Current Issues on Immunotherapy in Children

Therapy of allergic diseases in children implicates avoidance of allergens, standard pharmacotherapy, and immunotherapy. Immunotherapy is the only treatment for allergic diseases with the ability to change the natural course of the disease, thus stopping its further progression as well as the development of new allergic diseases and new sensibilizations. The objective of this chapter is to give insight into the latest data on immunotherapy in treating children with allergic diseases. Methods: The study involved a search for relevant articles on the MEDLINE and PubMed up to 2017. Results: Numerous studies have shown that the sublingual application of allergen-specific immunotherapy is adequate, safe, and efficient in the therapy of immunoglobulin E (IgE)-mediated allergic diseases of the respiratory tract in children, but there are still some questions to be solved concerning the usage of SLIT in children younger than 5 years old, SLIT for polysensitized patients, duration of SLIT, long-lasting effects of SLIT. Conclusions: In order to improve the clinical efficacy of SLIT, we are looking for new routes of administration, new allergens, new protocols as well as combination of SLIT with other immune modulatory treatments

Optimization of drug release from compressed multi unit particle system (MUPS) using generalized regression neural network (GRNN)

The purpose of this study was development of diclofenac sodium extended release compressed matrix pellets and optimization using Generalized Regression Neural Network (GRNN). According to Central Composite Design (CCD), ten formulations of diclofenac sodium matrix tablets were prepared. Extended release of diclofenac sodium was acomplished using Carbopol(R) 71G as matrix substance. The process of direct pelletisation and subsequently compression of the pellets into MUPS tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve more control of the process factors over the principal response - the release of the drug. The investigated factors were X(1) -the percentage of polymer Carbopol(R) 71 G and X(2)- crushing strength of the MUPS tablet. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 hour to 8 hours of dissolution. The most important impact on the drug release has factor X(1) -the percentage of polymer Carbopol(R) 71 G. The purpose of the applied GRNN was to model the effects of these two causal factors on the in vitro release profile of the diclofenac sodium from compressed matrix pellets. The aim of the study was to optimize drug release in manner wich enables following in vitro release of diclofenac sodium during 8 hours in phosphate buffer: 1 h: 15-40%, 2 h: 25-60%, 4 h: 35-75%, 8 h: <70%

In Vitro–In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation

The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented in GastroPlusTM software package. A range of experimentally determined, in silico predicted or literature data were used as input parameters. Experimentally determined pH-solubility profile was used for all simulations. The human jejunum effective permeability (Peff) value was estimated on the basis of in vitro measured Caco-2 permeability (literature data). The required PK inputs were taken from the literature. The results of the simulations were compared with actual clinical data and revealed that the GIST-model gave accurate prediction of gliclazide oral absorption. The generated absorption model provided the target in vivo dissolution profile for in vitro–in vivo correlation and identification of biorelevant dissolution specification for GLK immediate-release (IR) tablets. A set of virtual in vitro data was used for correlation purposes. The obtained results suggest that dissolution specification of more than 85% GLK dissolved in 60 min may be considered as “biorelevant” dissolution acceptance criteria for GLK IR tablets

Evaluation of diclofenac sodium release from matrix pellets compressed into MUPS tablets

The purpose of the study was to screen the effects of formulation factors on the in vitro release profile of diclofenac sodium from matrix pellets compressed into multiple unit pellet system (MUPS) tablets using design of experiment (DOE). Extended release of diclofenac sodium was accomplished using Carbopol 71G as matrix substance. According to Fractional Factorial Design FFD 2(3-1) four formulations of diclofenac sodium MUPS matrix tablets were prepared. The process of direct pelletization and subsequently compression of the pellets into tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve a better control of the process factors over the principal response - the release of the drug. The investigated factors were X1-the percentage of polymer Carbopol 71G, X2-crushing strength of the tablet and X3-different batches of the diclofenac sodium. In vitro dissolution time profiles at 6 different sampling times were chosen as responses. Results of drug release studies indicated that drug release rates vary between different formulations, with a range of 1 to 8 h to complete dissolution. The most important impact on the drug release had factor X1-the percentage of polymer Carbopol 71G. The polymer percentage is suggested as release regulator for diclofenac sodium release from MUPS matrix tablets. All other investigated factors had no significant influence on the release profile of diclofenac sodium

Capgras syndrome as part of delusional organic disorder

Capgras syndrome is a substantial disorder of thought which is characterized by wrong identification of close persons (mistaken identity), i.e. resolute conviction that there is a double, a cheater, in the form of a familiar person. This paper presents an 81-year-old female patient, with an oppositional attitude, occasional psychomotor agitation, verbally aggressive towards the double and the children because they have replaced her husband. She verbalized suicidal intentions and tendencies because she could not stand living with a stranger. Uncertain temporal-spatial orientation, distraction of attention, cognitive deficit, dystrophy, labile affect and global reduction of dynamism were recorded as associated symptoms. The patient and her family refused hospitalization because the ambulatory diagnostic procedures were conducted (CT scan of the head, psychological screening tests and laboratory analyses) and pharmacotherapy was introduced (risperidone, lorazepam), with check-ups in five-day intervals. Within the application of therapy, there was a correction in the identification of the husband, with occasional, short-term ambivalence and the consequent reduction of anxiety, but with persistent spatiotemporal disorientation, distraction of attention and memory deficit. The introduction of drugs for the treatment of dementia was considered, too. Hetero-anamnestic data, neurological and psychiatric status indicated that this patient suffered from a delusion of mistaken identity due to a complex psycho-organic syndrome. Further research of this disease is needed in order to obtain more effective treatment strategies and more complete knowledge of neuropsychological models of facial recognition

Porotic paradox: distribution of cortical bone pore sizes at nano- and micro-levels in healthy vs. fragile human bone

Bone is a remarkable biological nanocomposite material showing peculiar hierarchical organization from smaller (nano, micro) to larger (macro) length scales. Increased material porosity is considered as the main feature of fragile bone at larger length-scales. However, there is a shortage of quantitative information on bone porosity at smaller length-scales, as well as on the distribution of pore sizes in healthy vs. fragile bone. Therefore, here we investigated how healthy and fragile bones differ in pore volume and pore size distribution patterns, considering a wide range of mostly neglected pore sizes from nano to micron-length scales (7.5 to 15000 nm). Cortical bone specimens from four young healthy women (age: 35 +/- 6 years) and five women with bone fracture (age: 82 +/- 5 years) were analyzed by mercury porosimetry. Our findings showed that, surprisingly, fragile bone demonstrated lower pore volume at the measured scales. Furtnermore, pore size distribution showed differential patterns between healthy and fragile bones, where healthy bone showed especially high proportion of pores between 200 and 15000 nm. Therefore, although fragile bones are known for increased porosity at macroscopic level and level of tens or hundreds of microns as firmly established in the literature, our study with a unique assessment range of nano-to micron-sized pores reveal that osteoporosis does not imply increased porosity at all length scales. Our thorough assessment of bone porosity reveals a specific distribution of porosities at smaller length-scales and contributes to proper understanding of bone structure which is important for designing new biomimetic bone substitute materials. [GRAPHICS