scholarly journals Local and Systemic Toxicity of Intraoral Submucosal Injections of Phentolamine Mesylate (OraVerse)

2009 ◽  
Vol 56 (4) ◽  
pp. 123-127 ◽  
Author(s):  
Bruce Rutherford ◽  
Jillynne R. Zeller ◽  
Daryl Thake
Keyword(s):  
Soft Tissues ◽  
Clinical Chemistry ◽  
Inferior Alveolar Nerve ◽  
Systemic Toxicity ◽  
Nerve Degeneration ◽  
Local Administration ◽  
Local Effects ◽  
Functional Deficits ◽  
Good Laboratory ◽  
Repeated Dosing

Abstract OraVerseTM, an injectable formulation of phentolamine mesylate (PM), was recently approved by the U.S. Food and Drug Administration (FDA) for reversal of anesthesia of the lip and tongue and associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. Because PM had not been approved previously for submucosal administration, 2 Good Laboratory Practices (GLP) studies in dogs designed to investigate systemic toxicity and the local effects of single and repeated dosing of OraVerse on the inferior alveolar nerve and branches of the superior alveolar nerve and adjacent soft tissues after local administration were conducted. Systemic toxicity was measured by preinjection and postinjection clinical examinations, clinical chemistry, and gross and microscopic examinations of major organs after necropsy. No evidence of systemic toxicity was detected. Local nerve and adjacent tissue damage was assessed by conventional histopathology. Nerve degeneration was evident in 1 animal. Mild perineural inflammation adjacent to the inferior alveolar nerve and inflammatory exudates were observed in submucosal tissues in several animals. No changes were observed in the nerves at injection sites of dogs from any dose group that were considered directly related to the test articles. These data reveal that single and repeated intraoral administrations of OraVerse are well tolerated in beagle dogs.

The effectiveness of early local administration of hyaluronic acid in experimental traumatic ischemia of the limb muscles

2021 ◽  
Author(s):  
A.V. Shulepov ◽  
I.A. Shperling ◽  
Yu.V. Yurkevich ◽  
N.V. Shperling
Keyword(s):  
Oxygen Consumption ◽  
Hyaluronic Acid ◽  
Oxygen Saturation ◽  
Wistar Rats ◽  
Soft Tissues ◽  
Local Administration ◽  
Compression Injury ◽  
Doppler Flowmetry ◽  
Muscle Ischemia ◽  
Male Wistar Rats

The experiments were performed on 280 male Wistar rats weighing 300-340 g. The design of the study included: modeling of compression injury of the soft tissues of the thigh, local injection of the preparation of hyaluronic acid "Gialift 3.5" into the area of damage 3 hours after the cessation of compression, taking into account the results after 7, 14 and 28 days. The introduction of hyaluronic acid into the area of compression injury of soft tissues reduces the severity of myoglobinemia, increases the immunohistochemical density of VEGF-positive cells, improves the perfusion characteristics of microcirculation, oxygen saturation, and specific oxygen consumption by tissues. Keywords: traumatic muscle ischemia, hyaluronic acid, myoglobin, microcirculation, metabolism, laser Doppler flowmetry, morphometry.

scholarly journals Necrotizing Soft Tissue Infections, the Challenge Remains

2021 ◽  
Vol 8 ◽  
Author(s):  
Femke Nawijn ◽  
Falco Hietbrink ◽  
Andrew B. Peitzman ◽  
Luke P. H. Leenen
Keyword(s):  
Soft Tissue ◽  
Critically Ill ◽  
Soft Tissues ◽  
Systemic Toxicity ◽  
The Other ◽  
Definitive Treatment ◽  
Critically Ill Patient ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Specific Symptoms

Background: Necrotizing Soft Tissue Infections (NSTIs) are uncommon rapidly spreading infection of the soft tissues for which prompt surgical treatment is vital for survival. Currently, even with sufficient awareness and facilities available, ambiguous symptoms frequently result in treatment delay.Objectives: To illustrate the heterogeneity in presentation of NSTIs and the pitfalls entailing from this heterogeneity.Discussion: NSTI symptoms appear on a spectrum with on one side the typical critically ill patient with fast onset and progression of symptoms combined with severe systemic toxicity resulting in severe physical derangement and sepsis. In these cases, the suspicion of a NSTI rises quickly. On the other far side of the spectrum is the less evident type of presentation of the patient with gradual but slow progression of non-specific symptoms over the past couple of days without clear signs of sepsis initially. This side of the spectrum is under represented in current literature and some physicians involved in the care for NSTI patients are still unaware of this heterogeneity in presentation.Conclusion: The presentation of a critically ill patient with evident pain out of proportion, erythema, necrotic skin and bullae is the classical presentation of NSTIs. On the other hand, non-specific symptoms without systemic toxicity at presentation frequently result in a battery of diagnostics tests and imaging before the treatment strategy is determined. This may result in a delay in presentation, delay in diagnosis and delay in definitive treatment. This failure to perform an adequate exploration expeditiously can result in a preventable mortality.

scholarly journals The Effect of Pre-cooling the Injection Site on Pediatric Pain Perception during the Administration of Local Anesthesia

2009 ◽  
Vol 10 (3) ◽  
pp. 43-50 ◽  
Author(s):  
Naser Asl Aminabadi ◽  
Ramin Mostofi Zadeh Farahani
Keyword(s):  
Injection Site ◽  
Local Anesthesia ◽  
Local Anesthetic ◽  
Pain Perception ◽  
Pediatric Patients ◽  
Soft Tissues ◽  
Inferior Alveolar Nerve ◽  
Topical Anesthesia ◽  
Pediatric Pain ◽  
Dental Procedures

Abstract Aim The aim of the study was to evaluate the effect of cooling the soft tissue of injection sites on the pain perceptions of pediatric patients during the administration of local anesthesia for routine dental procedures. Methods and Materials A total of 160 children aged 5-6 years were included in the present study. On a random basis, the subjects were allocated to the without ice pretreatment (WIP) group (topical anesthesia + counterstimulation + distraction) or the ice pretreatment (IP) group (cooling + topical anesthesia + counterstimulation + distraction). During the administration of an inferior alveolar nerve block, the children's behavior was assessed using the sound, eye, and motor (SEM) scale. The statistical analysis of data was performed based on the analysis of variance (ANOVA). Results There were no significant differences within the groups between the values of the sound, eye, and motor components for either the WIP or the IP groups (P>0.05). All three components of the SEM in the IP group were consistently lower than the WIP group (P<0.05). Moreover, the SEM value for the WIP group surpassed the IP group (P<0.05). Conclusions Cooling the site of infiltration block prior to the injection of local anesthesia significantly reduced the pain perceived during injection of local anesthetic agent in pediatric patients. Clinical Significance Pre-cooling of the soft tissues of an injection site prior to the administration of a local anesthetic can minimize the discomfort and anxiety associated with the injection procedure and facilitates the management of pediatric patients during this phase of a dental procedure. Citation Aminabadi NA, Farahani RMZ. The Effect of Pre-cooling the Injection Site on Pediatric Pain Perception during the Administration of Local Anesthesia. J Contemp Dent Pract 2009 May; (10)3:043-050.

scholarly journals Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies

2020 ◽  
Author(s):  
Shelagh Verco ◽  
Holly Maulhardt ◽  
Michael Baltezor ◽  
Emily Williams ◽  
Marc Iacobucci ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Systemic Toxicity ◽  
Local Administration ◽  
Submicron Particle ◽  
Tumor Cell Death ◽  
Primary Tumors ◽  
Clinical Investigations ◽  
Immune Mediated ◽  
Direct Cytotoxicity ◽  
Preclinical And Clinical Studies

Abstract This report describes local administration of submicron particle paclitaxel (SPP) (NanoPac®: ~ 800-nm-sized particles with high relative surface area with each particle containing ~ 2 billion molecules of paclitaxel) in preclinical models and clinical trials evaluating treatment of carcinomas. Paclitaxel is active in the treatment of epithelial solid tumors including ovarian, peritoneal, pancreatic, breast, esophageal, prostate, and non-small cell lung cancer. SPP has been delivered directly to solid tumors, where the particles are retained and continuously release the drug, exposing primary tumors to high, therapeutic levels of paclitaxel for several weeks. As a result, tumor cell death shifts from primarily apoptosis to both apoptosis and necroptosis. Direct local tumoricidal effects of paclitaxel, as well as stimulation of innate and adaptive immune responses, contribute to antineoplastic effects. Local administration of SPP may facilitate tumor response to systemically administered chemotherapy, targeted therapy, or immunotherapy without contributing to systemic toxicity. Results of preclinical and clinical investigations described here suggest that local administration of SPP achieves clinical benefit with negligible toxicity and may complement standard treatments for metastatic disease. Graphical abstract

Acute Toxicity Evaluation of Proliferol: A Dose-Escalating, Placebo-Controlled Study in Swine

2009 ◽  
Vol 28 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Simon Dagenais ◽  
James Wooley ◽  
Mark Hite ◽  
Robert Green ◽  
John Mayer
Keyword(s):  
Soft Tissues ◽  
Clinical Chemistry ◽  
Clinical Results ◽  
Skeletal Muscle Regeneration ◽  
Controlled Study ◽  
Miniature Swine ◽  
Clinical Observations ◽  
Urine Concentrations ◽  
The Many ◽  
Connective Tissue Repair

Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1×), medium (5×), or high (10×) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.

scholarly journals Biocompatibility studies on cerium oxide nanoparticles – combined study for local effects, systemic toxicity and genotoxicity via implantation route

2019 ◽  
Vol 8 (1) ◽  
pp. 25-37 ◽  
Author(s):  
V. Kalyanaraman ◽  
Sangeetha Vasudevaraj Naveen ◽  
N. Mohana ◽  
R. M. Balaje ◽  
K. R. Navaneethakrishnan ◽  
...  
Keyword(s):  
Cerium Oxide ◽  
Systemic Toxicity ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Local Effects

Cerium oxide nanoparticles showed negligible local effects, low systemic toxicity and genotoxicity via implantation route.

Subchronic Dermal Toxicity and Oral Neurotoxicity of Triethylene Glycol Monomethyl Ether in Cd Rats

1998 ◽  
Vol 17 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Michael W. Gill ◽  
Edward H. Fowler ◽  
Ralph Gingell ◽  
Larry G. Lomax ◽  
Richard A. Corley
Keyword(s):  
Environmental Protection Agency ◽  
Clinical Chemistry ◽  
Triethylene Glycol ◽  
Monomethyl Ether ◽  
Systemic Toxicity ◽  
Peroral Administration ◽  
High Dose ◽  
Dermal Toxicity ◽  
Glycol Monomethyl Ether ◽  
Dose Levels

These studies were conducted to evaluate the potential for repeated subchronic administration of triethylene glycol monomethyl ether (TGME) to produce systemic toxicity in the rat following dermal application, and neurotoxicity in the rat following peroral administration. The route of administration and maximum dose levels for these studies were specified by the U.S. Environmental Protection Agency (EPA) in a testing consent order for TGME. In the subchronic dermal toxicity study, TGME (undiluted) was applied to the clipped backs of CD rats (10 rats/sex/group) for 6 h/day (occluded), 5 days/wk or 13 wk at dose levels of 0, 0.4, 1.2, and 4.0 g/kg/day. Four groups of satellite animals (5 rats/sex/group) employed for interim hematology and clinical chemistry measurements were dosed in the same manner for 31 days. Experimental evaluations included clinical examinations, food consumption, body weight, ophthalmology, estrous cyclicity, hematology, clinical chemistry, urinalysis, and necropsy for all animals and microscopic examination of a complete set of tissues (including bone marrow smears) for animals in the control and high-dose treatment groups. In addition, the testes and epididymides were processed for examination of spermatocyte development. None of the experimental endpoints included in this study to evaluate the potential for systemic toxicity were affected by treatment with TGME. For the neurotoxicity study, TGME was mixed in the drinking water and administered ad libitum to rats

Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats

2000 ◽  
Vol 19 (12) ◽  
pp. 684-692 ◽  
Author(s):  
B Gonzalez ◽  
A Casaco ◽  
P Alvarez ◽  
M Leon ◽  
M Arteaga ◽  
...  
Keyword(s):  
Growth Factor ◽  
Behavioral Problems ◽  
Clinical Chemistry ◽  
Growth Factor Receptor ◽  
Systemic Toxicity ◽  
Intraventricular Administration ◽  
Intracerebral Administration ◽  
Histopathological Studies ◽  
The Right ◽  
Toxicity Effects

Brain tumors are often incurable despite current aggressive treatmentmodalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h 3 is a humanized antiepidemal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re 3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5-II dose (2.5 pl into the left and 2.5 MI into the right lateral ventricles) of neutral solution containing50pgofh-R31abeledwith49.5 t 1.7,284±13.7or 579±23.7 p Ci of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Bodyweights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re 3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevetheless, further studies are necessary to discard learning and behavioral problems.

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