Cross-linked hyaluronic acid sub-micron particles: in vitro and in vivo biodistribution study in cancer xenograft model.

This paper focused on the biodistribution of the cross-linked hyaluronic acid (HA-NPs) sub-micron particles in tumor-bearing mice. Solvent-non solvent method followed glutaraldehyde cross-linking utilized for the fabrication of HA-NPs. Size measurement and morphological analysis were performed by dynamic light scattering and electron microscopy, respectively and the size found to be in the range of 200-400 nm. In vitro viability in LNCaP cell line was assessed by water soluble tetrazolium assay after 24 h of exposure to sub-micron particles and no toxicity was found to higher concentration of 3 mg/mL. Internalization of particles in prostate cancer cell LNCaP were studied by confocal microscopy with FITC labeled submicron particles and involvement of hyaluronan receptor mediated uptake/endocytosis was confirmed by competitive assay. Biodistribution studies were performed in xenograft prostate cancer mice model with fluorophore labeled particles and monitored in tumoral parenchyma with strong fluorescence, meanwhile very less signal in liver, kidney and spleen while no fluorescence found in lung after 24 h of systemic administration; that shown ability of this HA based system to recognize cancer tissue. These result fetched that hyaluronic acid based system is selective for tumoral site and can be utilized to deliver bioactives in specific (targeting) and controlled (temporal) manner to cancerous tissue.

Effective production of a thermostable alpha-glucosidase from Sulfolobus solfataricus in Escherichia coli exploiting a microfiltration bioreactor.

A microfiltration (MF) membrane bioreactor was developed for an efficient production of a recombinant thermostable alpha-glucosidase (rSsGA) from Sulfolobus solfataricus MT-4. The aim of the membrane bioreactor was to improve the control of the concentration of key components in the growth of genetic engineered microorganisms, such as Escherichia coli. The influence of medium composition was studied in relation to cell growth and alpha-glucosidase production. The addition of components such as yeast extract and tryptone resulted in a higher enzyme production. High cell density cultivation of E. coli BL21(DE3) on semidefined medium, exploiting a microfiltration bioreactor, was studied in order to optimize rSsGA production. In addition to medium composition, the inducer employed (either isopropyl beta-D-thiogalactopyranoside or lactose), the induction duration, and the cultivation mode influenced both the final biomass and the enzyme yield. The MF bioreactor allowed a cell concentration of 50 g/L dry weight and a corresponding alpha-glucosidase production of 11,500 U/L. The improvement obtained in the enzyme production combining genetic engineering and the microfiltration strategy was estimated to be 2,000-fold the wild-type strain.

Patellofemoral malalignment in adolescents. Computerized tomographic assessment with or without quadriceps contraction.

Twenty-seven adolescents with anterior knee pain with or without patellar instability were studied by computerized tomography to detect patellofemoral malalignment. The examination was performed with and without quadriceps contraction with the knee flexed to 15 degrees. Congruence angle, patellar tilt angle, sulcus angle, and trochlear depth were measured. This investigation showed the well-known types of patellofemoral malalignment with quadriceps relaxed (tilted, lateralized, lateralized, and titled patella) and, in 52% of cases, revealed changes in type and severity with quadriceps contraction (in 41%, lateralization and tilting were markedly more evident; in 11%, the type of malalignment changed). The results demonstrate that, in addition to assessment with quadriceps relaxed, computerized tomography with quadriceps contraction is a useful adjunct to diagnose and define the type of malalignment in particularly difficult circumstances.

[The indications for and limits of "extensive" posterior lysis in the surgical treatment of congenital clubfoot (talipes equinovarus supinatus)]. / Indicazioni e limiti della lisi posteriore "allargata" nel trattamento chirurgico del piede torto congenito equino-varo-supinato.

The authors present the preliminary results (after 4-7 years) of 69 cases of congenital torsive equino-varus-supinated foot treated operatively from 1982 to 1985 (of a total of 25% cases treated from 1982 to 1989). Both the modalities and the stages of execution of the treatment are described. After the initial clinical evaluation and the first weeks of manipulation, the feet were immobilized in corrective plaster casts, which were carefully constructed to correct the varus and supination. After 4-8 months, thorough clinical and radiographic assessment enabled the authors to plan the surgical procedure for correction of the remaining deformity, customizing it for each individual patient. There is an in-depth discussion of the stages of the "widened" posterior release procedure. Using this procedure, the authors achieved satisfactory intraoperative correction in 85% of the patients, correction which was maintained over time in 76.5% of the cases. In this way the medial stage of the surgical procedure, associated "ab initio" to the posterior release, may be reserved to a fewer number of patients (15-20%) under one year of age.

[Metaphyseal and diaphyseal fractures of the femur resulting in growth inequality in children under 3 years of age]. / L'esito in dismetria delle fratture metafisarie e diafisarie del femore in bambini fino ai 3 anni di età.

The authors clinically and radiographically review 42 of 53 children between the ages of 5 months and 3 years treated by closed means from 1983 to 1987 for femoral fracture (average follow-up, 4 years). Evaluation of a large number of patients in this particular age group offers several advantages: a) it regards a phase of evolution in which the modalities of growth do not affect in any significant way the metabolic balance of the growth plate chondrocyte, as occurs in periods of rapid growth. This makes the sample group statistically homogeneous; b) it eliminates the age variable in the search for the factors which may contribute to limb-length discrepancy. The importance of the following factors was statistically analyzed: location, type, and initial displacement of the fracture, accuracy of reduction, and characteristics of the traumatic event. There was a significant correlation between a large degree of limb lengthening and further reduction or corrective procedures under general anesthesia. Overlapping reduction and limb shortening were also closely related. A highly significant correlation was also found between limb lengthening exceeding 15 mm. (range, 15-22 mm.) and the time of day at which the trauma occurred (9-10 pm). The results of treatment suggest the need for a reevaluation, using recently gained knowledge, of Lacroix's theory of the pathogenesis of this disorder as well as the need to examine more thoroughly, with further clinical and experimental studies, the hormonal changes following the trauma.

[Surgical treatment of diaphyseal fractures of the forearm during pre-adolescent age]. / Il trattamento chirurgico delle fratture diafisarie dell'avambraccio in età evolutiva.

The results of treatment of 10 both-bone unstable diaphyseal fractures of the forearm in children by open-reduction and intramedullary fixation with Kirschner wiring of the radius are presented. All fractured healed in perfect alignment. No complications occurred. In a 3 year and 2 month follow-up all the patients had excellent results with full range of movement. The advantages of this method are: a) it is easy to carry out; b) it maintains anatomical reduction; c) a second operation to remove the internal fixation device is not required; d) fixation of the ulna is not necessary, because in all patients a realignment of the ulnar fragments occurred after radius reduction.

[Rare skeletal pathology: the diagnostic problems in the first year of life]. / Patologia rara dello scheletro: problemi diagnostici nel primo anno di vita.

The authors report a series of affections which determine diffused modifications of the skeleton during early childhood. More common pathological forms are dealt with, of relatively simple diagnosis, and having pathological pictures which based on frequency, means of occurrence, and clinical-radiographic aspects, are rarely observed, and difficult to diagnose. Based on several clinical cases, the authors report problems related to diagnosis, emphasising the meaning of various radiographic pictures and the value and choice of hematochemical tests aimed at selecting patients in whom biopsy is required.

[Torsional changes in the lower limbs in childhood]. / Le alterazioni della torsione degli arti inferiori in età pediatrica.

Based on their observation of approximately 1000 patients aged from 4 to 14 years and on a comparison of their experience with the data reported in the literature, the authors discuss the problem of modifications in torsion of the lower limbs during pediatric age. After a brief discussion of anatomy and the natural progression of the angle of femoral anteversion and tibial torsion, they stop to accurately describe the most frequently occurring defects in torsion, both isolated and combined. After affirming the contribution that axial vision has made to an understanding of the subject, they emphasise the current usefulness of the method in cases in which a clinical examination allows for doubts to persist and, in particular, if qualitative and quantitative diagnosis is required in relation to the therapeutic protocol. The authors conclude by suggesting that therapy be carried out during the growth age (much before 14 years of age) while they suggest waiting until skeletal maturity in order to make a general evaluation and to decide on treatment of combined defects.

[Congenital metatarsus varus]. / Il metatarso varo congenito.

The authors report on "congenital primitive metatarsus varus". After discussing the incidence, etiology, pathogenesis and classification, the clinical features and associated malformations are evaluated. Then they go into treatment details affirming, according to the literature, that this malformation is susceptible to complete regression if treated bloodlessly during the early months of life, and in any case, before the onset of loss of ambulation, by manipulations followed by a series of plaster casts and finally by corrective braces and shoes. If this treatment is fruitless or in cases seen at an advanced age and with a high degree of varus, there are several surgical operations that achieve satisfying results operating on tendons or on articular capsules.

[Congenital hallux valgus]. / Alluce varo congenito.

Congenital hallux varus is a rare deformity. The authors discuss 3 clinical cases observed and define the specific features of the anomaly. The clinical and radiographic pictures are described, emphasising essential aspects and possible variations, including the rare occurrence of congenital varus of a single interphalangeal joint. Differential diagnosis is discussed and surgical indications determined.