Targeted therapies for glioblastoma treatment.

Glioblastoma, the most common and aggressive type of brain tumor in adults, poses significant challenges in terms of treatment. Conventional approaches including surgery, chemotherapy, and radiotherapy have yielded limited success, with a median survival of approximately 15 months. However, extensive research into the biology of glioblastoma has identified molecular targets that can be exploited by newly developed drugs, leading to the emergence of precise personalized therapies. Several innovative treatment strategies are currently under development, aiming to enhance effectiveness while minimizing side effects. Clinical trials are underway to evaluate the efficacy of monoclonal antibodies that target glioblastoma cells, either by blocking specific receptors or by modifying molecular interactions that impede cell proliferation. Another promising avenue involves the use of oncolytic viruses designed to selectively infect glioblastoma cells. Additionally, the review explores the utilization of nanocarriers capable of surmounting the formidable obstacle of the blood-brain barrier, enabling efficient drug delivery. Cell therapies represent another promising approach, with dendritic cells, chimeric antigen receptor-T cells, and macrophages emerging as potential treatment modalities. By summarizing recent advances in targeted therapies against glioblastoma, this review aims to provide a comprehensive overview of ongoing efforts to discover effective and safe methods for treating glioblastoma patients. The ultimate goal is to improve patient outcomes and transform the landscape of glioblastoma treatment.

Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

3D Computed Tomography vs. 2D radiography: comparison of 3D direct anthropometry with 2D norm calculations and analysis of differences in soft tissue measurements.

OBJECTIVE: The aim of this study was twofold: (1) to compare soft tissue measurements of the same distances obtained from 3D computed tomography reconstructions with 2D cephalometric radiograms, (2) to compare data from 3D measurements from direct anthropometry and 2D "norms" for the facial measurements. PATIENTS AND METHODS: A total of 40 Caucasian patients that had their CBCT scans for various dental and dentoskeletal reasons were enrolled in this study. All the patients had large field of view (from the forehead to the chin). The data were stored in DICOM format and imported into a software for 3D reconstructions. After 3D facial soft tissue model generation, the distances between 18 soft tissue points were measured. The 3D soft tissue analysis was performed, and the facial indices were calculated. The mean 3D values were compared with 2D measurements performed on lateral cephalograms and Arnett's and Farkas' norms. The measurements were statistically compared using Student's t-test. RESULTS: Assessments from 2D and 3D measurements showed no statistical difference except for the distance Pogonion (for both male and female) and Labial superius prominence (females) to the True Vertical Line in 2D /Plane in case of 3D measurements. There was a significant difference between all 3D measurements and Arnett's and anthropometric Farkas' "norms". The mean difference between Farkas' "norms" and 3D measurements was within 3 mm for 70% of measurements. CONCLUSIONS: According to the results, 3D soft tissue analysis allows for complete diagnostic determination. The 3D "norms" are to be verified on a greater sample.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Transition moment directions and selected spectroscopic properties of Ivabradine.

Based on the Kawski-Gryczynski method the value of angle ß=38° between absorption and fluorescence transition moments of Ivabradine was determined. Such a high value of ß is responsible for low emission anisotropy of Ivabradine in a rigid polyvinyl alcohol matrix and in anhydrous glycerol despite the elongated shape of the fluorophore. Selected steady-state and time-resolved spectroscopic results support the analysis.

The pig CART (cocaine- and amphetamine-regulated transcript) gene and association of its microsatellite polymorphism with production traits.

The cocaine- and amphetamine-regulated transcript (CART) gene is a candidate gene that may affect performance and body composition traits in the pig. The purpose of this study was to establish the chromosomal localization and genomic sequence of the porcine CART gene, search for polymorphism and analyse its phenotypic effect in 644 pigs representing two breeds, Polish Large White (PLW) and Polish Landrace (PL), and a synthetic line 990 (L990). The CART gene was fluorescence in situ hybridization (FISH)-mapped to the chromosome 16q21. The 1878 bp DNA fragment covering three exons, two introns and the 5' flanking region was sequenced and analysed. A new A/G single nucleotide polymorphism (SNP) at position -238 bp was found. The coding sequence was conserved between porcine and human CART genes. Previously unknown short tandem repeat polymorphism (CA)(2)(CG)(n)(CA)(n) was identified in intron 2. Three alleles 251, 253 and 259 bp were found. The 251-bp allele was predominant in all the analysed populations of pigs, whereas the 253-bp allele occurred with the lowest frequency. The statistical analysis revealed significant allelic additive effects on meat content in carcass (p < 0.05) and abdominal fat weight (p < 0.01) in PLW, and meat content in carcass (p < 0.05) and backfat thickness (p < 0.05) in PL. Our study confirmed that chromosome region harbouring the CART gene is a promising quantitative trait loci for pig production traits.

Campylobacter spp. in waters of three main western Pomerania water bodies.

Campylobacters are responsible for increasing numbers of gastroenteritis cases in humans as well as miscarriages and diarrhea in farm and domestic animals. Surface waters are potential reservoirs and transmitting vehicles for these bacteria. Subject of analysis were surface water samples collected from the River Odra, Szczecin Lagoon and the Pomeranian Bay in monthly or bimonthly intervals, starting from April 1998. Analysis directed on campylobacters included enrichment in Preston broth prior to plating on CCDA isolation medium and identification, to the species level, by the api CAMPY tests. The detection level of the method was 1 CFU/10 ml. Numbers of total and faecal coliforms were counted according to the national standards. In addition water temperature and water saturation with oxygen were measured. Presence of Campylobacter spp., at the level detectable by the method applied, was confirmed in 19.7% of the Odra River, 5.6% of the Szczecin Lagoon and 0% of the Pomeranian Bay surface water samples. The contamination level of the Campylobacter--positive surface water samples did not exceed 10 CFU/ml. Isolation frequency depended on water purity class, counts of total and faecal coliforms and sampling site (p < 0.01). Species dominating in the River Odra and Szczecin Lagoon surface waters were C. jejuni ssp. jejuni and C. coli, respectively.

Determination of piracetam in human plasma by capillary electrophoresis.

A capillary electrophoresis (CE) procedure has been developed for the determination of piracetam in human plasma. Analyses were performed on an uncoated silica capillary using borax buffer modified with the addition of alpha-cyclodextrin. The detection was UV, operated at 200 nm. The detection limit of the authentic samples was 1 microg/ml. The calibration curve was linear over a range of 4 to 24 microg/ml (r=0.997). Inter-assay R.S.D. was below 9.3%. The described method has been successfully applied to the quantitative determination of piracetam in human plasma and should be useful for clinical and bioavailability investigations.

Bone status after long-term anticonvulsant therapy in epileptic patients: evaluation using quantitative ultrasound of calcaneus and phalanges.

The bone status of 25 epileptic female patients on long-term (mean 19 y) anticonvulsant therapy was investigated using quantitative ultrasound of the calcaneus (Lunar Achilles) and phalanges (Igea DBM Sonic 1200). Comparisons were made with a control group of 43 normal healthy women. Radiogrammetric measurements of the second metacarpal bone were also made in the epileptic patients. While all of the ultrasonic parameters were reduced in the epileptic group, differences only achieved statistical significance for speed of sound (SOS) at the phalanges. Phalangeal SOS correlated significantly with cortical thickness of the second metacarpal bone (r = 0.44, p < 0.05). The data suggest that long-term anticonvulsant therapy is associated with significant cortical bone loss. Quantitative ultrasound may have a role in monitoring bone loss in epileptic patients and in guiding suitable preventive therapy.

[Long-term results of vitrectomy in children and adolescents]. / Odlegle wyniki witrektomii u dzieci i mlodziezy.

PURPOSE: Assessment of vitrectomy in the treatment of children and adolescents. MATERIAL AND METHODS: We evaluated the treatment of 44 children between the ages of 8 and 17 who underwent vitrectomy from January 1991 to January 1996. In 35 eyes indication for vitrectomy was complicated intraocular trauma, in 6 eyes Toxocara canis infection, in 2 eyes idiopathic vitreous hemorrhage and in eye complication due to diabetes. The mean follow-up period of study was 15 months. RESULTS: The anatomic success category included eyes with attached retinas and a final visual acuity above 1/50 which was achieved in 85% of operated eyes. Within this group 50% of the eyes had a final visual acuity of 5/50 or better. Anatomic and functional success were stable for a period of 12 months after vitrectomy. CONCLUSIONS: 1. Vitrectomy is the primary method of treatment for complicated intraocular trauma in children. 2. Through vitrectomy we achieved functional success which facilitated visual rehabilitation after ocular trauma. 3. Vitrectomy in children and adolescents have fewer complications when compared to vitrectomy in adults.

[Vitrectomy in Terson's Syndrome]. / Witrektomia w zespole Tersona.

AIM OF THE STUDY: The authors present results of vitrectomy in the treatment of a 50 year old woman with Terson's Syndrome. MATERIAL: Pars plana vitrectomy was performed in two eyes of a 50 year old woman with vitreous hemorrhage caused by the rupture of cerebral arteries aneurysms. The vitreous hemorrhage occurred two days after the neurosurgery procedure. Visual acuity in both eyes was hand movement and did not change after pharmacotherapy and cryotherapy. Pars plana vitrectomy was performed in the right eye 3, 5 months after the hemorrhage and in the left eye 5 months after the hemorrhage. Visual acuity 5/12 in the right eye and 5/7 in the left eye was achieved after the vitrectomy and 5/50 (the decrease caused by cataract) and 5/7 after 11 and 7 months of follow-up. CONCLUSION: Pars plana vitrectomy is a method of choice in the cases of binocular Terson's Syndrome and accelerates returning of useful visual acuity.

High-performance liquid chromatographic and capillary electrophoretic determination of free nicotinic acid in human plasma and separation of its metabolites by capillary electrophoresis.

Two methods are described based on high-performance liquid chromatography and capillary electrophoresis that provide the selective and sensitive determination of nicotinic acid in human plasma. Moreover, the capillary electrophoresis system was used for the separation of nicotinic acid, nicotinamide, nicotinamide N-oxide, N'-methylnicotinamide, 6-hydroxynicontinic acid, nicotinuric acid and barbital (internal standard). The extraction procedure is simple; no gradient elution or derivatization is required. Both methods can be useful for clinical and biomedical investigations.

Effect of temperature on separation of norgestrel enantiomers by high-performance liquid chromatography.

The influence of mobile phase composition, concentration of beta-cyclodextrin and temperature on the high-performance liquid chromatographic separation of norgestrel was studied. In studies of the effect of temperature on the enantioselectivity of (+/-)-norgestrel, acetonitrile-water (25:75, v/v) modified by the addition of beta-cyclodextrin (14 mM) was applied as the mobile phase. Enantiomers were detected using UV detection at 240 nm. The capacity factors were measured over a wide range of column temperatures from -5 to 70 degrees C.

Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-AZA-9a-homoerythromycin A derivatives; a new class of macrolide antibiotics, the azalides.

A series of erythromycin A-derived semisynthetic antibiotics, featuring incorporation of a basic nitrogen atom into a ring expanded (15-membered) macrocyclic lactone, have been prepared and biologically evaluated. Semisynthetic modifications focused upon (1) varied substitution at the macrocyclic ring nitrogen and (2) epimerization or amine substitution at the C-4'' hydroxyl site within the cladinose sugar. In general, the new azalides exhibit improved Gram-negative potency, expanding the spectrum of erythromycin A to fully include Haemophilus influenzae and Neisseria gonorrhoeae. When compared to erythromycin A, the azalides exhibit substantially increased half-life and area-under-the-curve values in all species studied. The overall in vitro/in vivo performance of N-methyl, C-4'' epimers 3a and 9; and C-4'' amine 11 identify these compounds as the most interesting erythromycin A-superior agents. Compound 3a has been advanced to clinical study.