Efficacy and Safety of Glycopyrrolate in the Management of Organophosphate and Carbamate Poisoning: A Systematic Review.

OBJECTIVE: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning. METHODOLOGY: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer. RESULTS: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group. CONCLUSION: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

Caveolin-1 peptide regulates p53-microRNA-34a feedback in fibrotic lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease resulting from dysregulated repair responses to lung injury. Excessive extracellular matrix deposition by expanding myofibroblasts and fibrotic lung fibroblasts (fLfs) has been implicated in the pathogenesis of PF, including IPF. We explored fLfs' microRNA-34a (miR-34a) expression from IPF tissues. Basal miR-34a levels were decreased with reduced binding of p53 to the promoter DNA and 3'UTR mRNA sequences. Overexpression of miR-34a in fLfs increased p53, PAI-1, and reduced pro-fibrogenic markers. The regulatory effects of miR-34a were altered by modifying the p53 expression. Precursor-miR-34a lung transduction reduced bleomycin-induced PF in wild-type mice. fLfs treated with caveolin-1 scaffolding domain peptide (CSP) or its fragment, CSP7, restored miR-34a, p53, and PAI-1. CSP/CSP7 reduced PDGFR-ß and pro-fibrogenic markers, which was abolished in fLfs following blockade of miR-34a expression. These peptides failed to resolve PF in mice lacking miR-34a in fLfs, indicating miR-34a-p53-feedback induction required for anti-fibrotic effects.

Adverse drug reactions of GLP-1 agonists: A systematic review of case reports.

BACKGROUND AND AIM: The importance of glucagon-like peptide-1 (GLP-1) agonists is increasing because of its blood sugar controlling and weight loss properties. The data regarding safety of GLP-1 agonists are limited. This study aims to review case reports and case series on adverse drug reactions (ADRs) of GLP-1 agonist. METHODOLOGY: A comprehensive search was performed in PubMed/Medline, Scopus and Embase to identify literatures. Bibliographic search and open search in Google, Google Scholar, SpringerLink and ResearchGate was performed to identify additional studies. Case reports and case series published the ADRs by the use of GLP-1 agonists in type 2 diabetes patients were included in the study. Reviews, experimental studies, observational studies, grey literature and non English studies were excluded. RESULTS: The study identified 120 cases of GLP-1 agonists associated ADRs (liraglutide - 46, exenatide - 46, dulaglutide - 20, semaglutide - 4, albiglutide - 2, lixisenatide - 2). The major ADRs reported was gastrointestinal disorders (n = 40) followed by renal (n = 23), dermatologic (n = 14), hepatic (n = 10), immunologic (n = 13), endocrine/metabolic (n = 7), hematologic (n = 3), angioedema (n = 3), neurologic (n = 2), cardiovascular (n = 2) and 1 from each of psychiatric, reproductive, generalized edema problems. CONCLUSION: Gastrointestinal problems, particularly pancreatitis was the more frequently reported adverse drug reaction associated with GLP-1 agonist. The most adverse drug reactions were observed with liraglutide and exenatide.

Lead exposure induces metabolic reprogramming in rat models.

Lead is a toxin of great public health concern affecting the young and aging population. Several factors such as age, gender, lifestyle, dose, and genetic makeup result in interindividual variations to lead toxicity mainly due to variations in metabolic consequences. Hence, the present study aimed to examine dose-dependent lead-induced systemic changes in metabolism using rat model by administering specific doses of lead such as 10 (low lead; L-Pb), 50 (moderate lead; M-Pb), and 100 mg/kg (high lead; H-Pb) body weight for a period of one month. Biochemical and haematological analysis revealed that H-Pb was associated with low body weight and feed efficiency, low total protein levels (p ≤ 0.05), high blood lead (Pb-B) levels (p ≤ 0.001), low ALAD (δ-aminolevulinate dehydratase) activity (p ≤ 0.0001), high creatinine (p ≤ 0.0001) and blood urea nitrogen (BUN) (p ≤ 0.01) levels, elevated RBC and WBC counts, reduced haemoglobin and blood cell indices compared to control. Spatial learning and memory test revealed that H-Pb exposed animals presented high latency to the target quadrant and escape platform compared to other groups indicating H-Pb alters cognition function in rats. Histopathological changes were observed in liver and kidney as they are the main target organs of lead toxicity. LC-MS analysis further revealed that Butyryl-L-carnitine (p ≤ 0.01) and Ganglioside GD2 (d18:0/20:0) (p ≤ 0.05) levels were significantly reduced in H-Pb group compared to all groups. Further, pathway enrichment analysis revealed abundance and significantly modulated metabolites associated with oxidative stress pathways. The present study is the first in vivo model of dose-dependent lead exposure for serum metabolite profiling.

Caveolin-1 scaffolding domain peptide regulates glucose metabolism in lung fibrosis.

Increased metabolism distinguishes myofibroblasts or fibrotic lung fibroblasts (fLfs) from the normal lung fibroblasts (nLfs). The mechanism of metabolic activation in fLfs has not been fully elucidated. Furthermore, the antifibrogenic effects of caveolin-1 scaffolding domain peptide CSP/CSP7 involving metabolic reprogramming in fLfs are unclear. We therefore analyzed lactate and succinate levels, as well as the expression of glycolytic enzymes and hypoxia inducible factor-1α (HIF-1α). Lactate and succinate levels, as well as the basal expression of glycolytic enzymes and HIF-1α, were increased in fLfs. These changes were reversed following restoration of p53 or its transcriptional target microRNA-34a (miR-34a) expression in fLfs. Conversely, inhibition of basal p53 or miR-34a increased glucose metabolism, glycolytic enzymes, and HIF-1α in nLfs. Treatment of fLfs or mice having bleomycin- or Ad-TGF-ß1-induced lung fibrosis with CSP/CSP7 reduced the expression of glycolytic enzymes and HIF-1α. Furthermore, inhibition of p53 or miR-34a abrogated CSP/CSP7-mediated restoration of glycolytic flux in fLfs in vitro and in mice with pulmonary fibrosis and lacking p53 or miR-34a expression in fibroblasts in vivo. Our data indicate that dysregulation of glucose metabolism in fLfs is causally linked to loss of basal expression of p53 and miR-34a. Treatment with CSP/CSP7 constrains aberrant glucose metabolism through restoration of p53 and miR-34a.

Knowledge Assessment of E-Bug Assisted Antimicrobial Resistance Education Module in Class VII School Students of South Indian Coastal Town of Manipal.

Antimicrobial resistance (AMR) is a recognized public health threat today globally. Although many active and passive stewardship strategies are advocated to counter AMR clinically, educating school going children on AMR could be a cost-effective measure to minimize AMR development in the future. We implemented NICE's e-bug as a module to educate class VII school students on AMR determinants. A prospective quasi-experimental study on 327 students from nine different schools of class VII around Manipal town, Udupi district, Karnataka state, India were included in the study. Ten questions on AMR determinants from the e-bug program were used in written pre-test. After an education intervention, a post-test was conducted. Descriptive statistics to estimate epidemiological characteristics, Wilcoxon Signed Ranks and Kruskal⁻Wallis tests were applied to analyze statistical significance of pre/post-test performance scores and between schools. Students had inadequate knowledge on seven AMR determinants (antimicrobial indication, its course, hand hygiene, fermentation, spread of infection, microbial multiplication and characteristics of microbe) as analyzed from the post-test performance (p < 0.05). Comparison of post-test performance between schools showed significant improvement in scores (p < 0.05) for three questions (definition on antimicrobial, cover while cough/sneezing and microbial characteristics). Although students exhibited sub-optimal knowledge on some AMR determinants, they showed keenness to learn, which was evident by their post-test performance. Our findings and previous similar studies from Europe are suggestive of early pedagogic interventions on AMR through inclusion of such education modules in the regular school curriculum could be a potential tool for AMR prevention.

Dynamic Relaxers of the Face.

Dynamics of the facial aesthetics is changing rapidly as we treat more and more faces. Our understanding of the molecule at hand and its various applications only expands as our learnings progress. Perception and expectation of the end goal to beauty itself are evolving, and therefore newer ways of analyzing, understanding, and delivering of any aesthetic drug have to evolve continuously. Botulinum toxin is one of the wonders in the aesthetic world, which led the entire focus of the medical fraternity into nonsurgical facial aesthetics. Botulinum toxin was and is still the best tool for relaxing lateral canthal lines and glabellar frown lines. However, it has evolved further to now impart changes/enhancements in skin texture and luminosity, enhancement in facial shape, and reduction in glandular activity of sebaceous, sweat, and salivary glands, therefore leading to a lot more aesthetic application while it still remains as the line eraser.

Estudio de bioequivalencia de formulación de prueba / Bioequivalence Study of Test Formulation Fibroneurina and Reference Formulation Fingolimod 0.5 mg hard capsules under fasting conditions

Conclusion Bioequivalence Results: A total of 40 subjects were planned and enrolled in the study. Thirty-nine (39) subjects completed the clinical phase of the study and data of thirty-nine (39) subjects were considered for pharmacokinetic and statistical analysis. The 90 % CI's of Ln-transformed parameters for Fingolimod are summarized below: Safety results: Two (02) AEs were reported during the clinical phase of the study which were unexpected and not related to study drug, mild in severity and were considered for lost to follow up. No serious AEs (SAEs) were observed during the clinical phase. Conclusion: Based on the statistical analysis of Fingolimod on 39 subjects, it is concluded that the Test Product (T): Fibroneurina manufactured by Laboratorios Bagó, Argentina shows bioequivalence with the Reference Product Fingolimod 0.5 mg hard capsules Manufactured by Novartis Pharma GmbH, Germany. Date of the report: 04 February 2017

ESTUDIO DE BIOEQUIVALENCIA DE FORMULACIÓN DE PRUEBA Fibroneurina y la formulación de referencia de prueba Fingolimed 0.5 mg. Cépsulas duras en condición de ayuno / Bioequivalence Study of Test Formulation Fibroneurina and Reference Formulation Fingolimod 0.5 mg hard capsules under fasting conditions

Conclusion Bioequivalence Results: A total of 40 subjects were planned and enrolled in the study. Thirty-nine (39) subjects completed the clinical phase of the study and data of thirty-nine (39) subjects were considered for pharmacokinetic and statistical analysis. The 90 % CI's of Ln-transformed parameters for Fingolimod are summarized below: Safety results: Two (02) AEs were reported during the clinical phase of the study which were unexpected and not related to study drug, mild in severity and were considered for lost to follow up. No serious AEs (SAEs) were observed during the clinical phase. Conclusion: Based on the statistical analysis of Fingolimod on 39 subjects, it is concluded that the Test Product (T): Fibroneurina manufactured by Laboratorios Bagó, Argentina shows bioequivalence with the Reference Product Fingolimod 0.5 mg hard capsules Manufactured by Novartis Pharma GmbH, Germany. Date of the report: 04 February 2017

Comparative evaluation of effect of use of toothbrush with paste and munident on levels of Streptococcus mutans and gingival health in children: An in vivo study.

AIM: Dental caries is a multifactorial disease which has a deleterious effect on the oral cavity. Improper oral hygiene habits are a cause for the same. The aim of this study was to compare the antibacterial efficacy of Munident, an Ayurvedic (herbal) dentifrice with commercially available toothpaste. MATERIALS AND METHODS: A total of forty subjects between the age group 9 and 12 years, resident of Bala Yeshu Nilaya Bhavan, Mangalore, Karnataka, India, were chosen for our study. They were divided into two groups containing twenty subjects in each; Group 1 for standard toothpaste and Group 2 for Munident. The decayed, missing, and filled teeth scores were noted from each subject. Group 1 was instructed to brush the teeth using commercially available toothpaste and Group 2 was instructed to brush using commercially available Munident (herbal) dentifrice. Both the groups brushed the teeth using soft variety of tooth brush. The gingival bleeding index and salivary Streptococcus mutans count were noted pre- and post-brushimg for both groups. The results obtained were subjected to statistical analysis. RESULTS: Munident (herbal) dentifrice showed better efficacy in comparison to toothpaste in terms of gingival bleeding index and salivary S. mutans count. CONCLUSION: Munident (herbal) dentifrice has better gingival bleeding index compared to standard formulation of toothpaste. Hence, the practice of using herbal dentifrice should be encouraged.

Consensus Recommendations for Treatment Strategies in Indians Using Botulinum Toxin and Hyaluronic Acid Fillers.

BACKGROUND: Indians constitute one of the largest population groups in the world. Facial anthropometry, morphology, and age-related changes in Indians differ from those of other ethnic groups, necessitating a good understanding of their facial structure and the required aesthetic treatment strategies. However, published recommendations specific to Indians are few, particularly regarding combination treatment. METHODS: The Indian Facial Aesthetics Expert Group (19 dermatologists, plastic surgeons, and aesthetic physicians with a mean 15.5 years' aesthetic treatment experience) met to develop consensus recommendations for the cosmetic facial use of botulinum toxin and hyaluronic acid fillers, alone and in combination, in Indians. Treatment strategies and dosage recommendations (agreed by ≥ 75% of the group) were based on results of a premeeting survey, peer-reviewed literature, and the experts' clinical experience. RESULTS: The need for combination treatment increases with age. Tear trough deficiency is the most common midface indication in Indian women aged 20-40 years. In older women, malar volume loss and jowls are the most common aesthetic concerns. Excess medial soft tissue on a relatively smaller midface precedes age-related sagging. Hence, in older Indians, fillers should be used peripherally to achieve lift and conservatively in the medial zones to avoid adding bulk medially. The shorter, wider lower face requires 3-dimensional correction, including chin augmentation, to achieve increased facial height and the oval shape desired by most Indian women. CONCLUSIONS: These recommendations give physicians treating Indians worldwide a better understanding of their unique facial characteristics and provide treatment strategies to achieve optimal aesthetic outcomes.

Outer Circle Versus Inner Circle: Special Considerations While Rejuvenating an Indian Face Using Fillers.

INTRODUCTION: An oval face, pronounced cheek bones, a defined jaw line and a smooth Ogee curve are global aesthetic beauty goals. Though criteria are similar the Indian face poses some unique challenges because of the innate differences in skeletal shape, size, and soft tissue disposition. Width of the malar prominences and mandibular angles along with height are smaller compared to the other Asian and Caucasian populations along with a much heavier soft tissue disposition. This creates unique deficits and places unique demands on aesthetic intervention. OBJECTIVES: The evolution of practice patterns has lead to a variety of newer approaches; however, it is still common to target the nasolabial and mid-face volumizing as basic intervention for facial beautifying and rejuvenation. As aging progresses, Indian faces tend to get fuller and the tissue then descends downwards similar to other ethnic groups albeit more aggressive due to higher volumes of facial fat pad and smaller bone framework. Any excess correction in the inner circle zones will further add to the bulk along with cumulative remnants of previously administered fillers. METHODS: In a younger face when the goal is beautification the attempt is to address the specific structural deficit on the outer bony framework along with the chin. This enhances the appearance immediately as well as holds up the tissue descent as they age. When the goal is youthful transition of an aging face, then again the bony changes further enhance the deficit in framework and the loss of fat pads along the periphery that is lateral forehead, temples and lateral cheek. Fat pad correction will give the most natural and best results as against working on the anterior mid cheek, nasolabials and angle of the mouth in a soft tissue heavy center zone of the face. Botulinum toxin and hyaluronic acid (HA) fillers remain the most popular facial injectables used for facial rejuvenation and structural enhancement. RESULTS: Naturally enhanced faces, and gracefully addressed aging changes are important. Fillers administered on the outer zones of the face rather than the inner zone gives better aesthetic results.

Dental health status among sensory impaired and blind institutionalized children aged 6 to 20 years.

BACKGROUND: This study was planned to assess the dental caries status among disabled children as dental health is an integral part of general body health and this group is deprived of health care needs. MATERIALS & METHODS: A sample of 310 disabled children was gathered including 195- Hearing impaired, 115 - blind. Of which 226 were males and 84 were females. A study questionnaire was prepared to include demographic information and WHO oral health assessment form (1997) to record dental caries status.Data was analysed using student's test and ANOVA test was used at p≤0.05. RESULTS: The overall mean for DMFT scores for males and females was 2.11 (1.753) and 1.75 (1.275) respectively. Similarly overall mean for dft was 0.31 (0.254) for males and 0.27 (0.143) for females. Mean DMFT of blind students was more as compared to hearing impaired ones as 2.16 (2.005) and 1.80 (1.264) respectively. Age factor showed a significant increase in the mean DMFT scores with advancing age at p ≤ 0.001. CONCLUSION: Overall mean scores of caries was very high and it increased with increasing age. Blind children experienced more caries then hearing impaired children in permanent, whereas it was opposite in primary dentition. So there is urgent need of both comprehensive and incremental dental care for this subgroup of population. How to cite the article: Sanjay V, Shetty SM, Shetty RG, Managoli NA, Gugawad SC, Hitesh D. Dental health status among sensory impaired and blind institutionalized children aged 6 to 20 years. J Int Oral Health 2014;6(1):55-8.

Under eye infraorbital injection technique: the best value in facial rejuvenation.

The use of fillers in esthetic rejuvenation or reshaping has been well established and is one of toughest techniques for beginners due to segmental attachments and proximity to important anatomical structures in the infraorbital area making it difficult to achieve smooth esthetic results. To make filling easy, smooth, and repeatable, anatomical points were marked through specific surface measurements. Patients were injected with 0.5-1 mL of hyaluronic acid filler using the identified anatomical point. All patients treated have achieved restoration of the ogee curve with no bruising and minimal downtime with results lasting for 12-36 months. The results of the study suggest the use of single repeatable injection at the crucial point and if required at multiple identified anatomical points along the ligamental attachment to satisfy the esthetic outcome of the patient. Injection of filler at infraorbital points could instantly lift the face up, elevating the point of shadow and shifting the point of highest light reflection to the ideal malar point.

No carious cervical lesions: abfraction.

Abfraction or Theory of Abfraction is a theory explaining the non-carious cervical lesions (NCCL). It suggests that they are caused by flexural forces, usually from cyclic loading; the enamel, especially at the cementoenamel junction (CEJ), undergoes this pattern of destruction by separating the enamel rods. Clinical aspect importance of these ineart lesions are at most important to be detected for early intervention and treatment modalities as options during the progression of the disease. How to cite this article: Shetty SM, Shetty RG, Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions: Abfraction. J Int Oral Health 2013; 5(5):142-5.

Compare the effcacy of two commercially available mouthrinses in reducing viable bacterial count in dental aerosol produced during ultrasonic scaling when used as a preprocedural rinse.

AIM: To evaluate and compare the effcacy of preprocedural mouthrinses (chlorhexidine digluconate and tea tree oil) in reducing microbial content of aerosol product during ultrasonic scaling procedures by viable bacterial count. SETTINGS AND DESIGN: It was a randomized single blind, placebo-controlled parallel group study. MATERIALS AND METHODS: Sixty subjects were randomly assigned to rinse 10 ml of any one of the mouthrinses (chlorhexidine digluconate or tea tree oil or distilled water). Ultrasonic scaling was done for a period of 10 minutes in presence of trypticase soy agar plates placed at standardized distance. Plates were then sent for microbiological evaluation for the aerosol produced. RESULTS: This study showed that all the antiseptic mouthwashes signifcantly reduced the bacterial colony forming units (CFUs) in aerosol samples. Chlorhexidine rinses were found to be superior to tea tree when used preprocedurally in reducing aerolized bacteria. CONCLUSION: This study advocates preprocedural dural rinsing with an effective antimicrobial mouthrinse during any dental treatment which generates aerosols, reduces the risk of cross-contamination with infectious agents in the dental operatory. CLINICAL SIGNIFICANCE: The aerolization of oral microbes occurring during dental procedures can potentially result in cross-contamination in the dental operatory and transmission of infectious agents to both dental professionals and patient. It is reasonable to assume therefore, that any stratagem for reducing the viable bacterial content of these aerosols could lower the risk of cross-contamination.

Increased prevalence of subclinical atherosclerosis in rheumatoid arthritis patients of Indian descent.

BACKGROUND: Studies have shown that rheumatoid arthritis (RA) patients are two to five times more likely to develop premature cardiovascular disease, thus shortening their life expectancy by five to 10 years. This risk has risen to approximately 12.6% in the urban population and 7.4% in the rural population of India. The Framingham risk score (FRS) identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. An investigation of the patients' coronary arteries and coronary artery calcification (CAC) - a measure of atherosclerotic plaque - has been found to be a strong predictor of cardiovascular disease. OBJECTIVE: To identify important biological markers for easy and non-invasive identification of cardiovascular disease in RA patients, and to investigate whether there is a relationship between the FRS and coronary artery atherosclerosis in RA patients. METHODS: The present study included 43 established RA patients and 50 healthy individuals (controls). Traditional and nontraditional risk factors were studied and compared with the control group. Insulin resistance was assessed using the homeostasis model of assessment of insulin resistance (HOMA-IR) and the homeostasis model of assessment of beta cell function. The FRS and the 10-year cardiovascular risk were compared between RA patients and controls. The presence of CAC was determined using electron-beam computed tomography, and the association between the FRS and CAC was examined. RESULTS: Significant differences in body mass index, waist circumference, rheumatoid factors (immunoglobulin [Ig]G, IgM and IgA) and inflammatory markers - C-reactive protein and erythrocyte sedimentation rate - were noted. There was significant correlation between HOMA-IR and body mass index, hypertension and C-reactive protein, but no correlation was seen with the homeostasis model of assessment of beta cell function. Significant differences were observed in the nontraditional biomarkers in RA patients, thus supporting their importance. Calcium deposition was observed in only seven RA patients. CONCLUSIONS: RA patients with increased C-reactive protein levels and erythrocyte sedimentation rates showed an increase in serum insulin levels and significant differences in HOMA-IR, thus indicating insulin resistance, which could lead to underlying progression of artherosclerosis. Significant differences were observed in the nontraditional risk factors, which could be chosen as biomarkers for endothelial dysfunction. There was a significant correlation between calcium score and the FRS in seven patients, suggestive of an underlying risk of atherosclerosis.

Regulation of urokinase expression at the posttranscription level by lung epithelial cells.

Urokinase-type plasminogen activator (uPA) is expressed by lung epithelial cells and regulates fibrin turnover and epithelial cell viability. PMA, LPS, and TNF-alpha, as well as uPA itself, induce uPA expression in lung epithelial cells. PMA, LPS, and TNF-alpha induce uPA expression through increased synthesis as well as stabilization of uPA mRNA, while uPA increases its own expression solely through uPA mRNA stabilization. The mechanism by which lung epithelial cells regulate uPA expression at the level of mRNA stability is unclear. To elucidate this process, we sought to characterize protein-uPA mRNA interactions that regulate uPA expression. Regulation of uPA at the level of mRNA stability involves the interaction of a ~40 kDa cytoplasmic-nuclear shuttling protein with a 66 nt uPA mRNA 3'UTR sequence. We purified the uPA mRNA 3'UTR binding protein and identified it as ribonucleotide reductase M2 (RRM2). We expressed recombinant RRM2 and confirmed its interaction with a specific 66 nt uPA 3'UTR sequence. Immunoprecipitation of cell lysates with anti-RRM2 antibody and RT-PCR for uPA mRNA confirmed that RRM2 binds to uPA mRNA. Treatment of Beas2B cells with uPA or LPS attenuated RRM2-endogenous uPA mRNA interactions, while overexpression of RRM2 inhibited uPA protein and mRNA expression through destabilization of uPA mRNA. LPS exposure of lung epithelial cells translocates RRM2 from the cytoplasm to the nucleus in a time-dependent manner, leading to stabilization of uPA mRNA. This newly recognized pathway could influence uPA expression and a broad range of uPA-dependent functions in lung epithelial cells in the context of lung inflammation and repair.

Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system.

Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition are associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine whether p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs of wild-type (WT) mice with BLM injury show increased apoptosis, p53, and PAI-1, and reciprocal suppression of uPA and uPA receptor (uPAR) protein expression. Treatment of WT mice with CSP reverses these effects and protects ATII cells against bleomycin (BLM)-induced apoptosis whereas CSP fails to attenuate ATII cell apoptosis or decrease p53 or PAI-1 in uPA-deficient mice. These mice demonstrate more severe PF. Thus p53 is increased and inhibits expression of uPA and uPAR while increasing PAI-1, changes that promote ATII cell apoptosis in mice with BLM-induced ALI. We show that CSP, an intervention targeting this pathway, protects the lung epithelium from apoptosis and prevents PF in BLM-induced lung injury via uPA-mediated inhibition of p53 and PAI-1.

Are the surgeons safe during UV-A radiation exposure in collagen cross-linking procedure?

PURPOSE: To quantify the effect of scattered UV-A radiation used in the collagen cross-linking (CXL) procedure and the amount of radiation reaching the surgeon and the surrounding area and to estimate the dampening effect by various protective devices. METHODS: In this case series, 3 patients [aged 25-30 (±2.5) years] with keratoconus underwent a CXL procedure with UV-A light and riboflavin. Irradiance was measured using a spectrometer (Model USB2000; Ocean Optics, Inc) for various distances from the source, at various angles, and for different durations of radiation. The spectrometer was also used to measure the dampening effect produced by gown, latex gloves, and UV-protective glasses. RESULTS: Maximum UV-A radiation (1.4 × 10(-9) mW/cm(2)) was measured at 2 cm from the limbus, when the probe was held at a 45-degree angle to the floor. UV-A radiation reaching the surgeon's eye and the abdomen was 3.403 × 10(-11) and 2.36 × 10(-11) mW/cm(2), respectively. Gown, latex gloves, and UV-protective glasses showed dampening effects of 99.58%, 95.01%, and 99.73%, respectively. CONCLUSIONS: CXL appears to be a safe procedure with respect to UV-A radiation exposure to the surgeon. Further safety can be ensured by UV-protective devices.