Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression. DESIGN: Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury. RESULTS: HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28). CONCLUSIONS: These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.

Gemelos monocigóticos con rabdomiomas cardiacos asociados a esclerosis tuberosa materna / Monozygotic twins with cardiac rhabdomyomas associated with maternal tuberous sclerosis

La esclerosis tuberosa es una enfermedad autosómica dominante que afecta cualquier órgano. Se presenta el caso de una paciente femenina de 23 años con diagnóstico de un año de evolución de esclerosis tuberosa por presencia de lesiones dermatológicas en cara, con embarazo gemelar monocorial biamniótico en donde ambos fetos cursan con rabdomiomas cardiacos. Actualmente en seguimiento con ecocardiografía fetal, por lo que se discute el control prenatal, así como los riesgos posnatales de ambos fetos. La importancia de esta revisión radica en el asesoramiento genético de la paciente y el abordaje multidisciplinario.(AU)

Tuberous sclerosis is an autosomal dominant disease affecting any organ. The case is presented on a 23 year-old patient with a diagnosis of tuberous sclerosis of 1 year onset with Monochorionic diamniotic twin pregnancy in which both foetuses had cardiac rhabdomyomas. The patient is currently on follow-up with foetal cardiac ultrasound. A discussion is presented on the prenatal monitoring, as well as postnatal risks of both foetuses. The importance of this review lies in the genetic counselling of the patient and the multidisciplinary approach.(AU)

Effect of the Melicoccus bijugatus leaf and fruit extracts and acidic solvents on the antimicrobial properties of chitosan-starch films.

AIM: Analysing the antimicrobial activity-against food-borne micro-organisms-of modified chitosan-starch films using formic and acetic acid as chitosan solvents and Melicoccus bijugatus leaves and fruit extracts. METHODS AND RESULTS: The films' antimicrobial activity against mesophilic aerobic bacteria, total coliform and fungi were also analysed, in accordance with the Mexican Official Norms (NOM-092-SSA1-1994, NOM-111-SSA1-1994 and NOM-113-SSA1-1994). The pH values of the films and extracts were measured, and the volatile compounds of the extracts and two films were determined by Gas Chromatography-Mass Spectrometry (GC-MS) considering the relationship among the type of compounds, extracts concentration, films' pH and the antimicrobial activity against bacteria and fungi. The best results are obtained by films with formic acid and 10% (v/v) of leaf and fruit extracts, in comparison with untreated chitosan-starch films. CONCLUSIONS: The extracts' compounds improved the films' antimicrobial capacity and inhibited the growth of micro-organisms with no previous sterilization required. It is correlated to the pH of the media, the combination of solvent/extract used and its concentration. SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of the few researches where the antimicrobial activity of M. bijugatus extracts is studied. It was found that the presence of these extracts is capable of improving the antimicrobial activities of chitosan-starch films. The performance of the modified films suggests their potential application as novel food packaging materials and encourages further research.

Population kinetics of tobramycin in neonates.

The population kinetics of tobramycin were studied in 140 neonates (100/40 patients for the index/validation groups, respectively) of 30 to 42 weeks' gestational age and 0.8 to 4.25 kg current body weight in their first 2 weeks of life, undergoing routine therapeutic drug monitoring of their tobramycin serum levels. The 365 tobramycin concentration measurements obtained were analyzed by use of NONMEM according to a one-compartment open model with zero-order absorption and first-order elimination. The effect of a variety of demographic, developmental, and clinical factors (gender, height, birth weight, current weight, gestational age, postnatal age, postconceptional age, and serum creatinine concentration) on clearance and volume of distribution was investigated. Forward selection and backward elimination regression identified significant covariates. The final pharmacostatistical model with influential covariates was as follows (full population): clearance (L/h) = 0.0508 x current weight (kg), multiplied by 0.843 if birth weight was 2.5 kg or less (low-birthweight infants), and volume of distribution (L) = 0.533 x current weight (kg). Using the proportional error model for the random-effects parameters, interindividual variability for clearance and for volume of distribution was determined to be 25.8% and 21.9%, respectively, and the residual variability was 19.2%. In this study, the use of the NONMEM gave significant and consistent information on the pharmacokinetics and the determinants of the pharmacokinetic variability of tobramycin in neonates when compared with available bibliographic information. Moreover, the final population pharmacokinetic model may be used to design a priori recommendations for tobramycin and to improve the dosing readjustments through Bayesian estimation.

Nsc and Fmoc Nalpha-amino protection for solid-phase peptide synthesis: a parallel study.

The 2-(4-nitrophenylsulfonyl)ethoxycarbonyl (Nsc) group is an alternative to Fmoc for Nalpha-protection in solid-phase peptide synthesis. Nsc-amino acids may be particularly suitable for automatic synthesizers, in which the amino acids are stored in solution, and the incorporation of residues prone to racemization such as Cys and His. Owing to the hydrophilicity of the Nsc group, these derivatives are useful for the preparation of protected peptides in convergent solid-phase peptide synthesis strategies.

Pharmacokinetics of amikacin in intensive care unit patients.

OBJECTIVE: To characterize the population pharmacokinetics of amikacin in intensive care unit (ICU) patients and to analyse whether these patients show different kinetic behaviour on the basis of their clinical diagnoses. METHOD: The patient population comprised 104 medical ICU patients on amikacin treatment for several presumed or documented Gram-negative infections. Four study groups were defined according to patients' clinical diagnosis: sepsis group (n = 39), trauma group (n = 20), pneumonia group (n = 21) and 'other diagnosis' group (n = 24). The pharmacokinetic parameters for amikacin in these patients were then compared. RESULTS: The ICU patients were found to have increased values for the amikacin volume of distribution (0.52 +/- 0.21 litres/kg), whereas total amikacin clearance expressed as a linear function of creatinine clearance was Cl (ml/min/kg) = 0.13 +/- 0.86 ClCR, which is not significantly different from other estimations reported in the literature. However, this relationship revealed statistically significant differences among the four groups of ICU patients. Moreover, the septic and trauma patients showed higher (but not statistically significant) values for the amikacin volume of distribution. CONCLUSION: The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses.