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1.
Prehosp Emerg Care ; 28(2): 363-368, 2024.
Article in English | MEDLINE | ID: mdl-36692384

ABSTRACT

INTRODUCTION: In response to the COVID-19 pandemic, emergency medical services (EMS) and hospitals recognized the need for innovative programs addressing 9-1-1 utilization and ambulance transport to provide patient-centered, safe, cost-effective care. The ET3 (Emergency Triage, Treatment, and Transport) model provides flexibility and new payments to ambulance care teams for Medicare beneficiaries for alternate strategies of care. This includes providing treatment in place through telehealth after a 9-1-1 call and ambulance response. Our objective is to evaluate the implementation barriers of a telemedicine service to 9-1-1 responding ambulances providing treatment in place for low-acuity conditions. METHODS: The TeleEMS program was piloted in a large, urban fire-based EMS system with eight ambulances geographically surrounding one hospital. Paramedics received training on the telemedicine software and screening criteria, which were age 1-70 and vital sign parameters. Pregnant, combative, and patients with no clear need for emergency department transport were excluded. Three emergency physicians with additional training in EMS provided the TeleEMS service from 8am to 6 pm on Monday - Friday. The telemedicine software was application-based and provided HIPAA-compliant two-way, real-time audio and video communication through the 4G network on a tablet. The TeleEMS physicians had access to a database of clinics and hospitals that coordinate health care. The TeleEMS physician contacted the patient within 24-72 hours after the encounter for follow-up. RESULTS: The TeleEMS pilot program ran for 12 weeks from April - June 2021. During this time, there were seven completed consults with treatment in place, one completed consult with transport to an emergency department, and five consult attempts that failed due to technological issues with resultant transport. Each of the consults (13/13) met the TeleEMS screening criteria. Post-pilot focus group sessions were held to determine paramedic feedback. Barriers to an EMS telemedicine program include paramedic buy-in, patient expectations for emergency care, technology limitations, and qualified physician resources. CONCLUSIONS: An EMS telemedicine program can be successfully implemented in urban fire-based EMS systems for 9-1-1 responding ambulances. Barriers to implementation should be addressed at the paramedic, patient, technology, and program levels to improve success.


Subject(s)
Emergency Medical Services , Telemedicine , Aged , Humans , United States , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Pilot Projects , Pandemics , Medicare
2.
Prehosp Emerg Care ; 27(3): 356-359, 2023.
Article in English | MEDLINE | ID: mdl-35200091

ABSTRACT

BACKGROUND: Prehospital hypoglycemia is usually treated with oral or intravenous (IV) dextrose in a variety of concentrations. In the absence of vascular access, intramuscular (IM) glucagon is commonly administered. Occupational needle-stick injury remains a significant risk while attempting to obtain vascular access or administer medications intramuscularly in the prehospital setting. We sought to determine if intranasal (IN) glucagon is effective in the prehospital treatment of hypoglycemia. METHODS: We performed a retrospective analysis of all consecutive cases where recombinant glucagon was administered IN by paramedics from January 1, 2015 through December 31, 2020. Excluded were cases without pre or post administration blood glucose documentation, and cases where another form of treatment for hypoglycemia was administered at any time during the EMS encounter. The primary outcome was clinical response to IN glucagon documented by paramedics; secondary outcomes included pre and post administration blood glucose values. RESULTS: Out of 44 cases that met study inclusion criteria, 14 patients (32%) had substantial improvement, 13 patients (30%) had slight improvement, and 17 patients (38%) had no improvement in mental status after administration of IN glucagon. In cases with substantial improvement (n = 14), the mean pre administration blood glucose was 33.8 mg/dl and the mean post administration blood glucose was 87.1 mg/dl (mean increase 53.3 mg/dl, 95% CI: 21.5 to 85.1). In cases with slight improvement (n = 13), the mean pre administration blood glucose was 23.9 mg/dl and the mean post administration blood glucose was 53.8 mg/dl (mean increase 29.9 mg/dl, 95% CI = 2.9 to 56.9). In case with no improvement (n = 17) the mean pre administration blood glucose was 30.1 mg/dl and the mean post administration glucose was 33.1 mg/dl (mean difference 3.1 mg/dl, 95% CI: -10.1 to 3.9). CONCLUSION: Intranasal administration of recombinant glucagon for hypoglycemia resulted in a clinically significant improvement in mental status and a corresponding increase in blood glucose levels in select cases in the prehospital setting.


Subject(s)
Emergency Medical Services , Hypoglycemia , Humans , Glucagon/therapeutic use , Blood Glucose/analysis , Administration, Intranasal , Retrospective Studies , Emergency Medical Services/methods , Hypoglycemia/drug therapy , Hypoglycemia/complications
3.
West J Emerg Med ; 21(3): 677-683, 2020 Apr 21.
Article in English | MEDLINE | ID: mdl-32421519

ABSTRACT

INTRODUCTION: Agitated patients in the prehospital setting pose challenges for both patient care and emergency medical services (EMS) provider safety. Midazolam is frequently used to control agitation in the emergency department setting; however, limited data exist in the prehospital setting. We describe our experience treating patients with midazolam for behavioral emergencies in a large urban EMS system. We hypothesized that using midazolam for acute agitation leads to improved clinical conditions without causing significant clinical deterioration. METHODS: We performed a retrospective review of EMS patient care reports following implementation of a behavioral emergencies protocol in a large urban EMS system from February 2014-June 2016. For acute agitation, paramedics administered midazolam 1 milligram (mg) intravenous (IV), 5 mg intramuscular (IM), or 5 mg intranasal (IN). Results were analyzed using descriptive statistics, Levene's test for assessing variance among study groups, and t-test to evaluate effectiveness based on route. RESULTS: In total, midazolam was administered 294 times to 257 patients. Median age was 30 (interquartile range 24-42) years, and 66.5% were male. Doses administered were 1 mg (7.1%) and 5 mg (92.9%). Routes were IM (52.0%), IN (40.8%), and IV (7.1%). A second dose was administered to 37 patients. In the majority of administrations, midazolam improved the patient's condition (73.5%) with infrequent adverse events (3.4%). There was no significant difference between the effectiveness of IM and IN midazolam (71.0% vs 75.4%; p = 0.24). CONCLUSION: A midazolam protocol for prehospital agitation was associated with reduced agitation and a low rate of adverse events.


Subject(s)
Emergency Medical Services/methods , Hypnotics and Sedatives/administration & dosage , Mental Disorders/drug therapy , Midazolam/administration & dosage , Administration, Intranasal , Administration, Intravenous , Adult , Allied Health Personnel , Clinical Protocols , Dose-Response Relationship, Drug , Drug Administration Schedule , Emergencies , Female , Humans , Hypnotics and Sedatives/therapeutic use , Injections, Intramuscular , Male , Midazolam/therapeutic use , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
5.
Prehosp Emerg Care ; 22(3): 312-318, 2018.
Article in English | MEDLINE | ID: mdl-29297717

ABSTRACT

OBJECTIVE: Accurate prehospital identification of patients with acute ischemic stroke (AIS) from large vessel occlusion (LVO) facilitates direct transport to hospitals that perform endovascular thrombectomy. We hypothesize that a cut-off score of the Cincinnati Prehospital Stroke Scale (CPSS), a simple assessment tool currently used by emergency medical services (EMS) providers, can be used to identify LVO. METHODS: Consecutively enrolled, confirmed AIS patients arriving via EMS between August 2012 and April 2014 at a high-volume stroke center in a large city with a single municipal EMS provider agency were identified in a prospective, single-center registry. Head and neck vessel imaging confirmed LVO. CPSS scores were abstracted from prehospital EMS records. Spearman's rank correlation, Wilcoxon rank-sum test, and Student's t-test were performed. Cohen's kappa was calculated between CPSS abstractors. The Youden index identified the optimal CPSS cut-off. Multivariate logistic regression controlling for age, sex, and race determined the odds ratio (OR) for LVO. RESULTS: Of 144 eligible patients, 138 (95.8%) had CPSS scores in the EMS record and were included for analysis. The median age was 69 (IQR 58-81) years. Vessel imaging was performed in 97.9% of patients at a median of 5.9 (IQR 3.6-10.2) hours from hospital arrival, and 43.7% had an LVO. Intravenous tissue plasminogen activator was administered to 29 patients, in whom 12 had no LVO on subsequent vessel imaging. The optimal CPSS cut-off predicting LVO was 3, with a Youden index of 0.29, sensitivity of 0.41, and specificity of 0.88. The adjusted OR for LVO with CPSS = 3 was 5.7 (95% CI 2.3-14.1). Among patients with CPSS = 3, 72.7% had an LVO, compared with 34.3% of patients with CPSS ≤ 2 (p < 0.0001). CONCLUSIONS: A CPSS score of 3 reliably identifies LVO in AIS patients. EMS providers may be able to use the CPSS, a simple, widely adopted prehospital stroke assessment tool, with a cut-off score to screen for patients with suspected LVO.


Subject(s)
Arterial Occlusive Diseases/diagnosis , Brain Ischemia/physiopathology , Emergency Medical Services , Stroke/physiopathology , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Registries , Retrospective Studies , Tissue Plasminogen Activator/administration & dosage
6.
Prehosp Emerg Care ; 21(6): 761-766, 2017.
Article in English | MEDLINE | ID: mdl-28661784

ABSTRACT

OBJECTIVES: Identifying stroke during a 9-1-1 call is critical to timely prehospital care. However, emergency medical dispatchers (EMDs) recognize stroke in less than half of 9-1-1 calls, potentially due to the words used by callers to communicate stroke signs and symptoms. We hypothesized that callers do not typically use words and phrases considered to be classical descriptors of stroke, such as focal neurologic deficits, but that a mixed-methods approach can identify words and phrases commonly used by 9-1-1 callers to describe acute stroke victims. METHODS: We performed a mixed-method, retrospective study of 9-1-1 call audio recordings for adult patients with confirmed stroke who were transported by ambulance in a large urban city. Content analysis, a qualitative methodology, and computational linguistics, a quantitative methodology, were used to identify key words and phrases used by 9-1-1 callers to describe acute stroke victims. Because a caller's level of emotional distress contributes to the communication during a 9-1-1 call, the Emotional Content and Cooperation Score was scored by a multidisciplinary team. RESULTS: A total of 110 9-1-1 calls, received between June and September 2013, were analyzed. EMDs recognized stroke in 48% of calls, and the emotional state of most callers (95%) was calm. In 77% of calls in which EMDs recognized stroke, callers specifically used the word "stroke"; however, the word "stroke" was used in only 38% of calls. Vague, non-specific words and phrases were used to describe stroke victims' symptoms in 55% of calls, and 45% of callers used distractor words and phrases suggestive of non-stroke emergencies. Focal neurologic symptoms were described in 39% of calls. Computational linguistics identified 9 key words that were more commonly used in calls where the EMD identified stroke. These words were concordant with terms identified through qualitative content analysis. CONCLUSIONS: Most 9-1-1 callers used vague, non-specific, or distractor words and phrases and infrequently provide classic stroke descriptions during 9-1-1 calls for stroke. Both qualitative and quantitative methodologies identified similar key words and phrases associated with accurate EMD stroke recognition. This study suggests that tools incorporating commonly used words and phrases could potentially improve EMD stroke recognition.


Subject(s)
Communication , Emergency Medical Service Communication Systems , Stroke/diagnosis , Adult , Aged , Ambulances , Emergency Medical Services , Female , Humans , Male , Middle Aged , Retrospective Studies , Stroke/complications , Stroke/psychology
7.
Prehosp Emerg Care ; 21(5): 610-615, 2017.
Article in English | MEDLINE | ID: mdl-28481722

ABSTRACT

OBJECTIVE: Despite the value of out-of-hospital Termination of Resuscitation (TOR) and the scientific evidence in favor of this practice, TOR has not been uniformly adopted or consistently practiced in EMS systems. Previous focus group studies have identified multiple barriers to implementation of out of hospital TOR but existing literature on EMS provider perceptions is limited. We sought to identify EMS providers' perceived barriers to performing out-of-hospital TOR in a large urban EMS system. METHODS: The Chicago EMS System is a regional collaborative of EMS physicians, nurses and provider agencies, including the Chicago Fire Department (CFD), which provides exclusive emergency response for 9-1-1 calls in Chicago. CFD is an urban, fire-based EMS agency with a tiered response, with fire-fighter EMTs and paramedics providing initial care, and single role paramedics providing supplemental care and transport. A 2-page written survey was distributed to understand providers' experiences with managing OHCA and perceived barriers to TOR to inform subsequent improvements in protocol development and education. RESULTS: Of 3500 EMS providers that received the survey, 2309 were completed (66%). Survey respondent demographics were fire-fighter/EMTB (69%), fire-fighter/paramedic (14%), and single role paramedic (17%). The most frequent barrier to field TOR was scene safety (86%). The most common safety issue identified was family reaction to TOR (68%) and many providers felt threatened by family when trying to perform TOR (38%). Providers with a higher career numbers of OHCA were more likely to have felt threatened by the family (OR 6.70, 95% CI 2.99-15.00) and single role paramedics were more likely than FF/EMTBs to have felt threatened (OR 3.34, 95% CI 2.65-4.22). Barriers to delivering a death notification after TOR, include being uncomfortable or threatened with possible family reaction (52%) and family asking to continue the resuscitation (45%). There was lack of formal prior death notification training, the majority learned from colleagues through on the job training. CONCLUSIONS: Our study identifies scene safety, death notification delivery, and lack of formal training in death notification as barriers that EMS providers face while performing TOR in a large urban EMS system. These findings informed educational and operational initiatives to overcome the identified provider level issues and improve compliance with TOR policies.


Subject(s)
Attitude of Health Personnel , Cardiopulmonary Resuscitation/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Emergency Responders/psychology , Out-of-Hospital Cardiac Arrest/therapy , Withholding Treatment/statistics & numerical data , Chicago , Focus Groups , Humans , Physicians , Surveys and Questionnaires , Urban Health Services
8.
Am J Emerg Med ; 31(4): 717-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23380114

ABSTRACT

BACKGROUND: Snorting or smoking heroin is a known trigger of acute asthma exacerbation. Heroin abuse may be a risk factor for more severe asthma exacerbations and intubation. Heroin and other opioids provoke pulmonary bronchoconstriction. Naloxone may play a role in decreasing opioid-induced bronchospasm. There are no known clinical cases describing the effect of naloxone on opioid-induced bronchospasm. METHODS: This is an observational study in which nebulized naloxone was administered to patients with suspected heroin-induced bronchospasm. Patients with spontaneous respirations were administered 2 mg of naloxone with 3 mL of normal saline by nebulization. We describe a case series of administrations for suspected heroin-induced bronchospasm. RESULTS: We reviewed 21 administrations of nebulized naloxone to patients with suspected heroin-induced bronchospasm. Of these, 19 patients had a clinical response to treatment documented. Thirteen patients displayed clinical improvement (68%), 4 patients had no improvement (21%), and 2 patients worsened (10%). Of the 2 patients who had clinical decline, none required intubation. Of the patients who improved, 1 patient received only nebulized naloxone and 1 patient received naloxone and albuterol together. Seven patients showed clinical improvement after the administration of albuterol, atrovent, and naloxone together as a combination. Four patients showed additional improvement when the naloxone was administered after the albuterol and atrovent combination. CONCLUSION: Naloxone may play a role in reducing acute opioid-induced bronchoconstriction, either alone or in combination with albuterol. Future controlled studies should be conducted to determine if the addition of naloxone to standard treatment improves bronchospasm without causing adverse effects.


Subject(s)
Bronchial Spasm/drug therapy , Heroin/adverse effects , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Narcotics/adverse effects , Administration, Inhalation , Bronchial Spasm/chemically induced , Humans , Treatment Outcome
9.
Prehosp Emerg Care ; 16(2): 289-92, 2012.
Article in English | MEDLINE | ID: mdl-22191727

ABSTRACT

BACKGROUND: Emergency medical services (EMS) traditionally administer naloxone using a needle. Needleless naloxone may be easier when intravenous (IV) access is difficult and may decrease occupational blood-borne exposure in this high-risk population. Several studies have examined intranasal naloxone, but nebulized naloxone as an alternative needleless route has not been examined in the prehospital setting. OBJECTIVE: We sought to determine whether nebulized naloxone can be used safely and effectively by prehospital providers for patients with suspected opioid overdose. METHODS: We performed a retrospective analysis of all consecutive cases administered nebulized naloxone from January 1 to June 30, 2010, by the Chicago Fire Department. All clinical data were entered in real time into a structured EMS database and data abstraction was performed in a systematic manner. Included were cases of suspected opioid overdose, altered mental status, and respiratory depression; excluded were cases where nebulized naloxone was given for opioid-triggered asthma and cases with incomplete outcome data. The primary outcome was patient response to nebulized naloxone. Secondary outcomes included need for rescue naloxone (IV or intramuscular), need for assisted ventilation, and adverse antidote events. Kappa interrater reliability was calculated and study data were analyzed using descriptive statistics. RESULTS: Out of 129 cases, 105 met the inclusion criteria. Of these, 23 (22%) had complete response, 62 (59%) had partial response, and 20 (19%) had no response. Eleven cases (10%) received rescue naloxone, no case required assisted ventilation, and no adverse events occurred. The kappa score was 0.993. CONCLUSION: Nebulized naloxone is a safe and effective needleless alternative for prehospital treatment of suspected opioid overdose in patients with spontaneous respirations.


Subject(s)
Analgesics, Opioid/poisoning , Emergency Medical Services/methods , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Administration, Inhalation , Adolescent , Adult , Aged , Cohort Studies , Drug Overdose/drug therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Opioid-Related Disorders/drug therapy , Retrospective Studies , Risk Assessment , Safety Management , Treatment Outcome , Young Adult
10.
Methods Mol Med ; 131: 251-5, 2007.
Article in English | MEDLINE | ID: mdl-17656788

ABSTRACT

All adenoviruses (Ads) sequenced so far encode a single endopeptidase of the cysteine class, named adenain. The Ad2 adenain is a 204-residue, nearly inactive monomer, which is activated during virus maturation by an 11-residue cleavage fragment of capsid protein pVI. This chapter describes the synthesis, purification, activation, and assay of recombinant human Ad type adenain.


Subject(s)
Adenoviridae/enzymology , Peptide Hydrolases/biosynthesis , Chromatography, Liquid , HeLa Cells , Humans , Peptide Hydrolases/chemistry , Peptide Hydrolases/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism
12.
J Emerg Med ; 27(2): 139-42, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15261355

ABSTRACT

Takayasu's arteritis (TA) is a vasculitis involving the aorta and its branches. We report a case of undiagnosed TA that presented to the Emergency Department with a chief complaint of chest pain and signs consistent with an aortic dissection.


Subject(s)
Aortic Aneurysm, Thoracic/diagnosis , Aortic Dissection/diagnosis , Takayasu Arteritis/diagnosis , Acute Disease , Adrenal Cortex Hormones/therapeutic use , Aortic Dissection/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortography , Chest Pain/etiology , Diagnosis, Differential , Emergency Service, Hospital , Female , Humans , Middle Aged , Takayasu Arteritis/complications , Takayasu Arteritis/diagnostic imaging , Takayasu Arteritis/drug therapy , Treatment Outcome
13.
Acta Microbiol Immunol Hung ; 50(1): 95-101, 2003.
Article in English | MEDLINE | ID: mdl-12793204

ABSTRACT

With the possible exception of very simple viruses, most viruses appear to encode at least one virus specific endopeptidase. In addition to facilitating the orchestrated fragmentation of polyproteins of RNA viruses, these proteolytic enzymes may also be involved in the suppression of host protein synthesis, the regulation of virus assembly, the egress and subsequent uncoating in another cycle of infection of both RNA and DNA viruses. The endopeptidase encoded by adenoviruses (AVP or adenain) appears to be involved in several of these functions. Most of the literature concerns the protease of human adenovirus type 2, but there are good reasons to believe that the proteases of other adenovirus serotypes will be very similar. For a review see Weber [1,2].


Subject(s)
Adenoviridae/enzymology , Cysteine Endopeptidases/metabolism , Adenoviridae/drug effects , Adenoviridae Infections/virology , Adenoviruses, Human/drug effects , Adenoviruses, Human/enzymology , Animals , Antiviral Agents/pharmacology , Cattle , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Cysteine Proteinase Inhibitors/pharmacology , Dogs , Humans , Viral Proteins/metabolism
14.
Antiviral Res ; 58(2): 167-73, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12742577

ABSTRACT

Green tea catechins have been reported to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV. To date there are no effective anti-adenoviral therapies. Consequently, we studied the effect of green tea catechins, and particularly the predominant component, epigallocatechin-3-gallate (EGCG), on adenovirus infection and the viral protease adenain, in cell culture. Adding EGCG (100 microM) to the medium of infected cells reduced virus yield by two orders of magnitude, giving and IC(50) of 25 microM and a therapeutic index of 22 in Hep2 cells. The agent was the most effective when added to the cells during the transition from the early to the late phase of viral infection suggesting that EGCG inhibits one or more late steps in virus infection. One of these steps appears to be virus assembly because the titer of infectious virus and the production of physical particles was much more affected than the synthesis of virus proteins. Another step might be the maturation cleavages carried out by adenain. Of the four catechins tested on adenain, EGCG was the most inhibitory with an IC(50) of 109 microM, compared with an IC(50) of 714 microM for PCMB, a standard cysteine protease inhibitor. EGCG and different green teas inactivated purified adenovirions with IC(50) of 250 and 245-3095, respectively. We conclude that the anti-adenoviral activity of EGCG manifests itself through several mechanisms, both outside and inside the cell, but at effective drug concentrations well above that reported in the serum of green tea drinkers.


Subject(s)
Adenoviridae/drug effects , Antiviral Agents/pharmacology , Catechin/analogs & derivatives , Catechin/pharmacology , Cysteine Endopeptidases/metabolism , Enzyme Inhibitors/pharmacology , Tea , Adenoviridae/enzymology , Adenoviridae/physiology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Humans , Inhibitory Concentration 50 , Tea/chemistry , Virion/drug effects , Virus Replication/drug effects
15.
Virus Res ; 89(1): 41-52, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12367749

ABSTRACT

The adenovirus protease, adenain is functionally required for virion uncoating and virion maturation and release from the infected cell. In addition to hydrolysis of precursor proteins at specific consensus sites, adenain has also been observed to cleave viral proteins at other sites. Here we re-examine the sequences in the consensus sites and also the phenomena of cleavage at other sites on viral proteins II, 100K, V, VI and VII. An examination of the eight residues flanking the scissile bond in 274 consensus sites from 36 different adenovirus serotypes in the DNA sequence databanks provided the following main conclusions: (1) two types of consensus sites, type 1, (M,I,L)XGX-G and type 2, (M,I,L)XGG-X, (2) the variant positions P(3) and P(1) never contained C,P,D,H,W,Y and C,P,G,M amino acids, respectively in type 1, (3) the variant positions P(3) and P(1)' never contained C,D,L,W and C,P,D,Q,H,Y,W amino acids, respectively in type 2, and (4) the thiol forming C residue occurred only twice within the eight residues flanking the scissile bond and that in the P(4)' position. Six unusual serotypes had (M,L,I)XAT-G as the PVII consensus site. Adenain has been proposed to cleave protein VI at an unknown site in the course of virion uncoating. The cleavage of capsid protein VI in the absence of a consensus site is confirmed here in vitro using recombinant adenain. Virion proteins II, V and VII and the nonstructural protein 100K were also digested in vitro into discrete fragments by recombinant adenain. We conclude that adenain preferentially cleaves viral proteins at their consensus sites, but is capable, in vitro of cleavages at other discrete sites which resemble the consensus cleavage sites.


Subject(s)
Adenoviruses, Human/enzymology , Cysteine Endopeptidases/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism , Adenoviruses, Human/genetics , Cell Line , Cysteine Endopeptidases/genetics , Humans , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Substrate Specificity
16.
Photochem Photobiol Sci ; 1(4): 246-54, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12661964

ABSTRACT

Research efforts have focused on the improvement of already established photodynamic therapy (PDT) protocols. The use of adjunct therapies is one such route. The integrin class of receptors mediates extracellular matrix signals through a complex maze of intertwining cellular pathways. The Arg-Gly-Asp (RGD) motif is known to bind to several of the 25 known integrin receptor types. Soluble RGD peptides under most circumstances induce apoptosis in a number of cell lines In this study, the effect of an RGD-containing peptide on the photodynamic action of aluminium disulfophthalocyanine (A1PcS(2adj)) was investigated. Adenocarcinoma lung cancer cells (A549) and murine mammary cancer cells (EMT-6) were treated with A1PcS(2adj) in the presence of soluble RGD. At elevated RGD concentrations (10 mM) apoptosis was induced by the peptide alone. It was shown that at lower concentrations, RGD abrogated the apoptotic effect of PDT in both cell lines, as assessed by an MTT cytotoxicity assay, nucleosomal DNA laddering and the formation of apoptotic bodies. RGD protection against apoptosis was more pronounced in the A549 receptor positive cell line which exhibits over 70% cell survival when using 100 microM RGD peptide under LD90 conditions. Different parameters were investigated to clearly establish that the attenuation of cell killing was not solely due to quenching of the excited species by the peptide. Indeed, the phenomenon is not photophysical but biological.


Subject(s)
Oligopeptides/chemistry , Peptides/pharmacology , Humans , Microscopy, Fluorescence , Oxidation-Reduction , Peptides/chemistry , Singlet Oxygen , Tumor Cells, Cultured
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