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Laura Caruso,1 Alessia Castellino,2 Daniela Dessì,3 Leonardo Flenghi,4 Antonio Giordano,5 Adalberto Ibatici,6 Cesare Massone,7 Alessandro Pileri,8 Ilaria Proietti,9 Livio Pupo,10 Pietro Quaglino,11 Serena Rupoli,12 Pier Luigi Zinzani13,14 1Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco Di Catania, Catania, Italy; 2Department of Hematology, Santa Croce E Carle Hospital, Cuneo, Italy; 3Department of Hematology, Businco Hospital Arnas AOB, Cagliari, Italy; 4Hematology and Bone Marrow Transplantation Unit, Santa Maria Della Misericordia Hospital, Perugia, Italy; 5Department of Hematology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, Italy; 6Hematology and Transplant Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 7Dermatology Unit, Ospedali Galliera, Genova, Italy; 8Dermatology Unit, IRCCS S. Orsola-Malpighi Polyclinic, Bologna, Italy. Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy; 9Dermatology Unit”Daniele Innocenzi”, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Terracina, Italy; 10UOC Lymphoproliferative Diseases, Fondazione PTV Policlinico Tor Vergata, Rome, Italy; 11Dermatologic Clinic, Department of Medical Sciences University of Turin Medical School, Turin, Italy; 12Clinic of Hematology, Ospedali Riuniti Ancona, Ancona, Italy; 13IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; 14Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, ItalyCorrespondence: Pier Luigi Zinzani, IRCCS University Hospital of Bologna, Seràgnoli Institute of Hematology, and Department of Specialized, Diagnostic and Experimental Medicine, University of Bologna, via Massarenti 9, Bologna, 40138, Italy, Tel +39 051 2144042, Fax +39 051 2144037, Email pierluigi.zinzani@unibo.itAbstract: Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients’ symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.Keywords: cutaneous T- cell lymphoma, mycosis fungoides, Sèzary syndrome, mogamulizumab

In this work a proposal of following the point of operation of hydraulic micro-turbines in autonomous operation regime is presented.lt is sought to adjust the operation point automatically to which imposes the demand by means of the combined control of load and flow. Simulation results are presented in Matlab®/Simulink with models obtained through analytic and proven with methods of experimental identification. Lastly, the results of simulation are presented of combining both methods, some performance considerations, limitations and future works. [ABSTRACT FROM AUTHOR]

induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CX 3 CR1 eGFP+/- CCR2 RFP+/- murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation. First, cytokine analysis demonstrates that both bi-partite and tri-partite NSPHs can be triggered to release IL6 and CXCL10 following three days of stimulation with, respectively, TNFα + IL1β + IFNγ and LPS + IFNγ. Additionally, immunocytochemical analysis for G3BP1 and PABPC1 revealed the development of stress granules in both bi-partite and tri-partite NSPHs after 3 days of stimulation. To further investigate the observed signs of inflammatory response and cellular stress, we performed an untargeted transcriptomic and proteomic analysis of bi- and tri-partite NSPHs under steady-state and inflammatory conditions. Here, using the combined differential gene and protein expression profiles between unstimulated and stimulated NSPHs, Ingenuity Pathway Analysis (IPA) confirms the activation of canonical pathways associated with inflammation and cellular stress in both bi-partite and tri-partite NSPHs. Moreover, our multi-omics analysis suggests a higher level of downstream inflammatory responses, impairment of homeostatic and developmental processes, as well as activation of cell death processes in stimulated tri-partite NSPHs compared to bi-partite NSPHs. Concluding, these results emphasise the advantages of including microglia in NSPH research to study inflammation-induced neurodegeneration in a 3D neural environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aggregation of Amyloid- β (A β ) peptides is associated with neurodegeneration in Alzheimer's disease (AD). We previously identified novel naphtalene derivatives, including the lead compound Amylovis-201, able to form thermodynamically stable complexes with A β species, peptides and fibrils. As the drug showed a chemical scaffold coherent for an effective interaction with the σ 1 receptor chaperone and as σ 1 agonists are currently developed as potent neuroprotectants in AD, we investigated the pharmacological action of Amylovis-201 on the σ 1 receptor. We report that Amylovis-201 is a potent σ 1 agonist by several in silico , in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action at σ 1 receptors. Furthermore, we show for the first time that classical σ 1 receptor agonist (PRE-084), and antagonist (NE-100) are able to interact and disaggregate A β 25-35 fibrils. Interestingly, Amylovis-201 was the only compound inhibiting A β 25-35 aggregates formation. Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent and σ 1 receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Alzheimer's disease is the most common neurodegenerative disease, and its treatment is lacking. In this work, we tested Amylovis-201, a naphthalene-derived compound, as a possible therapeutic candidate for the treatment of AD. For this purpose, we performed three experiments. In the first and third experiment, animals received a bilateral administration of streptozotocin and, starting 24 h after injection, a daily dose of Amylovis-201 (orally), for 17 days or for the whole time of the experiment respectively (28 days), after which learning and memory, as well as the number of hippocampal dentate gyrus cells, were assessed. In the second experiment, healthy animals received a single dose of Amylovis-201, 10 min or 5 h after the learning section to assess whether this substance could promote specific mechanisms involved in memory trace formation. Our data show that, administration of a single dose of Amylovis-201, 10 min after the end of training, but not at 5 h, produces a prolongation in memory duration, probably because it modulates specific mechanisms involved in memory trace consolidation. Furthermore, daily administration of Amylovis-201 to animals with bilateral intracerebroventricular injection of STZ produces a reduction in the loss of the hippocampus dentate gyrus cells and an improvement in spatial memory, probably because Amylovis-201 can interact with some of the protein kinases of the insulin signaling cascade, also involved in neural plasticity, and thereby halt or reverse some of the effects of STZ. Taking to account these results, Amylovis-201 is a good candidate for the therapeutic treatment of AD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by a constant accumulation of lipids in the liver. This hepatic lipotoxicity is associated with a dysregulation of the first step in lipid catabolism, known as beta oxidation, which occurs in the mitochondrial matrix. Eventually, this dysregulation will lead to mitochondrial dysfunction. To evaluate the possible involvement of mitochondrial DNA methylation in this lipid metabolic dysfunction, we investigated the functional metabolic effects of mitochondrial overexpression of CpG (MSssI) and GpC (MCviPI) DNA methyltransferases in relation to gene expression and (mito)epigenetic signatures. Overall, the results show that mitochondrial GpC and, to a lesser extent, CpG methylation increase bile acid metabolic gene expression, inducing the onset of cholestasis through mito-nuclear epigenetic reprogramming. Moreover, both increase the expression of metabolic nuclear receptors and thereby induce basal overactivation of mitochondrial respiration. The latter promotes mitochondrial swelling, favoring lipid accumulation and metabolic-stress-induced mitophagy and autophagy stress responses. In conclusion, both mitochondrial GpC and CpG methylation create a metabolically challenging environment that induces mitochondrial dysfunction, which may contribute to the progression of MASLD.

Primary cutaneous CD30+ lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis. The prognosis of the disease is usually excellent but, in a minority of cases, it presents with extracutaneous involvement and aggressive behavior. The case we present-relapsed after surgical excision, immunosuppressive therapy, and conventional chemotherapy-is the first one treated with Autologous Stem Cell transplant followed by Brentuximab Vedotin consolidation, a scheme already used for high risk Hodgkin Lymphoma.

Background: Gastric Diffuse large B-cell lymphoma (DLBCL) is the most common extranodal site of lymphoma's involvement (30%-40% of all extranodal lymphomas and 55%-65% of all gastrointestinal lymphomas). However, gastric localizations are also sometimes found in systemic DLBCL. Gastric complications such as bleeding, perforation, and stenosis under chemotherapy are well documented., Methods: We retrospectively analyzed 15 patients with newly diagnosed DLBCL with gastrointestinal involvement. Endoscopies were performed in these patients before and after treatment. Treatment consisted of cyclophosphamide low-dose pre-phase chemotherapy before conventional-dose chemotherapy., Results: Endoscopy at staging detected ulcers in 12 patients (80%). After low-dose pre-phase chemotherapy, GI ulcers healed in 91.6% of cases (1 ulcer detected). After the whole treatment (Low-dose pre-phase + chemotherapy) 9 patients (60%) achieved complete response, 4 patients (26.6%) partial response, 2 (13,3%) patients presented disease progression. The most frequent adverse event was neutropenia (73.3%); the most frequent non-hematological adverse event was transaminases elevation (20%)., Conclusion: Cyclophosphamide low-dose pre-phase chemotherapy resulted in a safe and effective way to prevent adverse events in systemic DLBCL with gastrointestinal involvement., Competing Interests: Competing interests: The authors declare no conflict of Interest. Compliance with Ethical Standards. Disclosure of potential conflicts of interest: The authors did not receive support from any organization for the submitted work. The authors have no relevant financial or non-financial interests to disclose. Ethics Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study.

Cerebral ischemia constitutes the most frequent type of cerebrovascular disease. The reduction of blood supply to the brain initiates the ischemic cascade starting from ionic imbalance to subsequent glutamate excitotoxicity, neuroinflammation and oxidative stress, eventually causing neuronal death. Previously, the authors have demonstrated the in vitro cytoprotective and antioxidant effects of a new arylidene malonate derivative, KM-34, against oxidizing agents like hydrogen peroxide, glutamate or Fe 3+ /ascorbate. Here, we examined for the first time the neuroprotective effect of KM-34 on ischemia/reperfusion models. In vitro, treatment with 10 and 50 μM KM-34 reduced the cellular death (propidium iodide incorporation) induced by oxygen glucose deprivation (OGD) in rat organotypic hippocampal slices cultures. In vivo, stroke was induced in male Wistar rats through middle cerebral artery occlusion (MCAO), followed by 23 h of reperfusion. KM-34 was orally administered 105 min after MCAO onset. We noticed that 1 mg/kg KM-34 reduced infarct volume and neurological score, and increased the latency to fall in the Hanging Wire test compared to vehicle-treated ischemic animals. While ischemic and sham-operated groups showed similar horizontal locomotor activity, vertical counts decreased after MCAO, suggesting that vertical movements are more sensitive to the ischemic injury. Treatment with KM-34 also alleviated the mitochondrial impairment (ROS generation, swelling and membrane potential dissipation) induced by transient MCAO but not significant alterations were found in oxidative stress parameters. Overall, the study provides preclinical evidences confirming the neuroprotective effects of a novel synthetic molecule and paved the way for future investigations regarding its therapeutic potential against brain ischemia/reperfusion injury., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The association between urticaria and different virus infections has been reported in many studies. Different virus infections have been reported to be comorbidities of spontaneous urticaria. In this paper, we report the case of a male patient with acute urticaria 7 days after he left the hospital where he was treated for coronavirus disease 2019 (COVID-19). This infection may act as a causative or a facilitating factor for the initiation of acute urticaria and additional cofactors such as stress may contribute for the urticaria phenotype to be expressed. Additional facts for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus in future will clarify if urticarial rash is one of the COVID's multiple faces., (© 2020 Wiley Periodicals LLC.)

The aggregation of β-amyloid peptides is associated to neurodegeneration in Alzheimer's disease (AD) patients. Consequently, the inhibition of both oligomerization and fibrillation of β-amyloid peptides is considered a plausible therapeutic approach for AD. Herein, the synthesis of new naphthalene derivatives and their evaluation as anti-β-amyloidogenic agents are presented. Molecular dynamic simulations predicted the formation of thermodynamically stable complexes between the compounds, the Aβ 1-42 peptide and fibrils. In human microglia cells, these compounds inhibited the aggregation of Aβ 1-42 peptide. The lead compound 8 showed a high affinity to amyloid plaques in mice brain ex vivo assays and an adequate log P oct/PBS value. Compound 8 also improved the cognitive function and decreased hippocampal β-amyloid burden in the brain of 3xTg-AD female mice. Altogether, our results suggest that 8 could be a novel therapeutic agent for AD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The complexity of the ischemic cascade is based on the integrated crosstalk of every cell type in the neurovascular unit. Depending on the features of the ischemic insult, several cell death mechanisms are triggered, such as apoptosis, necroptosis, ferroptosis/oxytosis, ETosis or pyroptosis, leading to reactive astrogliosis. However, emerging evidence demonstrates a dual role for the immune system in stroke pathophysiology, where it exerts both detrimental and also beneficial functions. In this review, we discuss the relevance of several cell death modalities and the dual role of the immune system in stroke pathophysiology. We also provide an overview of some emerging immunomodulatory therapeutic strategies, amongst which saponins, which are promising candidates that exert multiple pharmacological effects., (© 2020 The Authors.)

Occasionally, non-Hodgkin lymphomas (NHL) occur simultaneously or subsequently to Hodgkin disease. We report on a case of a woman with Hodgkin lymphoma treated with ABVD, who developed 4 years later T-cell NHL with both nodal and extranodal involvement. Brentuximab vedotin could be an effective choice in treating metachronous T-cell NHL., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

In solid tumors and lymphomas, the neutrophil/lymphocyte (N/L) ratio at diagnosis has been shown to be a prognostic factor. The aim of our study was to validate the originally reported N/L ratio cut-point of 3.5 in patients with diffuse large B-cell lymphoma (DLBCL) registered in an Italian real-life database. The prognostic role of the N/L ratio at diagnosis on event-free survival (EFS) and overall survival (OS) was assessed in 505 patients with DLBCL. Patients with an N/L ratio <3.5 ( n  = 249) had a 4-year EFS probability of 76% and OS probability of 86%, significantly higher than the 4 year EFS rate of 48% and OS rate of 64% in patients with N/L ratio ≥3.5 ( n  = 256, both p <.0001). The N/L ratio was an independent prognostic factor in the multivariate analysis including the IPI score, and could separate patients with a low/intermediate risk IPI (IPI <3).

Primary cutaneous anaplastic large cell lymphoma is a CD-30 positive lymphoproliferative disorder with good prognosis, usually treated with radiation therapy and surgery. Head, neck, and extremities are the most frequently involved sites. In this paper, we describe an unusual case of oral localization, recurring after skin-involving radiotherapy, successfully treated with sixteen cycles of brentuximab vedotin. This could be a more effective approach with a less detrimental toll for treating these rare disorders., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Federico Meconi et al.)

Background: Human herpes virus 8 (HHV8) is the causative agent of Kaposi's sarcoma and has been associated with an increasing number of hematologic diseases such as primary effusion lymphoma (PEL) (both classic and extracavitary form), multicentric Castleman disease and the germinotropic lymphoproliferative disorder. PEL is a rare B cell non-Hodgkin lymphoma that primarily affects immunocompromised patients; aggressive chemotherapy and antiretroviral therapy (ART) with protease inhibitors have been used, with poor results. We present a case of extracavitary PEL in an HIV-infected patient, regressed after ART initiation., Case Presentation: A 42-year-old male was admitted to the emergency room because of several months of malaise, fever and progressive deterioration of the general conditions. On physical examination soft non-painful subcutaneous masses were palpable at retronuchal, retroauricolar and thoracic regions. HIV serology resulted positive: HIV plasma viremia was 782,270 copies/mL, CD4 103 cells/mL. The excision of one of the masses, metabolically active at a positron emission tomography (PET-CT) scan, revealed an HHV8-related extracavitary PEL. HHV8 plasma viremia was 44,826 copies/mL. ART with tenofovir alafenamide/emtricitabine/dolutegravir was started together with ganciclovir for cytomegalovirus chorioretinitis. The progressive disappearance of the masses was seen after 6 weeks of ART, and a PET-CT scan resulted completely negative at 3 months. After 19 months of ART the patient was in remission of PEL, HIV viremia was undetectable (< 20 copies/mL), CD4 count was 766 cells/mL and HHV8 viremia was undetectable., Conclusions: In this clinical case, the complete regression of PEL has been achieved after the immune recovery, as a consequence of ART introduction, without chemotherapy. It cannot be excluded that ganciclovir, used for the treatment of CMV chorioretinitis, may have contributed to the control of HHV8 replication. Whether to try or not a conservative approach in HIV-infected PEL patients must be carefully evaluated, considering the patient's characteristics and the prognostic factors.

Competing Interests: Competing interests: The authors have declared that no competing interests exist.

We report on a case of Sweet's syndrome associated with multiple myeloma, as harbinger for disease relapse.

Stroke represents one of the first causes of mortality and morbidity worldwide. We evaluated the therapeutic potential of a novel semi-synthetic spirosteroid sapogenin derivative "S15" in a transient middle cerebral artery occlusion (tMCAO) focal ischemia model in rat. S15-treated rats had significantly reduced infarct volumes and improved neurological functions at 24h post-reperfusion, compared with ischemia. Corresponding gene expression changes in brain were characterized by mRNA sequencing and qPCR approaches. Next, we applied geneset, pathway and transcription factor motif enrichment analysis to identify relevant signaling networks responsible for neuronal damage upon ischemia-reperfusion or neuroprotection upon pretreatment with S15. As expected, ischemia-reperfusion brain damage strongly modulates transcriptional programs associated with immune responses, increased differentiation of immune cells as well as reduced (cat)ion transport and synaptic activity. Interestingly, S15-dependent neuroprotection regulates inflammation-associated genes involved in phagosome specific resolution of tissue damage, chemotaxis and anti-inflammatory alternative activation of microglia. Altogether our transcriptome wide RNA sequencing and integrated pathway analysis provides new clues in the neuroprotective properties of a novel spirosteroid S15 or neuronal damage in rat brains subjected to ischemia, which opens new perspectives for successful treatment of stroke., (Copyright © 2017. Published by Elsevier Inc.)

Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro anti-excitotoxic and anti-inflammatory activities of natural and endogenous steroids. Our results show that the plant-derived steroid solasodine decreased PC12 glutamate-induced excitotoxicity, but not the cell death induced by mitochondrial damage and glucose deprivation. Among the two synthetic spirosteroid analogues, only the (25R)-5α-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1β by stimulated primary microglia. These findings provide further insights into the role of specific modifications of the A and B rings of sapogenins for their neuroprotective potential.

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib., (Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.)

The efficacy and safety of two polyvalent horse-derived antivenoms in Bothrops asper envenomings were tested in a randomized, double-blind, clinical trial performed in Colombia. Both antivenoms were manufactured from the same pool of hyperimmune plasma. Antivenom A was made of F(ab')2 fragments, generated by pepsin digestion and caprylic acid precipitation, whereas antivenom B consisted of whole IgG molecules produced by caprylic acid precipitation followed by ion-exchange chromatography. Besides the different nature of the active substance, antivenom B had higher protein concentration, slightly higher turbidity and aggregate content. No significant differences were observed in the efficacy of antivenoms. Both halted local and systemic bleeding (P = 0.40) within 6-12 h of treatment in 100% of the cases, and restored blood coagulation (P = 0.87) within 6-24 h in 84.7% of patients, and within 48 h in all of them, in agreement with restoration of plasma fibrinogen concentration. Venom concentrations in serum dropped significantly (P < 0.001), to very low levels, 1 h after antivenom infusion. Nevertheless, eight patients (11.1%), four for each antivenom, presented recurrence of venom antigenaemia at different times, from 6 to 96 h, with clinical significance (recurrent coagulopathy) only in one group B patient (2.9%). Serum creatine kinase (CK) activity was increased, as a consequence of local myonecrosis. There was no significant difference (P = 0.51) in the incidence of early adverse reactions to antivenom administration (28.9% for patients of group A and 20.6% for patients of group B), most of the reactions being mild, mainly cutaneous. The most frequent complications were cellulitis (16.7%), abscess formation (5.6%), acute renal failure (8.3%), and compartmental syndrome (5.6%). In conclusion, IgG and F(ab')2 antivenoms, prepared by caprylic acid fractionation, presented similar efficacy and safety profiles for the treatment of B. asper envenomings in Colombia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with several reported pharmacological actions. We have assessed the protective action of GA on iron-induced neuronal cell damage by employing the PC12 cell line and primary culture of rat cortical neurons (PCRCN). A strong protection by GA, assessed by the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbox-anilide (XTT) assay, was revealed, with IC(50) values <1 µM. GA also inhibited Fe(3+)-ascorbate reduction, iron-induced oxidative degradation of 2-deoxiribose, and iron-induced lipid peroxidation in rat brain homogenate, as well as stimulated oxygen consumption by Fe(2+) autoxidation. Absorption spectra and cyclic voltammograms of GA-Fe(2+)/Fe(3+) complexes suggest the formation of a transient charge transfer complex between Fe(2+) and GA, accelerating Fe(2+) oxidation. The more stable Fe(3+) complex with GA would be unable to participate in Fenton-Haber Weiss-type reactions and the propagation phase of lipid peroxidation. The results show a potential of GA against neuronal diseases associated with iron-induced oxidative stress.

Objective: A review of current foundations for the medical diagnosis of vasospam and delayed cerebral ischaemia due to spontaneous subarachnoid haemorrhage., Development: A review of available tests for the investigation of vasospasm (transcraneal Doppler, angiographic methods) and delayed cerebral ischaemia (clinical exam, computerised tomography by X rays, magnetic resonance, emission computerised tomography, electroencephalography, microdialysis) based on type and quality of information, advantages and limitations. Grading and trends for application were also considered for differential diagnosis., Conclusions: In current clinical practice the most advisable guideline for screening and diagnosis monitoring of vasospasm and delayed cerebral ischaemia is in the first place, based on clinical examination and transcraneal Doppler. The electroencephalographic monitoring, computerised tomography techniques and multi-modal magnetic resonance are justified in specific situations. Digital subtraction angiography is the current gold standard for diagnosis of cerebral vasospasm. There is a need for more and higher quality articles about the utility of diagnostic tests in this context.

Aims: The purpose of this work is to focus on the main practical aspects of the techniques used for the neurological physical examination of the sensory functions and to present an approach for the practice of this study., Development: Despite the difficulty often involved in interpreting its results, today the formal examination of sensation is still an important part of a complete neurological evaluation and remains valid in the search for a correct diagnosis and suitable treatment. We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for abnormalities in the sensory functions. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. We present a detailed review of the practical aspects of the main techniques used in the physical examination of this neurological category. In addition to the tests used to examine the peripheral and cortical sensory systems, we also describe other techniques designed to trigger pain or other sensory symptoms due to radicular lesions or injury to the median nerve., Conclusions: We present a detailed description of the main clinical techniques used in the neurological physical examination of the sensory functions, as well as an approach that allows them to be performed on adult patients. In addition, we underline the importance of physically examining the sensory functions in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

Aims: The aim of this study is to highlight the chief practical aspects of the techniques used in the neurological physical examination of the motor and reflex functions., Development: We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for abnormalities in the motor and reflex functions of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. We present a detailed review of the practical aspects of the main techniques used in the physical examination of these neurological categories. The motor function is explored using techniques that examine muscle tone, muscle strength, muscle fatigability, hypokinesia, tremor, coordination and gait. Lastly, in this category several manoeuvres that are useful in hysterical or mimicking paralyses are also dealt with. Reflexes to examination are usually divided into: 1. Myotatic reflexes; 2. Cutaneomucous reflexes; 3. Spinal cord or defence automatism reflexes; 4. Posture and attitude reflexes. We also add the study of primitive pathological reflexes, remote reflexes, synkinesias and signs of meningeal irritation., Conclusions: We present a detailed description of the main clinical techniques used in the neurological physical examination of motility and reflexes, as well as an approach that allows them to be performed on adult patients. In addition, we underline the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

Aims: The purpose of this work is to focus on the main practical aspects of the techniques used for the physical examination of the nervous system and to present an approach for the practice of this study in adult patients., Development: We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for alterations in the functioning of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. The techniques and data from this examination are organised into five broad categories: mental status, cranial nerves, motor function, reflex function and sensory function. The practical aspects of the main techniques used in the physical exploration are reviewed and we also describe the technique to be employed for palpating the main peripheral nerves., Conclusions: The study offers a detailed description of the chief clinical techniques used in the physical exploration of the cranial nerves and for the palpation of the peripheral nerves; we also present an approach to performing the neurological examination. Furthermore, we highlight the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

Aims: The aim of this paper is to offer a reflection on the principles used to define a syndromic entity and for the evaluation of its manifestations and the aetiopathogenesis., Method: First, the paper looks at several of the different definitions of syndrome available and examines which are the essential features for this term to be employed in a clinical entity. The topographical and semiological perspectives are then dealt with, so as to be able to sort clinical syndromes and charts are used to offer representative examples. The main deficiencies in the use of terms to describe syndromes and the possible causes of such situations are also investigated. Following that, the chief semiological aspects in the diagnosis of a syndrome are assessed. Emphasis is placed on the factors that influence the variability of clinical behaviour, on the factors that come to bear on the recognition of the manifestations using the research methods available to us, on the rule of iterative confirmation of the symptom and on the characterisation and coordination of the symptom with other related phenomena. Lastly, the aetiopathological foundations of clinical syndromes are evaluated. We highlight the importance of determining the underlying anatomofunctional disorder, the classical distinctions concerning this, and the relation between syndrome and disease. The diagnostic criteria from numerous neurological syndromes are used as examples., Conclusions: The concept of syndrome has been defined in an attempt to illustrate the presence of inappropriate, incorrect terms with adverse repercussions in the theoretical and practical areas. We also propose ways of resolving the faults found.