ABSTRACT
Neonatal platelets present a reduced response to the platelet agonist, thrombin (Thr), thus resulting in a deficient Thr-induced aggregation. These alterations are more pronounced in premature newborns. Here, our aim was to uncover the causes underneath the impaired Ca2+ homeostasis described in neonatal platelets. Both Ca2+ mobilization and Ca2+ influx in response to Thr are decreased in neonatal platelets compared to maternal and control woman platelets. In neonatal platelets, we observed impaired Ca2+ mobilization in response to the PAR-1 agonist (SFLLRN) or by blocking SERCA3 function with tert-butylhydroquinone. Regarding SOCE, the STIM1 regulatory protein, SARAF, was found overexpressed in neonatal platelets, promoting an increase in STIM1/SARAF interaction even under resting conditions. Additionally, higher interaction between SARAF and PDCD61/ALG2 was also observed, reducing SARAF ubiquitination and prolonging its half-life. These results were reproduced by overexpressing SARAF in MEG01 and DAMI cells. Finally, we also observed that pannexin 1 permeability is enhanced in response to Thr in control woman and maternal platelets, but not in neonatal platelets, hence, leading to the deregulation of the Ca2+ entry found in neonatal platelets. Summarizing, we show that in neonatal platelets both Ca2+ accumulation in the intracellular stores and Thr-evoked Ca2+ entry through either capacitative channels or non-selective channels are altered in neonatal platelets, contributing to deregulated Ca2+ homeostasis in neonatal platelets and leading to the altered aggregation observed in these subjects.
Subject(s)
Membrane Proteins , Thrombin , Infant, Newborn , Humans , Thrombin/metabolism , Membrane Proteins/metabolism , Blood Platelets/metabolism , Homeostasis , Calcium/metabolism , Calcium SignalingABSTRACT
BACKGROUND: Altered intracellular Ca2+ homeostasis in neonatal platelets has been previously reported. This study aims to examine the changes in the Ca2+ entry through the store-operated calcium entry (SOCE) mechanism in neonatal platelets. METHODS: Human platelets from either control women, mothers, and neonates were isolated and, following, were fixed after being treated as required. Platelet samples were analyzed by Western blotting, qRT-PCR, and MALDITOF/TOF. Ca2+ homeostasis was also determined. Culture cells were used as surrogated of platelets to overexpress the proteins of interest to reproduce the alterations observed in platelets. RESULTS: Altered TG (thapsigargin)-evoked SOCE, alternative molecular weight form of STIM1 (stromal interaction molecule 1; s-STIM1 [short STIM1 isoform (478 aa)], around 60 kDa) and overexpression of SARAF (SOCE-associated regulatory factor) were found in neonatal platelets as compared to maternal and control women platelets. s-STIM1 may result due to CAPN1 (calpain1)-dependent processing, as confirmed in platelets and MEG01 cells by using calpeptin and overexpressing CAPN1, respectively. In HEK293 (STIM1 and STIM2 [stromal interaction molecule 2] double knockout) cells transfected either with c-STIM1 (canonical STIM1 [685 aa]), s-STIM1 (478), STIM1B (540), and CAPN1 overexpression plasmids, we found s-STIM1 and c-STIM1, except in cells overexpressing s-STIM1 (478) that lacked CAPN1 target residues. These results and the in silico analysis, lead us to conclude that STIM1 is cleaved at Q496 by CAPN1. Ca2+ imaging analysis and coimmunoprecipitation assay using MEG01 and HEK293 cells overexpressing SARAF together with s-STIM1 (478) reported a reduced slow Ca2+-dependent inactivation, so reproducing the Ca2+-homeostasis pattern observed in neonatal platelets. CONCLUSIONS: CAPN1 may cleave STIM1 in neonatal platelets, hence, impairing SARAF coupling after SOCE activation. s-STIM1 may avoid slow Ca2+-dependent inactivation and, subsequently, results in an enhanced TG-evoked SOCE as observed in neonatal platelets.
Subject(s)
Blood Platelets , Calpain , Membrane Proteins , Stromal Interaction Molecule 1 , Female , Humans , Infant, Newborn , Blood Platelets/metabolism , Calcium/metabolism , Calcium Signaling , Calpain/metabolism , HEK293 Cells , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , ORAI1 Protein/genetics , ORAI1 Protein/metabolism , Stromal Interaction Molecule 1/genetics , Stromal Interaction Molecule 1/metabolismABSTRACT
The cornea transplant is considered the most frequently performed type of transplant in the world, with a demand that has been increasing in recent years. An observational descriptive study was conducted, focusing on the ocular tissue extracted from cadaveric donors from January 2019 to December 2021 at the Red Cross Eye Bank in Medellin, Colombia. This is the first epidemiological characterization of corneal donor tissues within the eye banks of our city, where high rates of violence-related deaths explain that tissue donors are mostly young individuals. This, in turn, results in excellent counts of endothelial cells and tissue viability in their microscopic studies. Additionally, there are lower rates of discarded tissues compared to similar studies.
Subject(s)
Cornea , Corneal Transplantation , Eye Banks , Tissue Donors , Colombia , Humans , Adult , Female , Middle Aged , Male , Eye Banks/statistics & numerical data , Aged , Young Adult , Adolescent , Aged, 80 and over , CitiesABSTRACT
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.
Subject(s)
Epistasis, Genetic , Genetic Predisposition to Disease , Polycystic Ovary Syndrome , Polymorphism, Single Nucleotide , Humans , Polycystic Ovary Syndrome/genetics , Female , Adult , Colombia/epidemiology , Genome-Wide Association Study , Case-Control Studies , Genotype , Young AdultABSTRACT
This study evaluated the effect of cobiotic (CO) composed of organic fructans powder of Agave tequilana and turmeric powder of Curcuma longa L. as an alternative of antibiotic growth promoters (AGPs) on growth performance, blood parameters, intestinal pH, oxidative stress, and cytokines serum levels of broiler chickens. A total of 135 one-day-old Ross 308 broilers distributed to five experimental groups, which included starter or finisher standard diets without AGPs (CON), CON + 0.25 COLI-ZIN g/kg feed (AGP), CON + 0.1 g Agave fructans/kg feed (AF), CON + 0.5 g turmeric powder/kg feed (TP) and CON + 0.1 g AF + 0.5 g TP /kg feed (CO), for 49 days. AF followed by TP, decreased feed intake, obtaining the best FCR. AGP increased the heterophil-lymphocyte ratio compared to other groups. CO significantly decreased the pH of the cecal content. AF increased IL-10 levels, while TP decreased it. AF decreased the IL-1ß levels. The present study showed that including a cobiotic based on AF and TP or components separately in a broilers diet improved growth performance, modified intestinal and cecum pH, and stimulated the immune system, which suggests CO as a safe alternative to AGP.
Subject(s)
Agave , Animal Feed , Chickens , Diet , Dietary Supplements , Fructans , Oxidative Stress , Animals , Chickens/growth & development , Chickens/immunology , Chickens/blood , Fructans/administration & dosage , Fructans/pharmacology , Animal Feed/analysis , Dietary Supplements/analysis , Oxidative Stress/drug effects , Agave/chemistry , Diet/veterinary , Cytokines/blood , Cytokines/metabolism , Male , Curcuma/chemistry , Animal Nutritional Physiological Phenomena/drug effectsABSTRACT
PURPOSE: Articular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep. METHODS: A full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer's lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems. RESULTS: The PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months. CONCLUSIONS: The results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.
Subject(s)
Cartilage Diseases , Cartilage, Articular , Platelet-Rich Plasma , Animals , Sheep , Knee Joint/surgery , Cartilage, Articular/pathology , Cartilage Diseases/pathology , Chondrocytes/transplantationABSTRACT
Hypoxia is considered to be a stressful physiological condition, which may occur during labor and the later stages of pregnancy as a result of, among other reasons, an aged placenta. Therefore, when gestation or labor is prolonged, low oxygen supply to the tissues may last for minutes, and newborns may present breathing problems and may require resuscitation maneuvers. As a result, poor oxygen supply to tissues and to circulating cells may last for longer periods of time, leading to life-threatening conditions. In contrast to the well-known platelet activation that occurs after reperfusion of the tissues due to an ischemia/reperfusion episode, platelet alterations in response to reduced oxygen exposition following labor have been less frequently investigated. Newborns overcome temporal hypoxic conditions by changing their organ functions or by adaptation of the intracellular molecular pathways. In the present review, we aim to analyze the main platelet modifications that appear at the protein level during hypoxia in order to highlight new platelet markers linked to complications arising from temporal hypoxic conditions during labor. Thus, we demonstrate that hypoxia modifies the expression and activity of hypoxic-response proteins (HRPs), including hypoxia-induced factor (HIF-1), endoplasmic reticulum oxidase 1 (Ero1), and carbonic anhydrase (CIX). Finally, we provide updates on research related to the regulation of platelet function due to HRP activation, as well as the role of HRPs in intracellular Ca2+ homeostasis.
Subject(s)
Carbonic Anhydrases , Labor, Obstetric , Infant, Newborn , Pregnancy , Female , Humans , Aged , Hypoxia/metabolism , Oxygen/metabolism , Placenta/metabolism , Carbonic Anhydrases/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolismABSTRACT
This study performs an analysis that will enable the evaluation of the quality, durability, and structure of repaired cartilaginous extracellular matrix tissue using an autologous-based particulated autograft cartilage and platelet-rich plasma treatment (PACI + PRP). A single-blind controlled experiment was conducted on 28 sheep to evaluate the efficacy of the PACI + PRP treatment for cartilage defects. Full-thickness 8 mm diameter defects were created in the weight-bearing area of both knees. The right knees received PACI + PRP. The left knees were treated with Ringer's lactate solution (RLS) or hyaluronic acid (HA) injections. Sheep were euthanized at 9- or 18-months post-surgery. An extensive immunohistochemical analysis was performed to assess collagen types (I, II, III, V, VI, IX, X, XI) and aggrecan positivity. A semiquantitative scoring system provided a detailed evaluation of immunostaining. Collagens and aggrecan scores in the PACI + PRP groups were similar to healthy cartilage. Significant differences were found in collagens associated with matrix maturity (II and V), degradation (IX), structure and mechanics (VI), and hypertrophy (X) between healthy cartilage and RLS- or HA-repaired cartilage. The PACI + PRP treatment advanced the repair cartilage process in chondral defects with mature hyaline cartilage and enhanced the structural and mechanical qualities with better consistent cartilage, less susceptible to degradation and without hypertrophic formation over time.
Subject(s)
Cartilage Diseases , Cartilage, Articular , Platelet-Rich Plasma , Animals , Sheep , Cartilage, Articular/surgery , Aggrecans/genetics , Aggrecans/metabolism , Single-Blind Method , Cartilage Diseases/metabolism , Platelet-Rich Plasma/metabolism , Hyaluronic Acid/metabolism , Collagen/metabolismABSTRACT
BACKGROUND: Lateral epicondylitis is common in workers who perform repetitive movements of the entire upper limb. Approximately 85%-90% of patients respond satisfactorily to conservative treatment, but in resistant patients, surgical treatment is considered. Classic open surgery is successful in between 70% and 97% of patients, similarly to more modern techniques such as arthroscopy. We sought to demonstrate the superiority of the Wolff technique in terms of clinical results. The goals of this study were to compare the functional and pain outcomes of arthroscopic surgery with open surgery using fasciotomy via the Wolff technique in the treatment of lateral epicondylitis. METHODS: This was a retrospective study of 47 working-age patients with resistant lateral epicondylitis: 27 underwent arthroscopic surgery and 20 underwent open surgery. Visual analog scale scores for pain and function, as well as the QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score, Mayo Elbow Performance Score, and Broberg and Morrey Rating System score, were collected preoperatively and postoperatively; return to patients' previous work and surgical time were also recorded. RESULTS: No statistically significant differences were observed between the groups in the reduction in the visual analog scale score (5.26 in arthroscopy group vs. 5.75 in fasciotomy group, P = .5), QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score (19 vs. 19.4, P = .9), Mayo Elbow Performance Score (82 vs. 81.5, P = .8), or Broberg and Morrey Rating System score (81.9 vs. 82.6, P = .9). The differences in terms of time off were also not statistically significant. The period of work leave corresponded, on average, to 83.78 days in the arthroscopy group and 89.95 days in the Wolff group. The mean surgical time was 44.2 minutes in the group undergoing arthroscopic intervention and 27.5 minutes in the fasciotomy group, showing a statistically significant difference (P < .001). CONCLUSIONS: Arthroscopic surgery and open surgery provide similar functional results and pain reduction in the treatment of lateral epicondylitis.
Subject(s)
Tennis Elbow , Arthroscopy/methods , Elbow , Follow-Up Studies , Humans , Pain/etiology , Retrospective Studies , Tennis Elbow/surgery , Treatment OutcomeABSTRACT
Spores of firmicute species contain 100s of mRNAs, whose major function in Bacillus subtilis is to provide ribonucleotides for new RNA synthesis when spores germinate. To determine if this is a general phenomenon, RNA was isolated from spores of multiple firmicute species and relative mRNA levels determined by transcriptome sequencing (RNA-seq). Determination of RNA levels in single spores allowed calculation of RNA nucleotides/spore, and assuming mRNA is 3% of spore RNA indicated that only â¼6% of spore mRNAs were present at >1/spore. Bacillus subtilis, Bacillus atrophaeus, and Clostridioides difficile spores had 49, 42, and 51 mRNAs at >1/spore, and numbers of mRNAs at ≥1/spore were â¼10 to 50% higher in Geobacillus stearothermophilus and Bacillus thuringiensis Al Hakam spores and â¼4-fold higher in Bacillus megaterium spores. In all species, some to many abundant spore mRNAs (i) were transcribed by RNA polymerase with forespore-specific σ factors, (ii) encoded proteins that were homologs of those encoded by abundant B. subtilis spore mRNAs and are proteins in dormant spores, and (iii) were likely transcribed in the mother cell compartment of the sporulating cell. Analysis of the coverage of RNA-seq reads on mRNAs from all species suggested that abundant spore mRNAs were fragmented, as was confirmed by reverse transcriptase quantitative PCR (RT-qPCR) analysis of abundant B. subtilis and C. difficile spore mRNAs. These data add to evidence indicating that the function of at least the great majority of mRNAs in all firmicute spores is to be degraded to generate ribonucleotides for new RNA synthesis when spores germinate. IMPORTANCE Only â¼6% of mRNAs in spores of six firmicute species are at ≥1 molecule/spore, many abundant spore mRNAs encode proteins similar to B. subtilis spore proteins, and some abundant B. subtilis and C. difficile spore mRNAs were fragmented. Most of the abundant B. subtilis and other Bacillales spore mRNAs are transcribed under the control of the forespore-specific RNA polymerase σ factors, F or G, and these results may stimulate transcription analyses in developing spores of species other than B. subtilis. These findings, plus the absence of key nucleotide biosynthetic enzymes in spores, suggest that firmicute spores' abundant mRNAs are not translated when spores germinate but instead are degraded to generate ribonucleotides for new RNA synthesis by the germinated spore.
Subject(s)
Firmicutes/genetics , RNA, Bacterial/metabolism , RNA, Messenger/metabolism , Spores, Bacterial/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/metabolism , Firmicutes/enzymology , Firmicutes/metabolism , RNA, Bacterial/genetics , RNA, Messenger/genetics , Spores, Bacterial/metabolismABSTRACT
Bacteria have a repertoire of strategies to overcome antibiotics in clinical use, complicating our ability to treat and cure infectious diseases. In addition to evolving resistance, bacteria within genetically clonal cultures can undergo transient phenotypic changes and tolerate high doses of antibiotics. These cells, termed persisters, exhibit heterogeneous phenotypes; the strategies that a bacterial population deploys to overcome one class of antibiotics can be distinct from those needed to survive treatment with drugs with another mode of action. It was previously reported that fluoroquinolones, which target DNA topoisomerases, retain the capacity to kill nongrowing bacteria that tolerate other classes of antibiotics. Here, we show that in Escherichia coli stationary-phase cultures and colony biofilms, persisters that survive treatment with the anionic fluoroquinolone delafloxacin depend on the AcrAB-TolC efflux pump. In contrast, we did not detect this dependence on AcrAB-TolC in E. coli persisters that survive treatment with three other fluoroquinolone compounds. We found that the loss of AcrAB-TolC activity via genetic mutations or chemical inhibition not only reduces delafloxacin persistence in nongrowing E. coli MG1655 or EDL933 (an E. coli O157:H7 strain), but it limits resistance development in progenies derived from delafloxacin persisters that were given the opportunity to recover in nutritive medium following antibiotic treatment. Our findings highlight the heterogeneity in defense mechanisms that persisters use to overcome different compounds within the same class of antibiotics. They further indicate that efflux pump inhibitors can potentiate the activity of delafloxacin against stationary-phase E. coli and block resistance development in delafloxacin persister progenies.
Subject(s)
Escherichia coli Proteins , Escherichia coli , Anti-Bacterial Agents/pharmacology , Carrier Proteins , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Fluoroquinolones/pharmacologyABSTRACT
Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less abundant collagens are type III, IV, V, VI, X, XII, XIV, XVI, XXII, and XXVII collagens. All these collagens have been found to play a key role in healthy cartilage, regardless of whether they are more or less abundant. Additionally, an exhaustive evaluation of collagen fibrils in a repaired cartilage tissue after a chondral lesion is necessary to determine the quality of the repaired tissue and even whether or not this repaired tissue is considered hyaline cartilage. Therefore, this review aims to describe in depth all the collagen types found in the normal articular cartilage structure, and based on this, establish the parameters that allow one to consider a repaired cartilage tissue as a hyaline cartilage.
Subject(s)
Cartilage Diseases/metabolism , Cartilage, Articular/metabolism , Collagen/metabolism , Hyaline Cartilage/metabolism , Animals , Cartilage Diseases/pathology , Cartilage, Articular/pathology , Humans , Hyaline Cartilage/pathologyABSTRACT
OBJECTIVE: To assess the effect of continuous wound infusion (CWI) with preperitoneal ropivacaine on postoperative analgesia and compare it with the epidural administration of ropivacaine and morphine in bitches undergoing ovariohysterectomy. STUDY DESIGN: A parallel, randomized, clinical, prospective and nonblinded study. ANIMALS: A group of 38 Greyhound bitches. METHODS: In the catheter group (CathG), CWI with ropivacaine 1% (1 mg kg-1 + 0.8 mg kg-1 hour-1) was applied to the preperitoneal space over the surgical incision. In the epidural group (EpiG), ropivacaine 0.5% (1.3 mg kg-1) and morphine (0.1 mg kg-1) were epidurally administered. Occipital-coccygeal length was used to calculate the volume for the epidural. Pain was scored using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale-short form (CMPS-SF) before anaesthesia and at 2, 4, 6, 18, 21 and 24 hours after extubation. Incisional sensitivity using a dynamometer (MWTs-incision) was evaluated simultaneously. Plasma ropivacaine and cortisol concentrations, degree of sedation, motor blockade and response to interdigital clamping were measured or assessed. A two-way mixed analysis of variance and a Mann-Whitney U test were used to analyse data; p < 0.05. RESULTS: No differences were detected in the DIVAS (p = 0.301), CMPS-SF (p = 0.600) scores, MWTs-incision measurements (p = 0.257) and cortisol values (p = 0.878) between the groups. Rescue analgesia was required in two dogs, one in each group, at 2 hours. Sedation, motor blockade and negative response to interdigital clamping were detected in EpiG at 2, 4 and 6 hours. Mean plasma ropivacaine values were higher in CathG (0.475 ± 0.164 ng mL-1) than in EpiG (0.184 ± 0.213 ng mL-1; p = 0.001). CONCLUSION AND CLINICAL RELEVANCE: Compared with epidural ropivacaine and morphine, CWI with preperitoneal ropivacaine is an effective analgesic technique for postoperative pain management in bitches undergoing ovariohysterectomy without motor blockade.
Subject(s)
Analgesia, Epidural , Analgesia , Dog Diseases , Amides , Analgesia/veterinary , Analgesia, Epidural/veterinary , Analgesics, Opioid , Anesthetics, Local , Animals , Dogs , Morphine , Pain, Postoperative/prevention & control , Pain, Postoperative/veterinary , Prospective Studies , RopivacaineABSTRACT
This study examined the microbicidal activity of 222-nm UV radiation (UV222), which is potentially a safer alternative to the 254-nm UV radiation (UV254) that is often used for surface decontamination. Spores and/or growing and stationary-phase cells of Bacillus cereus, Bacillus subtilis, Bacillus thuringiensis, Staphylococcus aureus, and Clostridioides difficile and a herpesvirus were all killed or inactivated by UV222 and at lower fluences than with UV254B. subtilis spores and cells lacking the major DNA repair protein RecA were more sensitive to UV222, as were spores lacking their DNA-protective proteins, the α/ß-type small, acid-soluble spore proteins. The spore cores' large amount of Ca2+-dipicolinic acid (â¼25% of the core dry weight) also protected B. subtilis and C. difficile spores against UV222, while spores' proteinaceous coat may have given some slight protection against UV222 Survivors among B. subtilis spores treated with UV222 acquired a large number of mutations, and this radiation generated known mutagenic photoproducts in spore and cell DNA, primarily cyclobutane-type pyrimidine dimers in growing cells and an α-thyminyl-thymine adduct termed the spore photoproduct (SP) in spores. Notably, the loss of a key SP repair protein markedly decreased spore UV222 resistance. UV222-treated B. subtilis spores germinated relatively normally, and the generation of colonies from these germinated spores was not salt sensitive. The latter two findings suggest that UV222 does not kill spores by general protein damage, and thus, the new results are consistent with the notion that DNA damage is responsible for the killing of spores and cells by UV222IMPORTANCE Spores of a variety of bacteria are resistant to common decontamination agents, and many of them are major causes of food spoilage and some serious human diseases, including anthrax caused by spores of Bacillus anthracis Consequently, there is an ongoing need for efficient methods for spore eradication, in particular methods that have minimal deleterious effects on people or the environment. UV radiation at 254 nm (UV254) is sporicidal and commonly used for surface decontamination but can cause deleterious effects in humans. Recent work, however, suggests that 222-nm UV (UV222) may be less harmful to people than UV254 yet may still kill bacteria and at lower fluences than UV254 The present work has identified the damage by UV222 that leads to the killing of growing cells and spores of some bacteria, many of which are human pathogens, and UV222 also inactivates a herpesvirus.
Subject(s)
Bacillus/radiation effects , Clostridioides difficile/radiation effects , DNA Damage , Simplexvirus/radiation effects , Spores, Bacterial/radiation effects , Staphylococcus aureus/radiation effects , Bacillus/physiology , Clostridioides difficile/physiology , Simplexvirus/physiology , Spores, Bacterial/physiology , Staphylococcus aureus/physiology , Ultraviolet Rays/adverse effectsABSTRACT
BACKGROUND: Pertussis is a highly contagious disease of public health interest caused by the bacterium Bordetella pertussis. Although its incidence has decreased substantially after the introduction of a vaccination, the burden of the disease remains high. Although the paroxysmal phase is highly disabling, complications are uncommon and more prevalent in children than in adults. The most frequent neurological complication is encephalopathy, but seizures, paresis, paraplegia, ataxias, aphasias, and decerebration postures have also been described. The complication of decerebration postures has not been previously reported in adults. CASE PRESENTATION: We present a video case of an adult HIV patient with severe coughing paroxysms, post-tussive emesis and syncope, whose workup confirmed the diagnosis of a B. pertussis respiratory infection. During hospitalization, he had fluctuant encephalopathy and post-tussive decerebration postures following paroxysms. He was treated with antibiotic therapy and finally sent home without residual neurological deficits. CONCLUSION: This case illustrates the biological plausibility of neurologic complications of pertussis in adults, which, albeit rare, can cause important morbidities. Future research should explore whether there are differences in the clinical presentation, risk factors and pathophysiology of the disease among adults or interventions aimed at preventing or treating pertussis encephalopathy.
Subject(s)
AIDS-Related Opportunistic Infections/complications , Bordetella pertussis/genetics , Brain Diseases/complications , Decerebrate State/complications , HIV , Whooping Cough/complications , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/virology , Anti-Bacterial Agents/therapeutic use , Bordetella pertussis/isolation & purification , Brain Diseases/drug therapy , Brain Diseases/microbiology , Decerebrate State/drug therapy , Decerebrate State/microbiology , Hospitalization , Humans , Male , Middle Aged , Polymerase Chain Reaction , Risk Factors , Treatment Outcome , Whooping Cough/drug therapy , Whooping Cough/microbiologyABSTRACT
BACKGROUND: Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemia-reperfusion. Immunohistochemical analysis was performed using caspase-3. RESULTS: During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups. CONCLUSIONS: MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemia-reperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.
Subject(s)
Enzyme Inhibitors/pharmacology , Intestinal Diseases/veterinary , Methylene Blue/pharmacology , Reperfusion Injury , Animals , Hemodynamics/drug effects , RabbitsABSTRACT
Social media platforms are low-cost tools that can be used to address issues in public health nutrition, especially in countries where health-related institutions experience economic limitations. We aimed to emphasize the benefits of using social media to promote health that have been documented to date. To show social media's positive impact on population health literacy, we briefly describe an inexpensive systematic communication strategy implemented in our research center through 2 social media platforms, the lessons learned, and the strategy's short-term results. Because social media use in public health is a new field of study, this perspective also focuses on the current limitations and gaps in evidence that need to be addressed to translate the best practices into policy recommendations. In conclusion, the perspective highlights the role that health actors and governments should take to maximize the benefits of social media use.
Subject(s)
Health Promotion/methods , Public Health/instrumentation , Social Media , Health Literacy , Humans , Information Dissemination/methods , Latin AmericaABSTRACT
OBJECTIVE: To review monitors currently available for the assessment of nociception-antinociception in veterinary medicine. DATABASES USED: PubMed, Web of Science and Google Scholar. The results were initially filtered manually based on the title and the abstract. CONCLUSIONS: The provision of adequate antinociception is difficult to achieve in veterinary anaesthesia. Currently, heart rate and arterial blood pressure are used to monitor the response to a noxious stimulus during anaesthesia, with minimum alveolar concentration-sparing effect and stress-related hormones used for this purpose in research studies. However, since none of these variables truly assess intraoperative nociception, several alternative monitoring devices have been developed for use in humans. These nociceptive-antinociceptive monitoring systems derive information from variables, such as electroencephalography, parasympathetic nervous system (PNS) response, sympathetic nervous system response and electromyography. Several of these monitoring systems have been investigated in veterinary medicine, although few have been used to assess intraoperative nociception in animals. There is controversy regarding their effectiveness and clinical use in animals. A nociceptive-antinociceptive monitoring system based on the PNS response has been developed for use in cats, dogs and horses. It uses the parasympathetic tone activity index, which is believed to detect inadequate intraoperative nociception-antinociception balance in veterinary anaesthesia. Nonetheless, there are limited published studies to date, and cardiovascular variables remain the gold standard. Consequently, further studies in this area are warranted.
Subject(s)
Analgesics/pharmacology , Anesthesia/veterinary , Intraoperative Complications/veterinary , Monitoring, Physiologic , Pain Measurement/veterinary , Analgesics/administration & dosage , Animals , Pain Measurement/methodsABSTRACT
OBJECTIVE: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups). METHODS: Acetaminophen (10 and 20 mg kg-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg-1 hour-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg-1 hour-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg-1. CONCLUSIONS AND CLINICAL RELEVANCE: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.