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European Journal of Histochemistry : EJH Oct 2023Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties...
Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes. Two interesting candidates are ozone, administered at low doses as gaseous oxygen-ozone mixtures, and procaine. In the present study, we investigated the effects induced on platelets by the in vitro treatment of PRP with ozone or procaine, or both. We combined transmission electron microscopy to obtain information on platelet modifications and bioanalytical assays to quantify the secreted factors. The results demonstrate that, although platelets were already activated by the procedure to prepare PRP, both ozone and procaine induced differential morpho-functional modifications in platelets resulting in an increased release of factors. In detail, ozone induced an increase in surface protrusions and open canalicular system dilation suggestive of a marked α-granule release, while procaine caused a decrease in surface protrusions and open canalicular system dilation but a remarkable increase in microvesicle release suggestive of high secretory activity. Consistently, nine of the thirteen platelet-derived factors analysed in the PRP serum significantly increased after treatment with ozone and/or procaine. Therefore, ozone and procaine proved to have a remarkable stimulating potential without causing any damage to platelets, probably because they act through physiological, although different, secretory pathways.
Topics: Ozone; Procaine; Endothelial Cells; Cytokines; Platelet-Rich Plasma
PubMed: 37817677
DOI: 10.4081/ejh.2023.3839 -
International Journal of Molecular... Sep 2023As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer...
As vaccination efforts against SARS-CoV-2 progress in many countries, there is still an urgent need for efficient antiviral treatment strategies for those with severer disease courses, and lately, considerable efforts have been undertaken to repurpose existing drugs as antivirals. The local anaesthetic procaine has been investigated for antiviral properties against several viruses over the past decades. Here, we present data on the inhibitory effect of the procaine prodrugs ProcCluster and procaine hydrochloride on SARS-CoV-2 infection in vitro. Both procaine prodrugs limit SARS-CoV-2 progeny virus titres as well as reduce interferon and cytokine responses in a proportional manner to the virus load. The addition of procaine during the early stages of the SARS-CoV-2 replication cycle in a cell culture first limits the production of subgenomic RNA transcripts, and later affects the replication of the viral genomic RNA. Interestingly, procaine additionally exerts a prominent effect on SARS-CoV-2 progeny virus release when added late during the replication cycle, when viral RNA production and protein production are already largely completed.
Topics: Animals; Chlorocebus aethiops; SARS-CoV-2; COVID-19; Antiviral Agents; Anesthetics, Local; Prodrugs; Vero Cells; Procaine; Virus Replication
PubMed: 37834031
DOI: 10.3390/ijms241914584 -
Journal of Nuclear Medicine : Official... Sep 2023Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally...
Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells. Here, we report the use of human epidermal growth factor receptor 2 (HER2) Ac-pretargeted radioimmunotherapy (PRIT) to treat a mouse model of human EOC SKOV3 xenografts growing as peritoneal carcinomatosis (PC). On day 0, 10 SKOV3 cells transduced with a luciferase reporter gene were implanted intraperitoneally in nude mice, and tumor engraftment was verified by bioluminescent imaging (BLI). On day 15, treatment was started using 1 or 2 cycles of 3-step anti-HER2 Ac-PRIT (37 kBq/cycle as Ac- DOTA), separated by a 1-wk interval. Efficacy and toxicity were monitored for up to 154 d. Untreated PC-tumor-bearing nude mice showed a median survival of 112 d. We used 2 independent measures of response to evaluate the efficacy of Ac-PRIT. First, a greater proportion of the treated mice (9/10 1-cycle and 8/10 2-cycle; total, 17/20; 85%) survived long-term compared with controls (9/27, 33%), and significantly prolonged survival was documented (log-rank [Mantel-Cox] = 0.0042). Second, using BLI, a significant difference in the integrated BLI signal area to 98 d was noted between controls and treated groups ( = 0.0354). Of a total of 8 mice from the 2-cycle treatment group (74 kBq total) that were evaluated by necropsy, kidney radiotoxicity was mild and did not manifest itself clinically (normal serum blood urea nitrogen and creatinine). Dosimetry estimates (relative biological effectiveness-weighted dose, where relative biological effectiveness = 5) per 37 kBq administered for tumors and kidneys were 56.9 and 16.1 Gy, respectively. One-cycle and 2-cycle treatments were equally effective. With immunohistology, mild tubular changes attributable to α-toxicity were observed in both therapeutic groups. Treatment of EOC PC-tumor-bearing mice with anti-HER2 Ac-PRIT resulted in histologic cures and prolonged survival with minimal toxicity. Targeted α-therapy using the anti-HER2 Ac-PRIT system is a potential treatment for otherwise incurable EOC.
Topics: Humans; Animals; Mice; Radioimmunotherapy; Mice, Nude; Peritoneal Neoplasms; Radioisotopes; Cell Line, Tumor
PubMed: 37348919
DOI: 10.2967/jnumed.122.265095 -
Journal of Autoimmunity Feb 2024The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by... (Review)
Review
The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.
Topics: United States; Adult; Child; Humans; Male; Female; Penicillin G Procaine; Anaphylaxis; Penicillins; Hallucinations; Syndrome; Lung Diseases
PubMed: 38194789
DOI: 10.1016/j.jaut.2023.103164 -
Cureus Feb 2024First developed in the 1960s in Europe and approved briefly for use in the United States, fenethylline (sold as Captagon, one of its early trade names) is now a... (Review)
Review
First developed in the 1960s in Europe and approved briefly for use in the United States, fenethylline (sold as Captagon, one of its early trade names) is now a prominent drug of abuse in the Eastern Mediterranean Region. The drug was withdrawn from the United States market because of side effects that included hallucinations, visual distortions, and psychosis; it has also been linked to rare cases of myocardial infarction, seizures, and delusions. The chemical synthesis of fenethylline is straightforward and inexpensive. Manufactured in clandestine labs in Southern Europe and the Middle East, these amphetamines had been used by affluent Middle Eastern young people for recreation or study aids. Captagon has periodically emerged as a drug used in combat and conflict, and it was implicated in the 2015 riots in Paris. It has been described as "chemical courage" for combatants giving them focus, energy, and endurance in battle situations. Captagon is addictive but no cases of direct captagon-associated mortality have been reported. The use of drugs in war is nothing new, but captagon is also used heavily in the civilian population in war-torn areas to help them cope with food insecurity and maintain courage in dangerous situations. Captagon production and distribution drives the Syrian economy, but the drug's use is limited to certain regions and is rarely seen in North America. The drug is available online, but product may be contaminated with the inclusion of procaine, caffeine, or other substances.
PubMed: 38550445
DOI: 10.7759/cureus.55053 -
Journal of Clinical Medicine Nov 2023The use of low-dose local anesthetics (LAs) has significantly transformed patient care by providing rapid and effective relief of pain and other clinical conditions... (Review)
Review
The use of low-dose local anesthetics (LAs) has significantly transformed patient care by providing rapid and effective relief of pain and other clinical conditions while minimizing recovery time. This study aims to identify and describe the existing scientific evidence on the therapeutic use of low-dose LAs in various conditions and to identify gaps in the current literature in order to prioritize future research. This systematic scoping review adhered to the methodological guidelines outlined in the Arksey and O'Malley framework, which includes five distinct stages. Of the 129 studies included, 37.98% ( = 49) were clinical trials, 55.03% ( = 71) were observational studies, and 6.97% ( = 9) were systematic reviews. The most commonly reported indication for the use of low-dose LAs was chronic pain management (72.86%), followed by acute pain management (13.17%). Additionally, non-pain-related indications were also identified (13.95%). Overall, the administration of low-dose, short-acting LAs demonstrated favorable outcomes in terms of pain management and reduction in anxiety and depression scales, thereby having a positive impact on the patients' quality of life. This review represents the first systematic scoping review regarding the therapeutic role of LAs. To substantiate the reported positive effects on efficacy and safety, further rigorous research comprising larger, well-designed randomized controlled trials (RCTs) and long-term outcome monitoring is imperative.
PubMed: 38068272
DOI: 10.3390/jcm12237221