MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Intracranial dural based marginal zone MALT-type B-cell lymphoma: a case - Based update and literature review.

OBJECTIVES: Dural based Marginal Zone MALT-type B-Cell Lymphoma (MZBCL) is an intracranial tumor that can mimicking meningioma both from a clinical and a radiological point of view. A standard treatment protocol is still lacking. Aim of the present work is to provide an update of the present literature regarding this rare neoplasia. PATIENTS AND METHODS: We report the case of a patient with a dural-based lesion mimicking a meningioma of the tentorium. After surgical treatment, the diagnosis was of MZBCL. A literature review is performed to highlight the typical characteristics of this rare intracranial lesion and to define the best therapeutic approach. RESULTS: Literature review included 38 articles describing 126 cases of intracranial dural-based MZBCL. No clinical trial has been found. Clinical and histopathological features are properly collected to provide a guide for future cases. Different treatment options have been attempted. Combination of surgery with adjuvant radiation therapy is the most used option. CONCLUSIONS: MZBCL should be considered in differential diagnosis for dural-based intracranial lesion. Surgery followed by radiation therapy is the most reported treatment. As a consequence of the rarity of this disease, of its indolent progression and of the lack of adequate follow-up, it is not possible to define it is the best treatment option.

Lumbo-sacral pedicular aplasia diagnosis and treatment: a systematic literature review and case report.

Aplasia of the lumbar pedicle is a rare condition, frequently associated with low back pain. Its recognition is fundamental in the definition of the correct treatment. We performed a literature review in order to clarify how to best diagnose and treat this rare anatomical condition. A comprehensive literature search for studies published through October 2020 was performed, using the following algorithm: "aplasia" OR "aplastic" OR "hypoplasia" OR "hypoplastic" OR "absent" OR absence" AND "pedicle" AND "lumbar" OR "sacral" OR "lumbosacral". References from reviewed papers were further evaluated for the inclusion of other relevant studies. Eighteen studies were included in the systematic review for a total of 24 adult patients. Another case of left L5 pedicle aplasia treated at our hospital has been described and included in the present review. This anatomical condition may be suspected in plain x-Ray, but CT scan 3D reconstructions may help to confirm the diagnosis in equivocal cases. Low-back pain and radiculopathy are the main signs and symptoms. The treatment was described in 14 cases. Eight patients underwent surgical intervention. In cases with spondylolisthesis, fusion surgery was performed with different techniques, obtaining an excellent clinical outcome. Pedicular aplasia is a rare condition that must be recognized in patients with a low back. When it is associated with spondylolisthesis, fusion surgery should be the preferred option.

Trans-sulcal versus trans-parenchymal approach in supratentorial cavernomas. A multicentric experience.

OBJECTIVES: Cavernous malformations (CM) are low-flow vascular lesions that can cause significant symptoms and neurological deficits. Different intraoperative surgical approaches have been developed. Aim of the present investigation is the comparison between the trans-sulcal approach (TS) and the trans-parenchymal neuronavigation-assisted approach (TPN) in a surgical series from two neurosurgical centers. The technique and clinical outcomes are discussed, with a specific focus on seizure outcome. PATIENTS AND METHODS: Clinical and radiological data from two neurosurgical centers ("A. Gemelli" Hospital in Rome and A.O.U. Città della Salute e della Scienza in Turin) were retrospectively reviewed in order to evaluate the different outcome of TS and TPN approach for cavernous malformation treatment. RESULTS: A total of 177 patients underwent surgical intervention for supratentorial CM, 130 patients with TPN approach and 47 with TS approach. TS approach was associated with higher rate of seizure in early post-operative period both in epileptic patients (p < 0,001) and in patients without history of seizures before surgery (p = 0,002). Moreover, length of incision (p < 0,001), area of craniotomy (p < 0,001) and corticectomy (p < 0,001) were bigger in TS than in TPN approach. Brain contusion (p < 0,001) and fluid collection (p < 0,001) were more likely to be discovered after TS approach. CONCLUSIONS: TPN is a valuable approach for resection of CM. Minor complications are significantly lower in TPN approach when compared with TS approach. In addition, it is associated with lower rate of early post-operative seizure and shorter length of stay.

Frequency of allergic sensitization to Can f 5 in North East Italy. An analysis of 1403 ISACs 112 (Component Resolved Diagnosis) collected retrospectively.

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5, a prostatic kallicrein expressed in the prostate and detectable only in male dogs. The aim of the present study was to establish the frequency, level of sensitization and association with other dog allergens of Can f 5, as assessed by Component Resolved Diagnosis (CRD- ISAC 112, ThermoFisher Scientific, Uppsala, Sweden), in North East Italy. A total of 1403 CRD ISAC 112 were examined retrospectively. Five-hundred twenty subjects (37 %) had a positive IgE response to at least one of the available animal allergens. Among these 520 subjects, 268 (51.5 %) showed at least one sensitization to dog allergens. Among dog-sensitized individuals, 183 (69.02%) showed IgE against Can f 5, and 106 (57.92%) were sensitized exclusively against Can f 5. The average Can f 5 specific IgE was 8.810 ISU-E, with 77.6 % of individuals showing medium or high values of specific IgE according to manufacturer's specifications. In conclusions, our data confirmed that there is a high number of sensitized patients to Can f 5, which have a high degree of allergic sensitization. These results should be taken into account by allergists managing dog allergic patients. In fact, clinical consequences of this sensitization regard respiratory allergy (burden of rhinitis/asthma), systemic reactions (anaphylaxis during sexual intercourse from cross-reaction with human prostatic antigen), allergen immunotherapy-AIT (likely ineffective in patients with exclusive sensitization), and preventive measures (possibility to own a female dog and a likely reduction of allergen passive transport). Further studies are needed to better explore these aspects in "real life".

Modeling interaction between gp120 HIV protein and CCR5 receptor.

The study of the process of HIV entry into the host cell and the creation of biomimetic nanosystems that are able to selectively bind viral particles and proteins is a high priority research area for the development of novel diagnostic tools and treatment of HIV infection. Recently, we described multilayer nanoparticles (nanotraps) with heparin surface and cationic peptides comprising the N-terminal tail (Nt) and the second extracellular loop (ECL2) of CCR5 receptor, which could bind with high affinity some inflammatory chemokines, in particular, Rantes. Because of the similarity of the binding determinants in CCR5 structure, both for chemokines and gp120 HIV protein, here we expand this approach to the study of the interactions of these biomimetic nanosystems and their components with the peptide representing the V3 loop of the activated form of gp120. According to surface plasmon resonance results, a conformational rearrangement is involved in the process of V3 and CCR5 fragments binding. As in the case of Rantes, ECL2 peptide showed much higher affinity to V3 peptide than Nt (KD  = 3.72 × 10-8 and 1.10 × 10-6  M, respectively). Heparin-covered nanoparticles bearing CCR5 peptides effectively bound V3 as well. The presence of both heparin and the peptides in the structure of the nanotraps was shown to be crucial for the interaction with the V3 loop. Thus, short cationic peptides ECL2 and Nt proved to be excellent candidates for the design of CCR5 receptor mimetics.

The post-surgical era of GBM: How molecular biology has impacted on our clinical management. A review.

Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies. We have also analyzed the cellular biology and the interactions between GBM and the surrounding environment.

Ferrous iron- and ammonium-rich diffuse vents support habitat-specific communities in a shallow hydrothermal field off the Basiluzzo Islet (Aeolian Volcanic Archipelago).

Ammonium- and Fe(II)-rich fluid flows, known from deep-sea hydrothermal systems, have been extensively studied in the last decades and are considered as sites with high microbial diversity and activity. Their shallow-submarine counterparts, despite their easier accessibility, have so far been under-investigated, and as a consequence, much less is known about microbial communities inhabiting these ecosystems. A field of shallow expulsion of hydrothermal fluids has been discovered at depths of 170-400 meters off the base of the Basiluzzo Islet (Aeolian Volcanic Archipelago, Southern Tyrrhenian Sea). This area consists predominantly of both actively diffusing and inactive 1-3 meters-high structures in the form of vertical pinnacles, steeples and mounds covered by a thick orange to brown crust deposits hosting rich benthic fauna. Integrated morphological, mineralogical, and geochemical analyses revealed that, above all, these crusts are formed by ferrihydrite-type Fe3+ oxyhydroxides. Two cruises in 2013 allowed us to monitor and sampled this novel ecosystem, certainly interesting in terms of shallow-water iron-rich site. The main objective of this work was to characterize the composition of extant communities of iron microbial mats in relation to the environmental setting and the observed patterns of macrofaunal colonization. We demonstrated that iron-rich deposits contain complex and stratified microbial communities with a high proportion of prokaryotes akin to ammonium- and iron-oxidizing chemoautotrophs, belonging to Thaumarchaeota, Nitrospira, and Zetaproteobacteria. Colonizers of iron-rich mounds, while composed of the common macrobenthic grazers, predators, filter-feeders, and tube-dwellers with no representatives of vent endemic fauna, differed from the surrounding populations. Thus, it is very likely that reduced electron donors (Fe2+ and NH4+ ) are important energy sources in supporting primary production in microbial mats, which form a habitat-specific trophic base of the whole Basiluzzo hydrothermal ecosystem, including macrobenthic fauna.

Diagnosis and management of dural arteriovenous fistulas: a 10 years single-center experience.

OBJECTIVES: Dural arteriovenous fistulas (DAVFs) are a challenging condition in vascular neurosurgery. Disease natural history and its management is still debated. In the present paper we report our center series on DAVFs over a period of 10 years. Our data were compared with relevant literature. PATIENT AND METHODS: Our series includes 45 cases: 14 cavernous sinus, 11 transverse-sigmoid, 8 patients tentorial, 6 anterior cranial fossa, 5 patients spinal, 1 patient foramen magnum. RESULTS AND CONCLUSIONS: DVAFs distribution, clinical presentation and hemorrhagic risk are discussed. Cavernous sinus DAVFs are the most common site in our series. Other locations in order of frequency are transverse-sigmoid sinus, tentorial, anterior cranial fossa, spinal and foramen magnum. The majority of patients presented with non-aggressive symptoms. 18% presented with intracranial hemorrhage: all the hemorrhages occurred in high-grade DAVFs. For most patients, endovascular treatment, transarterial or transvenous, was the first option. Surgery was performed for the anterior cranial fossa DAVFs and other complex lesions draining mostly transverse-sigmoid sinus and tentorium. In 7% of cases a combination of endovascular+surgical treatment was used. Our series has been carefully analyzed in comparison 'side by side' with most relevant literature on DVAFs, focusing particularly on management strategies, therapeutic options and risks related to treatment.

Indocyanine green video-angiography in neurosurgery: a glance beyond vascular applications.

OBJECTIVE: Indocyanine green video angiography (ICG-VA) is a non invasive, easy to use and a very useful tool for various neurosurgical procedures. Initially introduced in vascular neurosurgery since 2003, it's applications have broadened over time, both in vascular applications and in other neurosurgical fields. The objective of our study is to review all published literature about ICG-VA, cataloguing its different applications. METHODS: A systematic review of all pertinent literature articles published from January 2003 to May 2014 using Pubmed access was performed using pertinent keywords; cross check of references of selected articles was performed in order to complete bibliographical research. Results of research were grouped by pathology. RESULTS AND CONCLUSIONS: The paper systematically analyses ICG-VA different applications in neurosurgery, from vascular neurosurgery to tumor resection and endoscopic applications, focusing on reported advantages and disadvantages, and discussing future perspectives.

Comparison of beneficial actions of non-steroidal anti-inflammatory drugs to flavonoids.

Inflammation is involved in increasing number of diseases necessitating the development of new, effective and safe treatments. Non steroidal anti-inflammatory drugs (NSAIDs) have been helpful in many instances, but they only inhibit cyclooxygenase (COX), but not the generation or actions of cytokines. Instead, some natural flavonoids have multiple anti-inflammatory effects, including COX inhibition, and a much safer profile. Increasing evidence indicates that inflammation plays a critical role in the pathogenesis of many diseases that also involve mast cells. Consequently, the need for new, effective and safe anti-inflammatory drugs is all the more urgent. Corticosteroids are quite potent, but have many adverse effects such as increased risk of infections, osteoporosis, glaucoma and depression. Biological agents such anti-TNF are useful in certain conditions, such as rheumatoid arthritis and psoriasis, but has been associated with increased risk of infection and leukemia.

Glioblastoma multiforme intraxial metastasis to the conus medullaris with primary disease under control: a rare unexpected finding.

We report on glioblastoma multiple spinal intraaxial metastases with primary disease radiologically under control. The case highlights glioblastoma biological behavior and spread mechanisms; dissemination may have occurred initially and been controlled by chemotherapy, or more likely, is an indicator that even if radiologically dormant, disease is unlikely biologically inactive.

Nanotechnology and vascular neurosurgery: an in vivo experimental study on microvessels repair using laser photoactivation of a nanostructured hyaluronan solder.

Sealing tissues by laser in neurosurgical procedures may overcome problems related to the use of conventional suturing methods which can be associated with various degrees of vascular wall damage. Despite the significant experimental and clinical achievements of the past, a standardized clinical application of laser-welding technology has not yet been implemented. The main problem is related to the use of common organic chromophores. A substantial breakthrough in the laser welding of biological tissues may come from the advent of nanotechnologies. In this paper we describe an experimental study, to confirm the feasibility of an innovative laser-assisted vascular repair (LAVR) technique based on diode laser irradiation and subsequent photoactivation of a hyaluronan solder embedded with near infrared (NIR) absorbing gold nanorods (GNRs), and to analyze the induced closuring effect in a follow-up study performed in animal model. Twenty New Zealand rabbits underwent closure of a 3-mm longitudinal incision performed on the common carotid artery (CCA) by means of 810 nm diode laser irradiation, in conjunction with the topical application of an optimized GNR composite. Effective closure of the arterial wound was accomplished by using very low laser intensity (30 W/cm2). The average CCA occlusion time was as low as 50 sec. Animals underwent different follow-up periods (2, 8, 30 days). After follow-up, they were re-anesthetized, the patency of the treated vessels was tested (Doppler analysis) and then the irradiated vessels were excised and subjected to histological evaluations. Morphological examinations of the samples documented the integrity of the vascular wall. No host reaction to nanoparticles occurred. Collagen and elastic fibers returned to their normal architecture 30 days after treatment. A Scanning Electron Microscopy (SEM) examination and immuno-histochemical analysis demonstrated a full re-endothelization of the vessel walls. We thus confirmed that a laser-based approach is technically easy to perform, and provides several advantages, such as a simplification of the surgical procedure, a reduction in the operative time, and the suppression of bleeding. The use of GNRs improves the selectivity of welding and minimizes the surgical trauma to vessels, resulting in an optimal healing process.

Present status and new perspectives in laser welding of vascular tissues.

The laser welding of biological tissues is a particular use of lasers in surgery. The technique has been proposed since the 1970s for surgical applications, such as repairing blood vessels, nerves, tendons, bronchial fistulae, skin and ocular tissues. In vascular surgery, two procedures have been tested and optimized in animal models, both ex vivo and in vivo, in order to design different approaches for blood vessels anastomoses and for the repair of vascular lesions: the laser-assisted vascular anastomosis (LAVA) and the laser-assisted vessel repair (LAVR). Sealing tissues by laser may overcome the problems related to the use of conventional closuring methods that are generally associated with various degrees of vascular wall damage that can ultimately predispose to vessel thrombosis and occlusion. In fact, the use of a laser welding technique provides several advantages such as simplification of the surgical procedure, reduction of the operative time, suppression of bleeding, and may guarantee an optimal healing process of vascular structures, very similar to restitutio ad integrum. Despite the numerous preclinical studies performed by several research groups, the clinical applications of laser-assisted anastomosis or vessel repair are still far off. Substantial breakthrough in the laser welding of biological tissues may come from the advent of nanotechnologies. Herein we describe the present status and the future perspectives in laser welding of vascular structures.

Colonic mast cells in controls and slow transit constipation patients.

BACKGROUND: There is recent evidence that mast cells may play important roles in the gut, especially concerning visceral hypersensitivity and motor activity. However, most data are only available for clinical conditions characterised by diarrhoea, where MC have chiefly investigated in the mucosal layer of the colon and there is almost no information concerning constipation. AIM: To investigate mast cells distribution in all colonic layers in controls and severely constipated patients. METHODS: Full-thickness specimens from colons of patients undergoing surgery for slow transit constipation (n=29), compared with controls, were obtained and the number of mast cells (evaluated by specific monoclonal antibodies) counted as a whole and in single colonic segments (caecum, ascending, transverse, descending and sigmoid). RESULTS: Compared with controls, constipated patients revealed significantly higher number of mast cells, both as overall number and in single colonic segments. The distribution of mast cells resulted fairly homogeneous in the various segment of the large bowel, in both controls and patients, and no significant difference in the percentage of degranulated cells was found between groups. CONCLUSIONS: Colonic mast cells display a homogeneous distribution within the viscus. This cell population is shown to increase in severely constipated patients, which might represent a mechanism trying to compensate for the impaired propulsive activity of these patients.

An experimental study on minimally occlusive laser-assisted vascular anastomosis in bypass surgery: the importance of temperature monitoring during laser welding procedures.

Laser welding has been proposed as an alternative technique to conventional stitching in microvascular anastomosis, with the advantages of improving the vascular healing process and reducing the risk of malfunction of a bypass. Our group recently proposed a laser-assisted end-to-side anastomotic technique, providing the advantages of laser welding and reducing the occlusion time of the recipient vessel, that is important in neurosurgical bypass procedures, in order to reduce the risk of cerebral ischemia. This in vivo study focuses on the control of the temperature dynamics developing in the welded tissue. A jugular vein graft was harvested and implanted on the rabbit carotid artery by means of two end-to-side anastomosis. Laser welding procedure was then carried out to implant the bypass. A real-time monitoring of the temperature during welding was performed with an infrared thermocamera, in order to control the laser-induced heating effect on the external surface of the vessel walls. The temperature analysis highlighted the dynamic of the heating effect in space and time and enabled us to define an optimal temperature range in operative conditions. The temperature control provided safe tissue heating confined within the directly irradiated area, with negligible damage to surrounding tissues, as well as effective sealing and welding of the vessel edges at the anastomotic sites. The average occlusion time of the carotid artery was about 11 minutes. After a follow-up of 30 days, all the bypasses were patent and no signs of thrombosis or leak point pressure were present, thus confirming the safety of this laser-assisted anastomotic procedure.

Comparative evaluation of genome-wide gene expression profiles in ruptured and unruptured human intracranial aneurysms.

Few studies have evaluated the over or the underexpression of genes directly in samples of aneurysmal wall and extracranial pericranial vascular tissue to investigate the genetic influence in formation and rupture of intracranial aneurysms. We present the results obtained using the DNA microarray technique analysis on sample tissues collected during surgery. We collected and analyzed 12 aneurismal and 9 peripheral arteries (superficial temporal (STA) and middle meningeal artery (MMA) specimens from ruptured aneurysm group patients (13 cases), 10 aneurismal and 12 STA and MMA samples from unruptured aneurysm group patients (14 cases) and 5 STA and MMA artery specimens from control group patients (4 cases). Total RNA was isolated from samples and subjected to cDNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray (Affymetrix, Santa Clara, CA), which allows to analyze a total number of 14,500 genes in the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Total RNA was isolated from samples and subjected to DNA microarray analysis with the use of the human genome U133A GeneChip oligonucleotide microarray, which allows to analyze a total number of 14,500 genes at the same time. For genes of interest, real-time RT-PCR was performed to confirm their expression level. Regarding ruptured aneurysms, genes were identified showing differential expressions (overexpressed or downregulated) pertaining to specific pathways, particularly those for the structural proteins of the extracellular matrix, members of matrix metalloproteinase (MMP) family (which resulted as being overexpressed) and genes involved in apoptotic phenomena. Particularly, real-time RT-PCR analysis confirmed the upregulation of MMP-2, MMP-9 and pro-apoptotic genes, such as Fas, Bax and Bid, and the downregulation of anti-apoptotic genes, such as Bcl-X(L) and Bcl-2. In a compared analyses of ruptured vs unruptured aneurysms, a different expression was also detected regarding gene coding the tissue inhibitor of matrix metalloproteinases 3 (TIMP-3), which appeared markedly downregulated in unruptured aneurysms, where its expression in unruptured aneurysms was similar to that observed in controls. Another gene differently expressed is nitric oxide synthase (iNOS), which appeared overexpressed in ruptured aneurysms when compared to unruptured aneurysms. Our study is the first, to our knowledge, that compares gene expression profiles (genoma-wide) in intracranial aneurysms. The results of our study suggest that the inhibitor of the metalloproteinase, the pathway of nitric oxide and the apoptotic process play a key-role in reducing the resistance of the arterial wall, that can result in formation and rupture of the intracranial aneurysms.

Infections and mast cells.

Mast cells play a role in various physiological functions: innate and acquired immunity, epithelium remodelling and proliferation, angiogenesis, cancer, inflammation and infections. Mast cells are activated by cross-linking of FcERI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. In addition, mast cell biology consists in the capability to secrete preformed mediators which include biogenic amines and newly synthetized mediators, which include lipid-derived mediators and cytokines. It has been reported that parasite infections induce a systemic immunomodulatory network, including regulatory T cells, pro-inflammatory and anti-inflammatory cytokines, which might play a key role in the allergic phenotype. Here, in this article, we revisited the relationship between mast cells and infections.

Mast cells and chemokines.

Chemokines are small proteins (8-12 kD polypeptides) secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells, including recruitment of other cells. They are classified into families: CC, CXC and CX3C. CXC chemoattract mainly on neutrophils and CC act mainly on monocytes, eosinophils and mast cells. Mast cells are important cells in the modulation of allergic and inflammatory diseases. Activation of mast cells with specific IgE antibody and antigens or other active compounds such as Substance P and corticotrophin releasing hormone causes transcription and translation of several different cytokines/chemokines such as tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1 (MIP-1) and GM-CSF, RANTES, MCP-1, CXCL8, along with other proinflammatory compounds, proteases (chymase and tryptase), histamine, leukotrienes and prostaglandin D2. Neutralization of chemokines may reduce inflammatory cell accumulation and may protect against allergy, toxic shock syndrome and inflammatory diseases.