Failure Of Conventional Treatments Research Articles

The Mechanisms of Immune Evasion in Cancer Stem Cells and Related Immunotherapy Advances

Cancer Stem Cells (CSCs), as a unique subset of tumor cells, play a crucial role in tumor initiation, progression, and recurrence due to their self-renewal and differentiation capabilities. CSCs exhibit significant immune evasion abilities, allowing them to escape host immune surveillance, leading to the failure of conventional treatments. This paper reviews the definition, characteristics, and immune evasion mechanisms of CSCs, including immune checkpoint pathways, immunosuppressive microenvironment, and changes in surface antigen expression. Additionally, it explores various immunotherapies targeting CSCs, such as immune checkpoint inhibitors, CAR-T cell therapy, tumor vaccines, and other emerging therapies, discussing their research progress and clinical application prospects. By comprehensively understanding the immune evasion mechanisms of CSCs and related immunotherapies, we aim to provide new insights and strategies for future cancer treatments.

Recent Biochemical Advances in Antitubercular Drugs: Challenges and Future.

Tuberculosis (TB) is one of the leading causes of death world-wide after AIDS. It infects around one-third of global population and approximately two million people die annually from this disease because it is a very contagious disease spread by Mycobacterium tuberculosis. The increasing number of drug-resistant strains and the failure of conventional treatments against this strain are the challenges of the coming decades. New therapeutic techniques aim to confirm cure without deterioration, to reduce deaths, contagions and the formation of drug-resistant strains. A plethora of new diagnostic tests are available to diagnose the active tuberculosis, screen latent M. tuberculosis infection, and to identify drug-resistant strains of M. tuberculosis. When effective prevention strategies do not prevail, high rates of early case detection and successive cures to control TB emergence would not be possible. In this review, we discussed the structural features of M. tuberculosis, Multi drug resistance tuberculosis (MDR-TB), extremely drug-resistant tuberculosis (XDR-TB), the mechanism of M. tuberculosis infection, the mode of action of first and second-line antitubercular drugs, the mechanism of resistance to the existing drugs, compounds in preclinical and clinical trial and drugs presently available for the treatment of tuberculosis. Moreover, the new diagnostic techniques to detect M. tuberculosis are also discussed in this review.

Alternative therapeutics to control antimicrobial resistance: a general perspective

Antimicrobial Resistance (AMR) is a critical global health challenge, and in this review article, we examine the limitations of traditional therapeutic methods and the emerging role of alternative therapies. By examining the reasons behind the failure of conventional treatments, including the inadequacy of one-drug-one-enzyme approaches, the complex evolution of AMR, and the impact of drug biotransformation, we better understand why conventional treatments failed. Moreover, the review discusses several alternative therapies, including RNA-based treatments, aptamers, peptide-based therapies, phage therapy, and probiotics, discussing their applications, advantages, and limitations. Additionally, we discuss the obstacles to develop these therapies, including funding shortages, regulatory barriers, and public perception. This comprehensive analysis aims to provide insight into the future of AMR, emphasizing the need for innovative strategies and practical approaches.

Urolithin B protects mice from diet-induced obesity, insulin resistance, and intestinal inflammation by regulating gut microbiota composition.

The increasing prevalence of obesity and type 2 diabetes (T2D) signifies the failure of conventional treatments for these diseases. The gut microbiota has been proposed as a key player in the pathophysiology of diet-induced T2D. Urolithin B (Uro B), a gut microbiota-derived polyphenol metabolite, exerts several beneficial health effects. In this study, we investigated the metabolic effects of Uro B on high-fat/high-sucrose (HFHS)-fed mice and determined whether its antidiabetic effects are related to the modulation of the gut microbiota. C57BL/6J mice were fed either a chow or HFHS diet. HFHS-fed mice were administered daily with either a vehicle (water) or different doses of Uro B (100 or 200 mg kg-1) for eight weeks. The composition of the gut microbiota was assessed by 16S rRNA sequencing. The results showed that Uro B treatment reduced HFHS-induced weight gain and visceral obesity and decreased liver weight and triglyceride accumulation associated with blunted hepatic oxidative stress and inflammation. Furthermore, Uro B administration improved insulin sensitivity as revealed by improved insulin tolerance, a lower homeostasis model assessment of insulin resistance, and decreased glucose-induced hyperinsulinemia during the oral glucose tolerance test. Uro B treatment was found to lower the intestinal triglyceride content and alleviate intestinal inflammation and oxidative stress. Remarkably, Uro B treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in metagenomic samples. In conclusion, Uro B exerts beneficial metabolic effects by alleviating HFHS diet-induced features of metabolic syndrome, which is associated with a proportional increase in the population of Akkermansia spp.

Metal doped silica nanohybrids with extensive bacterial coverage for antibacterial applications exhibit synergistic activity

Nanotechnology has triumphantly overcome several barriers that have formed in modern life. Bacterial infections are a critical public health issue. They emphasized the failure of conventional treatments, high mortality and morbidity rates, antibiotic resistance, and other factors leading to the development of novel and affordable antibacterial medications. In this study, three types of metals (Ag, Cu, and Co) were doped separately into a silanol network in silica nanoparticles. The synthesized monometallic nanohybrids were combined in equal proportions to formulate bi and trimetallic nanohybrids. They were characterized structurally and morphologically. Fourier transform infrared (FTIR) and Raman spectroscopy studies were used to investigate the formation of the bonds and the pertinent peak positions. X-ray diffractograms (XRD) validated the crystalline structures of the metal nanohybrids. X-ray photoelectron spectroscopic study (XPS) confirmed the successful addition of metals to the silanol network. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images were used to characterize the morphology of nanohybrids and demonstrate their dimensions are on the nanoscale. The fraction of each metal doped in the silanol network was determined using energy dispersive spectroscopy (EDS) and atomic absorption spectrometry (AAS). To assess activity and confirm antibacterial synergy, the antibacterial activity of all synthesized nanohybrids was examined. The minimum inhibitory concentration-MIC (Ranged from 12.25 to 1560.00 μg/mL), minimum bactericidal concentration-MBC (Ranged from 197.00 to 3125.00 μg/mL), IC50 values (Ranged from 30.56 to 1683.00 μg/mL-) and fractional inhibitory concentration index (FICI) were determined and compared. Well diffusion assay was conducted against both ATCC cultures and clinical samples of gram-positive bacteria; Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), MRSA (ATCC 33591) and gram-negative bacteria; Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC BAA 1706) and Pseudomonas aeruginosa (ATCC 27853). The highest synergistic radical scavenging performance of trimetallic nanohybrid (90.67 ± 0.095 %) was established by the DPPH (2,2 diphenyl-1-picrylhydrazil) experiment. Finally, when compared to monometallic nanohybrids, it was demonstrated that the synthesized multimetallic nanohybrids have a substantial potential as an emerging and cost-effective antibacterial agent.

Frequent expression of CD45RO memory T cell marker as well as low to high expression of PD-1 and PD-L1 inhibitory molecules in seminoma and dysgerminoma

BackgroundSeminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment. According to the failure of conventional treatments in some patients, it is crucial to identify novel prognostic and therapeutic biomarkers for these patients. The objectives of this study were to evaluate the expression of CD45RO and PD-1/PD-L1 and investigate their association with the clinicopathological characteristics of the patients. MethodsImmunohistochemistry was performed to assess the expression of CD45RO, PD-1, and PD-L1 in tumor-infiltrated lymphocytes (TILs), and tumor cells in 33 seminoma and 31 dysgerminoma patients. The expression levels were evaluated using a semiquantitative approach, weighted histoscore, which considers both the intensity and extent of staining. ResultsAll seminoma and dysgerminoma patients exhibited CD45RO expression in TILs, with 66.7 % and 90.3 % displaying high levels of expression, respectively. PD-1 expression in TILs was observed at low levels in 81.8 % and 77.4 % and at high levels in 18.2 % and 19.4 % of seminoma and dysgerminoma patients, respectively. Likewise, low expression of PD-L1 in tumor cells was detected in 63.6 % of seminoma and 61.3 % of dysgerminoma patients, while none of the patients exhibited high expression of PD-L1. In seminoma patients, a positive correlation was observed between PD-1 expression in TILs and CD45RO expression and between PD-L1 expression in tumor cells and TILs score. ConclusionThe frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.

Population Pharmacodynamic Modelling of the CD19+ Suppression Effects of Rituximab in Paediatric Patients with Neurological and Autoimmune Diseases.

Limited pharmacotherapy and the failure of conventional treatments in complex pathologies in children lead to increased off-label use of rituximab. We aimed to characterize the time course of CD19+ B lymphocytes (CD19+) under treatment with intravenous rituximab in children with neurologic and autoimmune diseases and to evaluate the impact of covariates (i.e., demographics, diagnosis and substitution between innovator and biosimilar product) on rituximab pharmacodynamics and disease activity. Pre- and post-drug infusion CD19+ in peripheral blood were prospectively registered. A population pharmacodynamic model describing the time course of CD19+ was developed with NONMEM v7.4. Simulations of three different rituximab regimens were performed to assess the impact on CD19+. Logistic regression analysis was performed to identify predictors of clinical response recorded through disease activity scores. 281 measurements of CD19+ lymphocyte counts obtained from 63 children with neurologic (n = 36) and autoimmune (n = 27) diseases were available. The time course of CD19+ was described with a turn-over model in which the balance between synthesis and degradation rates is disrupted by rituximab, increasing the latter process. The model predicts half-lives (percent coefficient of variation, CV(%)) of rituximab and CD19+ of 11.6 days (17%) and 173.3 days (22%), respectively. No statistically significant effect was found between any of the studied covariates and model parameters (p > 0.05). Simulations of different regimens showed no clinically significant differences in terms of CD19+ repopulation times. A trend towards a lack of clinical response was observed in patients with lower CD19+ repopulation times and higher areas under the CD19+ versus time curve. Rituximab pharmacodynamics was described in a real-world setting in children suffering from autoimmune and neurologic diseases. Diagnosis, substitution between innovator rituximab and its biosimilars or type of regimen did not affect rituximab-induced depletion of CD19+ nor the clinical response in this cohort of patients. According to this study, rituximab frequency and dosage may be chosen based on clinical convenience or safety reasons without affecting CD19+ repopulation times. Further studies in larger populations are required to confirm these results.

Update on Treatment of Enteric Fever in Pediatric Patients According to Current Multidrug Resistance

Introduction: Enteric fever is a severe systemic disease caused by a gram-negative bacillus, Salmonella Enterica serotype Typhi. It commonly occurs in children and young adults. The aim of the research is to address the treatment of enteric fever in pediatric patients including multidrug resistance to first-line drugs. The treatment of enteric fever has been complicated by the worldwide spread of typhoid organisms resistant to ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol. Ceftriaxone damages the germ structure that can kill Salmonella typhi, germ resistance is limited and there are no harmful side effects when administered to children. Discussion: The interest in this pathogen is based on Salmonella typhi strains that have become multiresistant to antibiotics such as some cephalosporins, fluoroquinolones, etc. The importance in terms of antimicrobial resistance lies in the failure of conventional treatments, which causes a delay in effective therapeutic management. Conclusion: Cephalosporins are currently the first line against enteric fever, specifically ceftriaxone and cefixime. In order for the treatment to conclude satisfactorily, it is necessary to observe the disappearance of fever and the decrease of accompanying symptoms.

Seaweed Extracts as an Effective Gateway in the Search for Novel Antibiofilm Agents against Staphylococcus aureus.

Treatment of biofilm-associated infections has become a major challenge in biomedical and clinical fields due to the failure of conventional treatments in controlling this highly complex and tolerant structure. Therefore, the search for novel antibiofilm agents with increased efficacy as those provided by natural products, presents an urgent need. The aim of this study was to explore extracts derived from three algae (green Ulva lactuca, brown Stypocaulon scoparium, red Pterocladiella capillacea) for their potential antibiofilm activity against Staphylococcus aureus, bacterium responsible for several acute and chronic infections. Seaweed extracts were prepared by successive maceration in various solvents (cyclohexane (CH), dichloromethane (DCM), ethyl acetate (EA), and methanol (MeOH)). The ability of the different extracts to inhibit S. aureus biofilm formation was assessed using colony-forming unit (CFU) counts method supported by epifluorescence microscopic analysis. Effects of active extracts on the biofilm growth cycle, as well as on S. aureus surface hydrophobicity were evaluated. Results revealed the ability of four extracts to significantly inhibit S. aureus biofilm formation. These findings were supported by microscopy analyses. The gradual increase in the number of adherent bacteria when the selected extracts were added at various times (t0, t2h, t4h, t6h, and t24h) revealed their potential effect on the initial adhesion and proliferation stages of S. aureus biofilm development. Interestingly, a significant reduction in the surface hydrophobicity of S. aureus treated with dichloromethane (DCM) extract derived from U. lactuca was demonstrated. These findings present new insights into the exploration of seaweeds as a valuable source of antibiofilm agents with preventive effect by inhibiting and/or delaying biofilm formation.

The role of hyperbaric oxygen therapy in the treatment of radiation lesions.

Cancer remains one of the leading causes of death worldwide, with 50-60% of patients requiring radiotherapy during the course of treatment. Patients' survival rate has increased significantly, with an inevitable increase in the number of patients experiencing side effects from cancer therapy. One such effect is late radiation injuries in which hyperbaric oxygen therapy appears as complementary treatment. With this work we intend to divulge the results of applying hyperbaric oxygen therapy among patients presenting radiation lesions in our Hyperbaric Medicine Unit. Retrospective analysis of clinical records of patients with radiation lesions treated at the Hyperbaric Medicine Unit assessed by the scale Late Effects of Normal Tissues-Subjective, Objective, Management, Analytical (LENT-SOMA) before and after treatment, between October 2014 and September 2019 were included. Demographic characteristics, primary tumor site, subjective assessment of the LENT-SOMA scale before and after treatment were collected and a comparative analysis (Students t test) was done. 88 patients included: 33 with radiation cystitis, 20 with radiation proctitis, 13 with osteoradionecrosis of the mandible and 22 with radiation enteritis. In all groups, there was a significant decrease (p < 0.005) in the subjective parameter of the LENT-SOMA scale. Late radiation lesions have a major influence on patients' quality of life. In our study hyperbaric oxygen therapy presents as an effective therapy after the failure of conventional treatments. Hyperbaric oxygen therapy is an effective complementary therapy in the treatment of refractory radiation lesions.

Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Cutis Verticis Gyrata: Case Report and Review of Literature

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare disease clinically characterized by a wide range of cutaneous and osteoarticular manifestations. Here, we report a case of SAPHO syndrome with cutis verticis gyrata (CVG) and investigated the genetic causes in the four members of this pedigree. After failure of conventional treatments, a recombinant human TNF-α receptor II:IgG Fc fusion protein (rhTNFR:Fc, YISAIPU®) achieved good control of the disease at the 2-year follow-up. We did not identify any pathogenic mutation in this pedigree. We also summarized the clinical and therapeutic characteristics of 83 patients with SAPHO syndrome through the China National Knowledge Infrastructure (CKNI) database from 2016 to 2021. Patients with acne were young and predominantly male. About 45.8% patients were treated with biological therapies or traditional Chinese medicine (TCM), 84.2% of which showed positive effects against cutaneous and osteoarticular manifestations. We report a case of SAPHO syndrome with CVG that was successfully treated with rhTNFR:Fc. Our results reveal the genetic heterogeneity involved. Biologics and TCM are likely alternative options for the treatment of SAPHO syndrome.

Current and Future Approaches in Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies.

Chronic spontaneous urticaria (CSU) considerably alters patients’ quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms “anti-IgE antibodies”, “omalizumab”, “ligelizumab”, and “chronic spontaneous urticaria”. The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients’ quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.

Biologic therapy in relapsing polychondritis: navigating between options

Introduction Relapsing polychondritis (RP) is a rare systemic inflammatory disease of unknown etiology, primarily affecting cartilaginous tissue and proteoglycan-rich structures. Clinical manifestations vary from mild symptoms to occasional organ or life-threatening complications. Treatment can be challenging and is mostly based on experience or case reports/series. Areas covered There is growing literature investigating the role of biologics in the management of RP. TNFα antagonists, abatacept, tocilizumab, rituximab, anakinra and tofacitinib have been prescribed in several RP patients, mainly as second-line treatment, after conventional immunosuppressive agents’ failure. Expert opinion : Glucocorticoids represent the gold standard treatment of RP. Conventional immunosuppressants should be administered in refractory patients or when a glucocorticoid-sparing effect is needed. Biologic therapy should be used after failure of conventional treatments or in severe manifestations. TNFα inhibitors are the most prescribed biologic agent, with partial or complete response in several cases; but loss of efficacy may occur over time. Infliximab and adalimumab should be preferred among TNFα antagonists. Abatacept and tocilizumab proved to be effective as second-line biologic agents, but frequent infections are reported with the former. Data on anakinra and rituximab are controversial, therefore they are not recommended as first-line biologic drugs. The use of JAK inhibitors is still anecdotal.

Intracoronary epinephrine versus adenosine in the management of refractory no-reflow phenomenon: a single-center retrospective cohort study.

BACKGROUND: The no-reflow phenomenon is associated with a considerable reduction in myocardial salvage in patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous intervention (PCI). There has been no head-to-head comparison of intra-coronary epinephrine to adenosine in the management of no-reflow phenomenon.OBJECTIVES: Evaluate the short- and long-term efficacy and safety of using intracoronary epinephrine versus adenosine for management of the catastrophic no-reflow phenomenon that may occur during primary PCI.DESIGN: Retrospective cohort.SETTING: Single center in Egypt.PATIENTS AND METHODS: The study included STEMI patients who developed refractory no-reflow phenomenon during primary PCI after failure of conventional treatments and received either intracoronary epinephrine or adenosine.MAIN OUTCOME MEASURES: No-reflow management measured through improvement of thrombolysis in myocardial infarction grade (TIMI flow), myocardial blush grade, TIMI frame count and major adverse cardiovascular events (MACE) at 1-year follow up.SAMPLE SIZE: 156 patients with refractory no-reflow phenomenon during primary PCI.RESULTS: Successful reperfusion was achieved in 74 of 81 (91.4%) of patients who received epinephrine and in 65 of 75 (86.7%) who received adenosine (P<.05). Fifty-six of 81 patients (69.1%) achieved TIMI III flow after epinephrine administration versus 39 of 75 patients (52.7%) in the adenosine group (P=.04). The incidence of heart failure after 1 year of follow up was lower in the epinephrine group compared to the adenosine group (6.3% vs. 19.2%, P<.017). MACE after 1 year of follow up was lower in patients who received epinephrine compared to those who received adenosine (11.3 % Vs. 26.7 %, P<.01).CONCLUSION: During primary PCI, intracoronary epinephrine is as effective as adenosine in successful management of refractory no-reflow phenomenon with a more favorable long-term prognosis compared to adenosine.LIMITATIONS: Retrospective design.CONFLICT OF INTEREST: None.

Refractory folliculitis decalvans treated with adalimumab: A case series of 23 patients

Refractory folliculitis decalvans treated with adalimumab: A case series of 23 patients

DOP36 Efficacy and safety of vedolizumab in patients with chronic active pouchitis refractory to anti-TNF therapy: Results of a retrospective multicenter study

Abstract Background Total coloproctectomy with ileoanal anastomosis (IAA) is the procedure of choice for patients with treatment-resistant ulcerative colitis (UC). It is most often curative, but can be complicated by pouchitis in 30% of cases, which becomes chronic in 10% of patients. Its treatment is not codified after failure of conventional treatments and a first line of anti-TNF. The objective of our study was to determine the efficacy and safety of vedolizumab (VDZ) in patients with anti-TNF refractory chronic pouchitis. Methods This was a retrospective, multicenter study conducted in 17 hospital centers. Patients were selected from July 2019 to January 2021. All patients had chronic pouchitis refractory to a first line of anti-TNF. We evaluated clinical, endoscopic and biological characteristics at initiation of VDZ therapy, at week (W) 10 as well as at W52. The primary objective of the study was to assess clinical response (improvement ≥ 50% in stool frequency and rectal bleeding) at W52. Secondary objectives were to assess clinical response and remission (absence of symptom) at W10, endoscopic response (improvement ≥ 50% of endoscopic lesions) and remission (mucosal healing) at W10 and 52. Adverse events were also collected. Results Forty-nine patients were included in the study (23 women, 26 men, mean age 48 years). Thirty-one patients (63%) had received only one line of biologic. Forty-four (90%) patients had endoscopic evaluation before initiation of VDZ, and 25 (51%) patients at W10 and 52. CRP was assessed in all patients at baseline, 43 (88%) patients at W10, and 33 (67%) patients at W52.At W10, 17 (34%) patients were clinically responders without corticosteroids, of whom 3 (6%) were in remission; among the 25 patients evaluated, endoscopic response was obtanine in 5 (20%) patients and endoscopic remission in 11 (44%) patients. At W52, 22 (44%) patients were clinically responders, 12 (24%) of whom were in remission; endoscopic response was obtained in 15 (60%) patients and endoscopic remission in 5 (20%) patients. Although there was a trend for CRP to decrease during follow-up (17.3 mg/L at inclusion vs. 7.9 mg/L at W52) in the responder group, there was no significant difference between this subgroup and the non-responder patients at W52. Eight patients (16%) had adverse events, leading to discontinuation of treatment in three of them. Optimization of VDZ at W10 was the only factor predicting nonresponse at W52: 40% in the non-responder group vs 8% in the responder group (p=0.05). At 1 year, 69% of patients were continuing treatment. Conclusion This retrospective multicenter study shows that VDZ is a therapeutic option that may be considered in the treatment of chronic pouchitis refractory to anti-TNF.

Ten-year experience with multidisciplinary diagnosis and treatment of odontogenic sinusitis.

Odontogenic sinusitis is an underdiagnosed entity and is one cause of failure of conventional treatments of sinusitis. Unfortunately, there is no consensus so far on the best management protocol. This retrospective study aimed to suggest a practical management protocol that can reduce misdiagnosis and improve treatment outcomes. The study included 74 patients with confirmed odontogenic sinusitis who were diagnosed and treated over 10 years (2010-2019). The patient data were recorded and analysed. Dental pain was reported in only 31.1 per cent of patients. Fifty-six patients (75.7 per cent) had received dental treatment during the last year, but only 13 (23.1 per cent) reported it. Dental pathology was missed on initial computed tomography evaluation in 24 patients (32.4 per cent). Forty-one patients (55.4 per cent) were successfully treated by dental procedures and antibiotics. Fourteen patients needed functional endoscopic sinus surgery in addition to dental procedures. Successful management of odontogenic sinusitis requires good communication between rhinologists, radiologists and dentists. Dental treatment should be the logical first step in the treatment protocol, unless otherwise indicated.

Intractable spasm in a hypoplastic brachioradial artery during coronary angiography. A last chance before surgery

For the past several years coronary angiography through radial artery has been preferred vascular access over femoral artery due to the favorable outcomes. However radial access has also rare drawbacks. One of the main complications of radial approach is vascular spasm. Although radial spasm can easily be resolved with various intervention, rarely it may be intractable in particular anatomic variations. These patients might be needed advanced treatment methods to overcome vasospasm. In this paper we report an intractable spasm in a hypoplastic radial artery during angiography which could only be resolved by neuraxial blockage after failure of conventional treatments.

Improved Traditional Drugs: State of knowledge for the sustainable management of gastrointestinal parasitic nematodes of small ruminants

This article aims to present the current state of the fight against gastrointestinal parasites in small ruminants from Improved Traditional Drugs (DTI). A host of scientific documents were consulted by means of search engines to gather the information useful for this synthesis. The failure of conventional treatments has led to the use of new methods to treat digestive pathologies due to internal parasitism in herds of sheep and goats. These include, among others, herbal medicine, homeopathy, aromatherapy, the mixed grazing system for small and large ruminants, ... All plant parts of plants can be used in the preparation of remedies. Several scientific studies show that plants are full of chemical compounds that cause anthelmintic effects on gastrointestinal parasites in small ruminants. Literature searches have revealed that studies on DTIs in the management of gastrointestinal nematodes in small ruminants are non-existent. In addition to the forms (decocted, macerated, infused, etc.) traditionally used by breeders, there are other forms that can be used to make DTIs from plant extracts. There are capsules, capsules, tablets etc. The placing on the market of DTIs requires official authorization based on the safety and reproducibility of the products. From the documents consulted, it appears that scientific research has not yet focused on the formulation of DTIs for the treatment of gastrointestinal parasitic nematodes in small ruminants. It will be useful to manufacture them to facilitate access to veterinary care and the sustainable management of animal health.&#x0D; Keywords: Improved Traditional Drugs; Gastrointestinal nematodes; Small ruminants, West Africa; Central Africa.

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials.