Ethnomedicine survey on folk dermatology in Transylvania, Romania.

From the beginning of recorded history through the present day, dermatologic disorders have been treated with ethnomedicine remedies. We present the ethnodermatologic practices in Transylvania, Romania. We conducted ethnomedicine surveys in 35 villages in Transylvania (2007-2019). The 650 people interviewed were questioned about the treatment of dermatologic disorders by drugs derived from plant, animal, human, or other origins. Collected data were compared to earlier records of the regions and other European countries, completed with relevant pharmacologic studies of some plants. A total of 180 drugs were documented for 45 skin problems, including 112 plants, 1 fungus, 19 animals, 5 humans, and 43 other materials used in 11 preparation forms. Among these, 144 drugs were mentioned in humans, 10 in veterinary medicines, and 26 included in both therapies with overlapping human/animal (eg, Petroselinum crispum) and specific uses (eg, Daphne mezereum, Scrophularia nodosa). Compared to data from other countries, the local use of 32 plants and various animals and minerals was described only in the study area. The present study demonstrates that ethnomedicine practices are a valuable source of knowledge for skin diseases and highlight the relevance of fieldwork in the selected regions of Transylvania.

The Activities of the Gelsolin Homology Domains of Flightless-I in Actin Dynamics.

Flightless-I is a unique member of the gelsolin superfamily alloying six gelsolin homology domains and leucine-rich repeats. Flightless-I is an established regulator of the actin cytoskeleton, however, its biochemical activities in actin dynamics are still largely elusive. To better understand the biological functioning of Flightless-I we studied the actin activities of Drosophila Flightless-I by in vitro bulk fluorescence spectroscopy and single filament fluorescence microscopy, as well as in vivo genetic approaches. Flightless-I was found to interact with actin and affects actin dynamics in a calcium-independent fashion in vitro. Our work identifies the first three gelsolin homology domains (1-3) of Flightless-I as the main actin-binding site; neither the other three gelsolin homology domains (4-6) nor the leucine-rich repeats bind actin. Flightless-I inhibits polymerization by high-affinity (∼nM) filament barbed end capping, moderately facilitates nucleation by low-affinity (∼µM) monomer binding, and does not sever actin filaments. Our work reveals that in the presence of profilin Flightless-I is only able to cap actin filament barbed ends but fails to promote actin assembly. In line with the in vitro data, while gelsolin homology domains 4-6 have no effect on in vivo actin polymerization, overexpression of gelsolin homology domains 1-3 prevents the formation of various types of actin cables in the developing Drosophila egg chambers. We also show that the gelsolin homology domains 4-6 of Flightless-I interact with the C-terminus of Drosophila Disheveled-associated activator of morphogenesis formin and negatively regulates its actin assembly activity.

Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury.

PACAP has well-known neuroprotective potential including traumatic brain injury (TBI). Its level is up-regulated following various insults of the CNS in animal models. A few studies have documented alterations of PACAP levels in human serum. The time course of post-ictal PACAP levels, for example, show correlation with migraine severity. Very little is known about the course of PACAP levels following CNS injury in humans and the presence of PACAP has not yet been detected in cerebrospinal fluid (CSF) of subjects with severe TBI (sTBI). The aim of the present study was to determine whether PACAP occurs in the CSF and plasma (Pl) of patients that suffered sTBI and to establish a time course of PACAP levels in the CSF and Pl. Thirty eight subjects with sTBI were enrolled with a Glasgow Coma Scale ≤8 on admission. Samples were taken daily, until the time of death or for maximum 10 days. Our results demonstrated that PACAP was detectable in the CSF, with higher concentrations in patients with TBI. PACAP concentrations markedly increased in both Pl and CSF in the majority of patients 24-48h after the injury stayed high thereafter. In cases of surviving patients, Pl and CSF levels displayed parallel patterns, which may imply the damage of the blood-brain barrier. However, in patients, who died within the first week, Pl levels were markedly higher than CSF levels, possibly indicating the prognostic value of high Pl PACAP levels.

Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms.

BACKGROUND AND PURPOSE: According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. The aim of the study was to assess whether AcoA aneurysms behave differently from other AC aneurysms. METHODS: Information about 932 patients newly diagnosed with intracranial aneurysms between November 1, 2006, and March 31, 2012, including aneurysm status at diagnosis, its location, size, and risk factors, was collected during the multicenter @neurIST project. For each location or location and size subgroup, the odds ratio (OR) of aneurysms being ruptured at diagnosis was calculated. RESULTS: The OR for aneurysms to be discovered ruptured was significantly higher for AcoA (OR, 3.5 [95% confidence interval, 2.6-4.5]) and posterior circulation (OR, 2.6 [95% confidence interval, 2.1-3.3]) than for AC excluding AcoA (OR, 0.5 [95% confidence interval, 0.4-0.6]). Although a threshold of 7 mm has been suggested by ISUIA as a threshold for aggressive treatment, AcoA aneurysms <7 mm were more frequently found ruptured (OR, 2.0 [95% confidence interval, 1.3-3.0]) than AC aneurysms of 7 to 12 mm diameter as defined in ISUIA. CONCLUSIONS: We found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Intervention should be recommended for this high-risk lesion group.

Multi-modal magnetic resonance imaging in the acute and sub-acute phase of mild traumatic brain injury: can we see the difference?

Advanced magnetic resonance imaging (MRI) methods were shown to be able to detect the subtle structural consequences of mild traumatic brain injury (mTBI). The objective of this study was to investigate the acute structural alterations and recovery after mTBI, using diffusion tensor imaging (DTI) to reveal axonal pathology, volumetric analysis, and susceptibility weighted imaging (SWI) to detect microhemorrhage. Fourteen patients with mTBI who had computed tomography with negative results underwent MRI within 3 days and 1 month after injury. High resolution T1-weighted imaging, DTI, and SWI, were performed at both time points. A control group of 14 matched volunteers were also examined following the same imaging protocol and time interval. Tract-Based Spatial Statistics (TBSS) were performed on DTI data to reveal group differences. T1-weighted images were fed into Freesurfer volumetric analysis. TBSS showed fractional anisotropy (FA) to be significantly (corrected p<0.05) lower, and mean diffusivity (MD) to be higher in the mTBI group in several white matter tracts (FA=40,737; MD=39,078 voxels) compared with controls at 72 hours after injury and still 1month later for FA. Longitudinal analysis revealed significant change (i.e., normalization) of FA and MD over 1 month dominantly in the left hemisphere (FA=3408; MD=7450 voxels). A significant (p<0.05) decrease in cortical volumes (mean 1%) and increase in ventricular volumes (mean 3.4%) appeared at 1 month after injury in the mTBI group. SWI did not reveal microhemorrhage in our patients. Our findings present dynamic micro- and macrostructural changes occurring in the acute to sub-acute phase in mTBI, in very mildly injured patients lacking microhemorrhage detectable by SWI. These results underscore the importance of strictly defined image acquisition time points when performing MRI studies on patients with mTBI.

Effect of PACAP in central and peripheral nerve injuries.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a bioactive peptide with diverse effects in the nervous system. In addition to its more classic role as a neuromodulator, PACAP functions as a neurotrophic factor. Several neurotrophic factors have been shown to play an important role in the endogenous response following both cerebral ischemia and traumatic brain injury and to be effective when given exogenously. A number of studies have shown the neuroprotective effect of PACAP in different models of ischemia, neurodegenerative diseases and retinal degeneration. The aim of this review is to summarize the findings on the neuroprotective potential of PACAP in models of different traumatic nerve injuries. Expression of endogenous PACAP and its specific PAC1 receptor is elevated in different parts of the central and peripheral nervous system after traumatic injuries. Some experiments demonstrate the protective effect of exogenous PACAP treatment in different traumatic brain injury models, in facial nerve and optic nerve trauma. The upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central and peripheral nerve injuries show the important function of PACAP in neuronal regeneration indicating that PACAP may also be a promising therapeutic agent in injuries of the nervous system.

A biexponential DWI study in rat brain intracellular oedema.

PURPOSE: To examine the changes in MR parameters derived from diffusion weighted imaging (DWI) biexponential analysis in an in vivo intracellular brain oedema model, and to apply electron microscopy (EM) to shed more light on the morphological background of MR-related observations. MATERIALS AND METHODS: Intracellular oedema was induced in ten male Wistar rats (380-450g) by way of water load, using a 20% body weight intraperitoneal injection of 140mmol/L dextrose solution. A 3T MRI instrument was used to perform serial DWI, and MR specroscopy (water signal) measurements. Following the MR examination the brains of the animals were analyzed for EM. RESULTS: Following the water load induction, apparent diffusion coefficient (ADC) values started declining from 724±43µm(2)/s to 682±26µm(2)/s (p<0.0001). ADC-fast values dropped from 948±122 to 840±66µm(2)/s (p<0.001). ADC-slow showed a decrease from 226±66 to 191±74µm(2)/s (p<0.05). There was a shift from the slow to the fast component at 110min time point. The percentage of the fast component demonstrated moderate, yet significant increase from 76.56±7.79% to 81.2±7.47% (p<0.05). The water signal was increasing by 4.98±3.52% compared to the base line (p<0.01). The results of the E.M. revealed that water was detected intracellularly, within astrocytic preivascular end-feet and cell bodies. CONCLUSION: The unexpected volume fraction changes (i.e. increase in fast component) detected in hypotonic oedema appear to be substantially different from those observed in stroke. It may suggest that ADC decrease in stroke, in contrast to general presumptions, cannot be explained only by water shift from extra to intracellular space (i.e. intracellular oedema).

The influence of benzamil hydrochloride on the evolution of hyponatremic brain edema as assessed by in vivo MRI study in rats.

OBJECTIVE: The present study was undertaken to reveal the influence of intracerebroventricular (ICV) benzamil on the dynamics of brain water accumulation in hyponatremic rats. Parameters of brain water homeostasis were continuously monitored, using in vivo magnetic resonance imaging (MRI) methods. The results were compared with those obtained in a previous study by tissue desiccation. METHODS: A 3-T MRI instrument was applied to perform serial diffusion-weighted imaging to measure the apparent diffusion coefficient (ADC) and MR spectroscopy to determine water signal. A decrease of ADC is thought to represent an increase of intracellular water, whereas water signal is used to quantify brain water content. Five groups of male Wistar rats were studied as follows: normonatremic, native animals (group NN, n = 7), hyponatremic animals (group HN, n = 8), hyponatremic animals treated with ICV benzamil (group HNB, n = 8), hyponatremic animals treated with ICV saline (group HNS, n = 5) and normonatremic animals treated with ICV benzamil (group NNB, n = 5). Hyponatremia was induced by intraperitoneal administration of 140 mmol/l dextrose solution in a dose of 20% of body weight. Benzamil hydrochloride (4 µg) was injected ICV to the treated animals. RESULTS: During the course of hyponatemia, ADC declined steadily from the baseline (100%) to reach a minimum of 92.32 ± 3.20% at 90 min (p < 0.0005). This process was associated with an increase in water signal to a maximum of 5.95 ± 2.62% at 100 min (p < 0.0005). After pretreatment with benzamil, no consistent changes occurred either in ADC or in water signal. CONCLUSIONS: These findings suggest that sodium channel blockade with ICV benzamil has an immediate protective effect against the development of hyponatremic brain edema. Sodium channels, therefore, appear to be intimately involved in the initiation and progression of brain water accumulation in severe hyponatremia.

A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury: an immunohistochemical and behavioral study.

We examined the neuro/axono-protective potential of a novel poly (ADP-ribose) polymerase (PARP) inhibitor L-2286 in a rat impact acceleration brain injury model. Male Wistar rats (n = 70) weighing 300-350 grams were used to determine the most effective intracerebroventricular (i.c.v.) dose of L-2286 administered 30 min after injury, and to test the neuroprotective effect at two time points (immediately, and 30 min after injury). The neuroprotective effect of L-2286 was tested using immunohistochemical (amyloid precursor protein and mid-sized mouse anti-neurofilament clone RMO-14.9 antibody) and behavioral tests (beam-balance, open-field and elevated plus maze). At both time-points, a 100 microg/rat dose of i.c.v. L-2286 significantly (p < 0.05) reduced the density of damaged axons in the corticospinal tract and medial longitudinal fascicle compared to controls. In the behavioral tests, treatment 30 min post-injury improved motor function, while the level of anxiety was reduced in both treatment protocols.

Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics.

PURPOSE: This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma. METHODS: We performed an electronic search of the National Library of Medicine's MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-beta(1-42)) in the last 10 years, but recent data on "classical" markers (S-100B, neuron-specific enolase, etc.) were also examined. RESULTS: We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment. CONCLUSIONS: We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.

Calpain inhibition reduces axolemmal leakage in traumatic axonal injury.

Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

Supravital microwave experiments support that the formation of "dark" neurons is propelled by phase transition in an intracellular gel system.

BACKGROUND: Based on circumstantial evidences, we (Gallyas, F., Farkas, O., Mázló, M., 2004. Gel-to-gel phase transition may occur in mammalian cells: Mechanism of formation of "dark" (compacted) neurons. Biol. Cell 96, 313-324.) proposed that the formation of "dark" neurons (striking compaction of visibly normal ultrastructural elements accompanied with large-scale fluid excretion), which occur in many neurological diseases such as ischemia, proceeds with a non-enzymatic mechanism. OBJECTIVE: To support this proposition, the present paper deals with the results of supravital experiments using microwave irradiation. METHOD: After transcardial glutaraldehyde fixation followed by decapitation, a pin was stuck into rat brains just before and just after they were warmed up to 80 degrees C and maintained at this temperature for various periods of time by controlled microwave irradiation. RESULTS: Independently of the duration of irradiation, the pre-irradiation pin sticking produced numerous "dark" neurons in an approximating 500-microm-wide zone around its track whereas the post-irradiation pin sticking did the same only when the irradiation was shorter than 55 s. The excreted fluid was present in neighbouring astrocytic processes but not in the extracellular space. CONCLUSIONS: The formation of "dark" neurons is completed in less than 55 s under the circumstances of the experiment. As neurons are poor in readily consumable chemical energy in the absence of blood circulation, this rapid and massive fluid excretion cannot be explained by any enzyme-mediated membrane-related pump mechanism. An osmotic mechanism can also be discounted. In contrast, it is in conformity with the above mentioned non-enzymatic (physicochemical) phenomenon, the phase transition of a supra-cytoskeletal gel network storing free energy in the form of non-covalent interactions.

Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats.

Several in vitro and in vivo experiments have demonstrated the neuroprotective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in focal cerebral ischemia, Parkinson's disease and traumatic brain injury (TBI). The aim of the present study was to analyze the effect of PACAP administration on diffuse axonal injury (DAI), an important contributor to morbidity and mortality associated with TBI, in a central fluid percussion (CFP) model of TBI. Rats were subjected to moderate (2 Atm) CFP injury. Thirty min after injury, 100 microg PACAP was administered intracerebroventricularly. DAI was assessed by immunohistochemical detection of beta-amyloid precursor protein, indicating impaired axoplasmic transport, and RMO-14 antibody, representing foci of cytoskeletal alterations (neurofilament compaction), both considered classical markers of axonal damage. Analysis of damaged, immunoreactive axonal profiles revealed significant axonal protection in the PACAP-treated versus vehicle-treated animals in the corticospinal tract, as far as traumatically induced disturbance of axoplasmic transport and cytoskeletal alteration were considered. Similarly to our former observations in an impact acceleration model of diffuse TBI, the present study demonstrated that PACAP also inhibits DAI in the CFP injury model. The finding indicates that PACAP and derivates can be considered potential candidates for further experimental studies, or purportedly for clinical trials in the therapy of TBI.

Traumatic axonal injury in the spinal cord evoked by traumatic brain injury.

Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n = 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI.

Morphological effects of transcardially perfused SDS on the rat brain.

BACKGROUND INFORMATION: For explanation of the formation of 'dark' neurons, an enigmatic phenomenon in neuropathology, we hypothesized recently that all spaces between the ultrastructural elements visible in the traditional transmission electron microscope are filled with a gel structure that stores free energy in the form of non-covalent interactions, is continuous in the whole soma-dendrite domains of neurons, and is capable of whole-cell phase transition. This hypothesis was deduced from the fact that 'dark' neurons can be formed, even under conditions extremely unfavourable for enzyme-mediated biochemical processes, if initiated by a physical damage. In order to gain further information on this gel structure, we perfused transcardially rats for 5 min with physiological saline containing 1 mM SDS before the perfusion of a fixative for electron microscopy. RESULTS: Dramatic compaction of visibly intact ultrastructural elements was caused in the whole soma-dendrite domains of thinly scattered neurons ('dark' neurons), whereas substantial cytoplasmic swelling and patchy ultrastructural disintegration occurred in numerous other neurons ('light' neurons). Similar morphological changes were observed in scattered astrocytes, oligodendrocytes, pericytes and endothelial cells. CONCLUSIONS: These observations: (i) support the existence of the above intracellular gel structure in neurons; (ii) allow the conclusion that this gel structure is present in the form of an ubiquitous trabecular network surrounded by a confluent system of fluid cytoplasm; (iii) draw attention to the possibility that the previous two statements also apply to other cell types of the brain tissue; and (iv) suggest that pressure-induced direct channels exist between neurons and astrocytes.