Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy

Targeted drug delivery systems are one of the most promising alternatives for the cancer therapy. Rapid developments on nanomedicine facilitated the creation of novel nanotherapeutics by using different nanomaterials. Especially polymer based nanoparticles are convenient for this purpose. In this study; a natural polymer (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix for the production of a novel nanotherapeutic including antineoplastic agent, Etoposide and attached folic acid as a ligand on the nanoparticles. Modified solvent evaporation technique was used for the production of PHBHHX nanoparticles and the average size of the obtained PHBHHX nanoparticles were observed in the range of 180 nm and 1.5 μm by the change in experimental conditions (i.e., homogenization rate, surfactant concentration and polymer/solvent ratio). By the increase in homogenization rate and surfactant concentration, size of the nanoparticles was decreased, while the size was increased by the increase in polymer/solvent ratio. Drug loading ratio was also found to be highly affected by polymer/drug ratio. Surface charge of the prepared nanoparticles was also investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide loaded and folic acid attached PHBHHX nanoparticles were observed as more effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX nanoparticles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated nanoparticles has the ability to selectively target to cancer cells. In addition, apoptotic/necrotic activities were evaluated for all formulations of the PHBHHX nanoparticles and parallel results with cytotoxicity tests were obtained. These studies demonstrate that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as promising for the targeted cancer therapy.     

Enterocolic lymphocytic phlebitis: an unusual cause of abdominal complaints

Enterocolic lymphocytic phlebitis (ELP) is a rare disease of unknown etiology involving most often the intramural and mesenteric small and medium-sized veins of the gastrointestinal tract. The diagnosis of the disorder is based on the histopathological examination of a surgical specimen as endoscopically obtained diagnostic material is usually too superficial. Clinical manifestation of ELP most frequently is characterized by acute symptoms, such as acute abdomen, signs suggesting acute appendicitis, gastrointestinal hemorrhage, sometimes it manifests as chronic gastrointestinal complaints. We report, to our knowledge for the first time in Poland, a case of ELP with clinical symptoms pointing to acute appendicitis, on laparoscopy manifesting as a tumorous mass in the colonic wall with an unchanged appendix.     

The mismatch negativity (MMN)--a unique window to disturbed central auditory processing in ageing and different clinical conditions

In this article, we review clinical research using the mismatch negativity (MMN), a change-detection response of the brain elicited even in the absence of attention or behavioural task. In these studies, the MMN was usually elicited by employing occasional frequency, duration or speech-sound changes in repetitive background stimulation while the patient was reading or watching videos. It was found that in a large number of different neuropsychiatric, neurological and neurodevelopmental disorders, as well as in normal ageing, the MMN amplitude was attenuated and peak latency prolonged. Besides indexing decreased discrimination accuracy, these effects may also reflect, depending on the specific stimulus paradigm used, decreased sensory-memory duration, abnormal perception or attention control or, most importantly, cognitive decline. In fact, MMN deficiency appears to index cognitive decline irrespective of the specific symptomatologies and aetiologies of the different disorders involved.     

Pathophysiology of primary burning mouth syndrome

Primary burning mouth syndrome (BMS) is severe, disabling and chronic intraoral pain condition for which no local or systemic cause can be found and clinical examination is normal. It mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%. In addition to spontaneous burning pain, patients may complain of taste alterations. Recent neurophysiologic, psychophysical, neuropathological, and functional imaging studies have elucidated that several neuropathic mechanisms, mostly subclinical, act at different levels of the neuraxis and contribute to the pathophysiology of primary BMS. Demonstration of loss of small diameter nerve fibres in the tongue epithelium explains thermal hypoesthesia and increase in taste detection thresholds found in quantitative sensory testing. As in neuropathic pain, decreased brain activation to heat stimuli has been demonstrated with fMRI in BMS patients. However, it seems that the clinical diagnosis of primary BMS encompasses at least three distinct, subclinical neuropathic pain states that may overlap in individual patients. The first subgroup (50-65%) is characterized by peripheral small diameter fibre neuropathy of intraoral mucosa. The second subgroup (20-25%) consists of patients with subclinical lingual, mandibular, or trigeminal system pathology that can be dissected with careful neurophysiologic examination but is clinically indistinguishable from the other two subgroups. The third subgroup (20-40%) fits the concept of central pain that may be related to hypofunction of dopaminergic neurons in the basal ganglia. The neurogenic factors acting in these subgroups differ, and will require different treatment strategies. In the future, with proper use of diagnostic tests, BMS patients may benefit from interventions specifically targeted at the underlying pathophysiological mechanisms.     

Effective Connectivity of the Human Cerebellum during Visual Attention

Insights from both lesion and neuroimaging studies increasingly substantiate the view that the human cerebellum not only serves motor control but also supports various cognitive processes. Higher cognitive functions like working memory or executive control have been associated with the phylogenetically younger parts of the cerebellum, crus I and crus II. Functional connectivity studies corroborate this notion as activation of the cerebellum correlates with activity in numerous areas of the cerebral cortex. Moreover, these cerebrocerebellar loops were shown to be topographically organized. We used an attention-to-motion paradigm to elaborate on the effective connectivity of cerebellar crus I during visual attention. Psychophysiological interaction analyses demonstrated enhanced connectivity of the cerebellum-during attention-with dorsal visual stream regions including posterior parietal cortex (PPC) and left secondary visual cortex (V5). Dynamic causal modeling revealed a modulation of the connections from V5 to PPC and from crus I to V5 by attention. Remarkably, the influence which V5 exerted on PPC was reduced during attention, resulting in a suppression of the sensitivity of PPC to bottom-up information. Moreover, the sensitivity of V5 populations to inputs from crus I was increased under attention. This might underscore the presumed role of the cerebellum as a state estimator that provides hierarchically lower regions (V5) with top-down predictions, which in turn might be based on endogenous inputs from PPC to the cerebellum. These results are in line with formulations of attention in predictive coding, where attention increases the precision or sensitivity of hierarchically lower neuronal populations that may encode prediction error.     

Clinical outcomes of myelomeningocele defect closure over 10 years

We report our surgical procedures for the closure of myelomeningocele defects. A retrospective analysis of 162 patients (74 male [45.7%], 88 female [54.3%]) with myelomeningocele was performed and the relationship between hydrocephalus, neurological status and the level and size of the myelomeningocele was described according to type of defect closure. Patients were divided into four groups according to the size of the defect, which was classified into ranges of 0-24 cm(2), 25-39 cm(2), 40-60 cm(2) and >60 cm(2). Myelomeningocele occurred in the lumbar region in 114 patients (70%). The minimum defect size was 3×2 cm, and the maximum defect size was 15×15 cm (mean defect size=34.64 cm(2)). We found that primary closure can be performed on clean, small defects with an intact sac that contains cerebrospinal fluid and the neural placode. For defects larger than 25 cm(2) that contained perforated sacculas, more soft tissue for well-vascularized coverage was required. Bilateral V-Y fasciocutaneous flaps are a good choice for immediate coverage of myelomeningocele defects.     

Cerebral vein thrombosis as an exceptional cause of transient ischemic attack

We present a case of transient ischemic attack (TIA) as an extremely rare presentation of cerebral vein thrombosis. A 41-year-old man presented with a headache and episodes of hypoesthesia on his left side lasting approximately 30 minutes. Several vascular risk factors were remarkable in his medical history. The neurologic examination was normal. TIA of arterial origin was excuded by detailed investigations. Magnetic resonance imaging revealed acute thrombosis of the right superficial middle cerebral vein and the vein of Trolard. TIA-like episodes stopped with anticoagulation. Head trauma a few days earlier was the most likely mechanism of venous thrombosis. We suggest that the patients with TIA and headache should be carefully investigated in terms of cerebral venous thrombosis.     

Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies

Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants.     

Safety of video-EEG monitoring and surgical outcome in patients with mesial temporal sclerosis and psychosis of epilepsy

PurposeCortico-amygdalohippocampectomy (CAH) has become an important treatment option for patients with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS); it has resulted in a 60–70% seizure remission rate and significant quality of life (QOL) improvements. Video-electroencephalography (VEEG) monitoring has been widely used in epilepsy centers for pre-surgical evaluation. A major concern in epilepsy surgery is whether to consider CAH treatment in patients with psychosis of epilepsy (POE). This study analyzed the safety and adverse events (AEs) of VEEG monitoring and the post-surgical outcomes of patients with refractory TLE-MTS and POE who underwent CAH.MethodClinical, sociodemographic and VEEG data from 18 patients with TLE-MTS and POE were analyzed. Psychiatric evaluations were performed using DSM-IV and ILAE criteria. The seizure outcome was evaluated using Engel's criteria.ResultsTwo patients (11.2%) presented AEs that did not result in increased lengths of hospitalization. Of the 10 patients (55.5%) who underwent CAH, 6 (60%) became free of disabling seizures (Engel I). The psychiatric and QOL evaluations revealed improvements of psychotic symptoms (p = 0.01) and in Physical Health (p = 0.01) following surgery.ConclusionThese data reinforce that VEEG monitoring is a safe method to evaluate patients with refractory TLE-MTS and POE in epilepsy centers.