Current concepts in the management of pyogenic brain abscesses

Brain abscesses are severe infections with lethal outcome in the case of delay in diagnosis and treatment. The authors report their experience about 30 patients with pyogenic brain abscesses treated between 1989 and 2000. The goal of the study is to analyse epidemiological, clinical and therapeutic aspects of this disease. The sex ratio (M:W) was 2,3 and the mean age was 34 years. Predisposing factors were sepsis of adjacent organs (53%) and bacteremia (30%). The clinical manifestations were: fever (83%), headaches (90%) and focal neurologic signs (57%). CT-scan findings were single lesions in 80% of cases. CT-scan showed a deep ring-enhancing lesion with surrounding edema in 77% of cases. Bacteriological agents in 13 cases (43%) were: 4 Staphylococcus aureus, 2 Neisseria meningitidis and 7 negative Gram bacilli. Medical treatment alone was in 77% of cases; seven patients benefited from medical and neurosurgical approaches. Death occured in 10% of cases.     

Urtica dioica attenuates ovalbumin-induced inflammation and lipid peroxidation of lung tissues in rat asthma model

Context: To find bioactive medicinal herbs exerting anti-asthmatic activity, we investigated the effect of an aqueous extract of Urtica dioica L. (Urticaceae) leaves (UD), the closest extract to the Algerian traditional use.

Objective: In this study, we investigated the in vivo anti-asthmatic and antioxidant activities of nettle extract.

Materials and methods: Adult male Wistar rats were divided into four groups: Group I: negative control; group II: Ovalbumin sensitized/challenged rats (positive control); group III: received UD extract (1.5?g/kg/day) orally along the experimental protocol; group IV: received UD extract (1.5?g/kg/day) orally along the experimental protocol and sensitized/challenged with ovalbumin. After 25?days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. The oxidative stress parameters were evaluated in the lungs, liver and erythrocytes. Then, correlations between markers of airway inflammation and markers of oxidative stress were explored.

Results: UD extract significantly (p?p?50 value.

Conclusions: The results confirmed that UD administration might be responsible for the protective effects of this extract against airway inflammation.     

Attenuated store-operated divalent cation entry and association between STIM1, Orai1, hTRPC1 and hTRPC6 in platelets from type 2 diabetic patients

Agonist-evoked Ca(2+) entry has been reported to be enhanced in platelets from type 2 diabetic patients, which results in altered platelet responsiveness and cardiovascular complications. The present study is aimed to investigate whether store-operated divalent cation entry, a major Ca(2+) entry pathway, is altered in platelets from diabetic patients. Store-operated divalent cation entry was estimated by determination of Mn(2+) entry. Association between STIM1, Orai1, hTRPC1 and hTRPC6 was detected by co-immunoprecipitation and Western blotting. In the presence of specific purinergic and serotoninergic receptor antagonists Mn(2+) entry, induced by thapsigargin (TG), was reduced in platelets from diabetic donors as compared to healthy controls. Treatment with TG or the agonist thrombin enhanced co-immunoprecipitation of STIM1 with Orai1, hTRPC1 and hTRPC6 in platelets from healthy donors, a response that was significantly reduced in platelets from diabetic patients. Our results indicate that store-operated divalent cation entry is reduced in platelets from type 2 diabetic subjects, which is likely mediated by impairment of the association of STIM1 with the channel subunits Orai1, hTRPC1 and hTRPC6 and might be involved in the pathogenesis of the altered platelet responsiveness observed in diabetic patients.     

From the Cover: Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model

Understanding the potential of nanomaterials (NMs) to cross the blood–brain barrier (BBB), as a function of their physicochemical properties and subsequent behavior, fate, and adverse effect beyond that point, is vital for evaluating the neurological effects arising from their unintentional entry into the brain, which is yet to be fully explored. This is not only due to the complex nature of the brain but also the existing analytical limitations for characterization and quantification of NMs in the complex brain environment. By using a fit-for-purpose analytical workflow and an in vitro BBB model, we show that the physiochemical properties of metallic NMs influence their biotransformation in biological matrices, which in turn modulates the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, their neurotoxicity. The data presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs.

More than a few decades have passed since the application of nanomaterials (NMs) in medicine and since the concept of nanotoxicity was formulated (1). Despite the time lapsed, concerns regarding their potential neurotoxicity (2) have yet to be fully addressed, primarily because of challenges in characterization resulting from their unique physicochemical properties. Recent studies found NMs (e.g., ZnO and magnetite NMs) can accumulate in the brain with distinct morphologies and forms that differ from their pristine counterpart, which can affect the cholinergic neurotransmission and thus brain health (3, 4). Beyond their safety, also important is the potential of NMs to act as carriers for medical interventions to the brain (e.g., to treat neurodegenerative conditions) (5).To date, our understanding of NM biotransformation in a biological matrix and their subsequent behavior and adverse effects remains limited because of the limitation in analytical techniques capable of tracing the transformation of such small particles in biological samples. This is even more challenging when quantifying the cellular uptake of the transformed NMs, because the unique physicochemical properties of NMs (i.e., small size, high specific surface area, high free surface energy, etc.) not only can modulate their biotransformation (6) and consequently their cellular uptake but also can directly influence the cellular penetration pathway and intracellular trafficking of NMs (7). This is of paramount importance for blood–brain barrier (BBB) cells, as the penetration and trafficking pathways could influence the number and forms of NMs entering the brain and possibly exerting adverse effects to the brain (e.g., inducing neurotoxicity) (8, 9). For instance, the biotransformation of nanoparticles (e.g., ZnO) in the brain and subbrain region (hippocampus) has been reported (3, 10).Inhaled, ingested, and dermally applied NMs can reach the blood stream (11). From there, there is a possibility that NMs in the bloodstream can cross the BBB and then directly or indirectly impact on the central nervous system (CNS) (12). The BBB is a physical barrier composed of a tightly packed layer of endothelial cells surrounding the brain, which separates the blood from the cerebrospinal fluid, allowing the transfer of oxygen and essential nutrients but preventing the access of most molecules. NMs function at the nanoscale; bind critical transport proteins such as apolipoproteins, including the brain transporter apolipoprotein E (13); and thus may have better ability to be transported across the BBB via endocytosis or diffusion (14, 15). Moreover, their biotransformation may dynamically alter their mobility and transport pathways. While emerging human (4) and in vivo (3) evidence suggests that NMs can deposit in brain regions, it is not clear whether these NMs enter the brain through the BBB pathway, what form(s) (i.e., pristine or transformed forms) and quantity of NMs enter the brain, and how the physicochemical properties of NMs modulate this penetration. Moreover, the fate of NMs within and beyond the BBB (i.e., the translocation, deposition, distribution, transformation, and adverse effect during and after crossing the BBB) is largely unknown, primarily because of the limited capacity of animal testing and difficulties in direct quantitative analysis of NMs within and beyond the barrier at molecular and cellular levels in real time. These knowledge gaps highlight the importance of using such approaches to enable a breakthrough in our fundamental understanding of the BBB penetration ability of NMs and the relevance of physicochemical properties on controlling the path, behavior, and impacts of NMs beyond the BBB.Here, we synthesized a library of metallic NMs with different particle compositions, sizes, and shapes and evaluated their ability to penetrate the BBB using a well-established in vitro BBB model, followed by an assessment of their behavior and fate in and beyond the BBB. To achieve this, a set of state-of-the-art analytical techniques, including single-particle inductively coupled plasma mass spectrometry (spICP-MS), synchrotron radiation–based X-ray absorption fine structure spectroscopy (XAFS), and high spatial resolution (20 nm) scanning transmission X-ray microscopy (STXM), and a series of biological assays were applied. We found that physiochemical properties of metallic NMs influenced their biotransformation in the physiological matrix. Biotransformation, in turn, modulated the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, the neurotoxicity. For example, spherical Ag (Ag NS) and disk-like Ag (Ag ND) NMs underwent different dissolution regimes in the physiological media and gradual transformation to Ag-sulfur compounds within the BBB, which facilitated paracellular and transcytosis entry pathways. Our finding showed that by changing the chemical composition of NMs to ZnO, CeO₂, and Fe₃O₄, the transport efficiency and amount of particles passing through the BBB change significantly, even if the shape and the size of the particles are kept the same. This can be linked to the composition-related biotransformation of the NMs, as CeO₂ and Fe₃O₄ NMs with low dissolution have the limited ability to transport across the BBB.     

Tumor necrosis factor gene polymorphisms in Tunisian patients with Behcet's disease

Behcet's disease (BD) is an inflammatory disorder that is mainly characterized by recurrent oral and genital ulcers, skin lesions, and uveitis. Recent reports focused on the genetic factors of susceptibility to this disease and especially the TNF in view of the major role played by this proinflammatory cytokine in the lesional process of Behcet's disease. In this report, we investigated the possible association between Behcet's disease and the TNF-alpha gene promoter polymorphisms -1031T/C, -308A/G, and the TNF-beta polymorphism +252A/G in Tunisian population. We compared the distribution of these polymorphisms between 89 BD patients and 157 healthy controls using polymerase chain reaction restriction fragment length-polymorphism (PCR-RFLP) analysis. The frequency of the TNF-alpha -1031C allele was significantly higher in Behcet's patients than in healthy controls (p = 0.015; chi(2) = 5.84; OR = 1.65; 95% CI = 1.08-2.54), whereas the frequencies of the TNF-alpha -308G and the TNF-beta +252G alleles were similar in the two compared groups. These results suggest that the variability of the TNF-alpha -1031T/C polymorphism can be associated with the susceptibility to Behcet's disease in our study group. Therefore, the TNF molecule may have an important genetically and/or functionally implication in the pathogenesis of BD in the Tunisian population.