We retrieved the data of the patients recorded from January 1st 2011 to December 31st 2012. RESULTS: There were 3021 patients in the registry during the period from 29 hospitals, which gives 65.39 per million inhabitants. 97.95% were adults, 51.4% male. Mean age was 67.64 ± 19.1, median age was 72 years for adults and 7 months for children. Median duration with HEN was 351 days and for 97.5% was their first event with HEN. Most patients had HEN because of neurological disease (57.8%). Access route was nasogastric tube for 43.5% and gastrostomy for 33.5%. Most patients had limited activity level and, concerning autonomy, 54.8% needed total help. Nutritional formula was supplied from chemist's office to 73.8% of patients and disposables, when necessary, was supplied from hospitals to 53.8% of patients. HEN was finished for 1,031 patients (34.1%) during the period of study, 56.6% due to decease and 22.2% due to recovery of oral intake. CONCLUSIONS: Data from NADYA-SENPE registry must be explained cautiously because it is a non-compulsory registry. In spite of the change in the methodology of the registry in 2010, tendencies regarding HEN have been maintained, other than oral route.

Objetivos: Describir los resultados del registro de nutrición enteral domiciliaria (NED) del grupo NADYASENPE de los años 2011 y 12. Material y métodos: Se recopilaron los datos introducidos en el registro desde el 1 de enero de 2011 al 31 de diciembre de 2012. Resultados: Hubo 3021 pacientes en el registro durante el periodo, procedentes de 29 hospitales, lo que da una prevalencia de 65,39 casos por millón de habitantes. 97.95% fueron adultos, 51,4% varones. La edad media fue 67,64 ± 19,1 años y la mediana 72 años para los adultos y 7 meses para los niños. La duración media de la NED fue 351 días y para el 97,5% fue el primer episodio con NED. La mayoría de pacientes tenían NED por una enfermedad neurológica (57,8%). La vía de acceso fue sonda nasogástrica para el 43,5% y gastrostomía para el 33,5%. La mayoría de pacientes tuvieron un nivel de actividad física limitado y, respecto a la autonomía, 54,8% necesitaba ayuda total. La fórmula de nutrición se suministró desde las oficinas de farmacia para el 73,8% y los fungibles, cuando fueron necesarios, desde los hospitales para el 53,8%. La NED se suspendió en 1.031 pacientes (34,1%) durante el periodo de estudio, 56,6% debido a fallecimiento y 22,2% debido a recuperación de la vía oral. Conclusiones: Los datos del registro NADYA-SENPE deben ser interpretados con precaución ya que se trata de un registro voluntario. A pesar del cambio de metodología del registro en 2010, las tendencias en NED se han mantenido, salvo la importancia cuantitativa de la vía oral.

[Home parenteral nutrition in Spain 2011 and 2012; a report of the home and ambulatory artificial nutrition group NADYA]. / Nutrición Parenteral Domiciliaria en España 2011 y 2012: informe del grupo de nutrición artificial domiciliaria y ambulatoria NADYA.

OBJECTIVE: To report the data of the Home Parenteral Nutrition (HPN) registry of the NADYA-SENPE working group for the years 2011 and 2012. METHODOLOGY: We compiled the data from the on-line registry introduced by reviewers of NADYA group responsible for monitoring of NPD introduced by since January 1, 2011 to december 31, 2012. Included fields were: age, sex, diagnosis and reason for HPN, access path, complications, beginning and end dates, complementary oral or enteral nutrition, activity level, autonomy degree, product and fungible material supply, withdrawal reason and intestinal transplant indication. RESULTS: Year 2010: 184 patients from 29 hospitals , representing a rate of 3.98 patients/million inhabitants/ year 2011, with 186 episodes were recorded NPD . During 2012, 203 patients from 29 hospitals , representing a rate of 4.39 patients/million inhabitants/year 2012 , a total of 211 episodes were recorded NPD . CONCLUSIONS: We observe an increase in registered patients with respect to previous years.Neoplasia remains as the main pathology since 2003. Although NADYA is consolidated registry and has been indispensable source of information relevant to the understanding of the progress of Home Artificial Nutrition in our country, there is ample room for improvement. Especially that refers to the registration of pediatric patients and the registration of complications.

Objetivo: Comunicar los datos del registro de Nutrición Parenteral Domiciliaria (NPD) del grupo de trabajo NADYA-SENPE de los años 2011 y 2012. Material y métodos: Recopilación de los datos del registro "on-line" introducidos por los colaboradores del grupo NADYA responsables del seguimiento de la NPD desde el 1 de enero de 2011 al 31 de diciembre de 2012 dividido por años naturales. Resultados: Año 2010: Se registraron 184 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 3,98 pacientes/millón habitantes/año 2011, con 186 episodios de NPD. Durante el año 2012 se registraron 203 pacientes, procedentes de 29 hospitales, lo que representa una tasa de 4,39 pacientes/millón habitantes/año 2012, con un total de 211 episodios de NPD. Conclusiones: Se observa un aumento progresivo de los pacientes registrados respecto a años anteriores. El principal grupo patológico sigue siendo oncológico ocupando el primer lugar desde 2003. Aunque el registro NADYA es un registro consolidado y ha sido y es fuente imprescindible de información relevante para el conocimiento de los avances de la Nutrición Artificial Domiciliaria en nuestro país, queda un amplio margen para la mejora. En especial lo que hace referencia al registro de pacientes pediátricos y al registro de las complicaciones.

[Home parenteral nutrition registry in Spain for the year 2010: NADYA-SENPE Group]. / Registro del año 2010 de nutrición parenteral domiciliaria en España: Grupo NADYA-SENPE.

OBJECTIVES: To report the Group Registry NADYASENPE data about home parenteral nutrition (HPN) in Spain in 2010. MATERIAL AND METHODS: A descriptive study of the database of the national registry of HPN of NADYA-SENPE (December 10, 2009 to December 10, 2010). For the calculation of prevalence the latest data published by the Institute National Statistics Office (01/01/2009) was used. RESULTS: There were registered 148 patients from 23 hospitals, 86 women (58.11%) and 9 children (6.08%). The average age of the 139 patients older than 14 years was 53.06 ± 15.41 years. The average duration of HPN was 316.97 days/patient. The most common diagnosis in those younger than 14 years was short bowel traumatic with 5 cases (55.55%) and in those older than 14 years, palliative care cancer with 29 cases (19.59%). The reason for the indication for HPN was short bowel syndrome in 74 cases (47%). The access via most frequently recorded was tunneled catheter in 36 cases (22.78%) followed by implanted port-catheters in 13 cases (8.23%) and other pathways in 3 cases (1.90%). There were 23 catheterrelated infections (82.14%) which represented 0.49 /1,000 days of PN, all of which occurred in cases older than 14 years. During the year 24 episodes of HPN ended, the most frequent cause was the transition to oral nutrition in 12 episodes (50%). It was reported that patients had a normal activity in 70 episodes of HPN (44.30%) with complete autonomy in 88 episodes (55.69%). Some patients 39 (24.68%) were potential candidates for intestinal transplantation. CONCLUSIONS: The number of registered patients is slightly lower than the previous year, although the number of participating hospitals is the same. The most frequent complication remains catheter-related infection but its incidence has decreased from previous years, presenting the lowest rate since the creation of the record. Differences in participation in the registry observed in the Autonomous Communities causes the development of implementation strategies. There is a gradual increase in day length of HPN over the years, which suggests the chronic treatments of some patients and obliges to study the existence of a possible confounding factor, in case there is an oversight of closing an episode. Therefore, it is necessary to update the registry with warning systems that facilitate periodic review of the patients and optimize the validity of registration.

[New tables on hand strength in the adult population from Teruel]. / Nuevas tablas de fuerza de la mano para población adulta de Teruel.

OBJECTIVE: To elaborate the predicted values of hand strength in the adult population from the health care area of Teruel. MATERIAL AND METHODS: The population residing in the health care area of Teruel, aged > or = 20 years, with no physical disability precluding the performance of the different tests and voluntarily willing to participate. The subjects are weighed and measured barefoot, naked chest, and the body mass index is calculated. The hand strength is measured by means of a dynamometer with extended arms, parallel to the body and without support. The determinations are performed for both hands with a rest lasting few seconds between them and recording the highest value for each hand. Tables are elaborated for both genders, by age decades, with the corresponding percentiles for values of the right hand, left hand, and average values for each hand. RESULTS: A total of 2,270 cases were valid; 1,113 men, 1,157 women, with mean age of 62 and 55 years, respectively. The strength is higher at the right hand than in the left one, for both men and women, with average value of 27.5 kg (3-57) in men and 16.7 (1-44) in women. The highest values are found between ages 20 and 40 years, decreasing by 8% per decade. We found a relationship between mean strength and body mass index (r = 0.179, p = 0.0003 in men and r = -0.095, p = 0.001 in women). CONCLUSIONS: We elaborated tables of predicted values that will allow assessing the nutritional status of our population from a functional perspective and detecting its deviation. Strength is progressively lost from 50 years and on. There is a relationship between hand strength and nutritional status assessed by body mass index.

Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argentine patients.

OBJECTIVE: To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease. METHODS: Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects. RESULTS: DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03]. CONCLUSION: These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.

[Obstructive sleep apnea syndrome in childhood]. / Síndrome de apnea obstructiva del sueño en la infancia.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common problem in children. It is characterized by a partial airway obstruction associated with hypoxemia and hypoventilation rather than complete airway obstruction. DEVELOPMENT: Adeno-tonsillar hypertrophy is the leading cause but there are other risk factors like craniofacial abnormalities. OSAS may lead to neurodevelopmental abnormalities, growth and cardiorespiratory failure. It differs significantly from adult OSAS in its clinical presentation, polysomnographic findings and management. In spite of the fact that the diagnosis is often made on a clinical basis, the definitive and differential one only can be made by polysomnography. CONCLUSION: An overview of this pathology and the different polysomnographic parameters used are reported. Efforts to detect sleep apnea syndrome should be employed in children who present with the symptoms discussed. New guidelines for pediatric polysomnography should help standardize methods.

Pathological mineralizations: calcifications and Si-bearing particles in soft tissues and their eventual relationship to different prostheses.

Polarizing microscopy (PM), scanning electron microscopy (SEM), x-ray dispersive analysis (EDAX), x-ray diffraction (XRD), and infrared spectrometry (IR) were used to study the following pathological mineralizations: calcifications and silicon(Si)-bearing mineralizations in cerebral tissue from an epileptic child; traces of Si-bearing particles in periprosthesic mammarian tissue, and calcifications in capsular mammarian tissue from a patient with a silicone gel mammarian implant, and 2 calcium-bearing compounds, a typical apatitic calcification, and a nonphosphorous-bearing calcification in arterial tissues. In this tissue we also found Si-bearing particles due to an artifact from glassware.

The effect of melatonin in patients with fibromyalgia: a pilot study.

The aim of the study was to determine the possible effect of melatonin treatment on disturbed sleep, fatigue and pain symptoms observed in fibromyalgia (FM) patients. Twenty-one consecutive patients with FM were included in an open 4-week-duration pilot study. Before and after treatment with melatonin 3 mg at bedtime, patients were evaluated using tender point count by palpation of 18 classic anatomical regions, pain score in four predesignated areas, pain severity on a 10 cm visual analogue scale (VAS), sleep disturbances, fatigue, depression, anxiety, and patient and physician global assessments, also by a VAS. Urine 6-sulphatoxymelatonin levels (aMT-6S) were measured in the patients and 20 age- and sex-matched controls. Nineteen patients completed the study. One patient withdrew because of migraine and another was lost to follow-up. At day 30, median values for the tender point count and severity of pain at selected points, patient and physician global assessments and VAS for sleep significantly improved with melatonin treatment. Other variables improved but did not reach statistical significance. Adverse events were mild and transient. Lower levels of aMT-6S were found in FM patients compared with normal median controls (+/-SD, 9.16 +/- 7.9 microg/24 h vs 16.8 +/- 12.8 microg/24 h) (p = 0.06). Although this is an open study, our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM. Double-blind placebo controlled studies are needed.

A comparative study on the efficacy of the new quinolone alatrofloxacin in the treatment of experimental legionellosis in guinea pigs.

The in vivo efficacy of trovafloxacin, intraperitoneally administered as alatrofloxacin (CP-116,517), was assessed and compared with that of erythromycin, alone or in combination with rifampicin, in a model of Legionella pneumophila pneumonia in guinea pigs. Trovafloxacin (5 mg/kg administered as alatrofloxacin once daily for 7 days) gave a survival rate of 100% in infected animals. Clearance of bacteria and of bacteria-induced lesions from lungs was achieved by day 6 post-inoculation. The lungs of trovafloxacin-treated animals remained free of bacteria at day 28 post-challenge. Trovafloxacin proved as effective as erythromycin administered intraperitoneally, but was superior to erythromycin alone. or in combination with rifampicin, when given orally.

Antimicrobial susceptibility of Streptococcus pneumoniae isolated from pediatric carriers in Spain.

The in vitro activity of several beta-lactam agents, macrolides, and cotrimoxazole was investigated against 53 Streptococcus pneumoniae isolates recovered from healthy children. The rates of resistance to penicillin or amoxicillin, cefaclor, and cefuroxime were 30%, 51%, and 37%, respectively. No cefotaxime-resistant isolates were found. Rates of resistance to erythromycin, clarithromycin, and cotrimoxazole were 22.6%, 13.2%, and 83%, respectively. Pneumococci with divergent antimicrobial susceptibility profiles (susceptible or moderately resistant vs. resistant isolates) coexisted in 32% samples, with divergencies more often involving beta-lactam agents and/or macrolides. In five of these samples, isolates belonged to different serotypes.

Jaccoud's arthropathy of the hands in overlap syndrome.

The objective of this work was to evaluate the frequency and features of Jaccoud's syndrome of the hands in patients with overlap syndrome. Twenty-three patients with overlap syndrome were prospectively evaluated by means of a complete physical examination, serological assessment, and hand X-rays. The presence of Jaccoud's syndrome was defined by Kahn's criteria. Patients with or without Jaccoud's arthropathy were compared in their clinical, serological and radiological features. Five out of 23 patients (21.7%) presented Jaccoud's syndrome. Clinical and serological features of patients with or without the syndrome proved similar except for alignment abnormalities, which by definition were more frequent in the group with Jaccoud. A significantly greater number of patients meeting diagnostic criteria for SLE were observed in the Jaccoud group (80% versus 21%; p = 0.03). There was no other disease or associated condition such as chronic renal failure or high-dose steroid treatment concomitant with the development of Jaccoud's syndrome. It may be concluded that in patients with overlap syndrome, Jaccoud' arthropathy seems to be more frequent in patients who meet criteria for SLE.

[Activity of erythromycin and clarithromicin against isolates of Streptococcus pneumoniae with decreased sensitivity to penicillin obtained from healty carriers. Spanish Collaborative Group]. / Actividad de eritromicina y claritromicina frente a aislados de Streptococcus pneumoniae con sensibilidad disminuida a la penicilina obtenidos de portadores sanos. Grupo Colaborador Español.

BACKGROUND: Empirical treatment of pneumococcal upper and lower respiratory infections must be chosen on the basis of the susceptibility patterns of nasopharyngeal colonizing strains isolated from healthy carriers. METHODS: The susceptibility to erythromycin and clarithromycin was investigated by a conventional microdilution method among 103 pneumococci isolates recovered from healthy children (n = 63) and adults (n = 40) exhibiting decreased susceptibility to penicillin (MIC > or = 0.12 mg/l). RESULTS: 63% of penicillin -resistant pediatric isolates were susceptible to erythromycin and 78.9% were susceptible to clarithromycin . Among isolates with diminished susceptibility to penicillin , 77.7% were susceptible to erythromycin and 86.3% to clarithromycin . 90% of adult isolates were susceptible to erythromycin and to clarithromycin . Overall, clarithromycin exhibited a better activity than erythromycin . CONCLUSIONS: Clarithromycin , and to a lesser extent erythromycin , are good alternatives to penicillin in the empirical treatment of respiratory tract infections caused by pneumococci with diminished susceptibility to penicillin .

Linear scleroderma and melorheostosis: case presentation and literature review.

The case of a 9 year-old male patient with linear scleroderma and melorheostosis of the iliac bone is described. Radiological findings suggestive of osteopoikilosis were found in carpal and tarsal bones. A review of the literature on this unusual disease association is made.