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Chrysotherapy: a synoptic review

Chrysotherapy--the treatment of rheumatoid arthritis (RA) patients with monovalent gold drugs possessing anti-inflammatory and other properties--has been used with some success for more than 70 years; however, the metabolites generated from gold drugs have not been identified positively and the mechanisms of action are not known with certainty. This account selectively reviews recent available literature on the history of gold in medicine, with emphasis on RA; the role of Au+ and Au+ metabolites (Au(CN)2-, Au+3, Auo) and other mechanisms in chrysotherapy; current treatment regimes for RA using gold drugs; chrysotherapy case histories based on 2166 RA patients; and adverse effects of chrysotherapy, mainly various forms of dermatitis. More research seems needed on the role of gold metabolites in the treatment of RA, the use of more sensitive and uniform indicators of treatment success, improved routes of drug administration for maximum efficacy, and the development of gold drugs with minimal side effects.

Inflammation Research

Effects of harmful algal blooms on amphibians and reptiles are under-reported and under-represented

Harmful algal blooms (HABs) are a persistent and increasing problem globally, yet we still have limited knowledge about how they affect wildlife. Although semi-aquatic and aquatic amphibians and reptiles have experienced large declines and occupy environments where HABs are increasingly problematic, their vulnerability to HABs remains unclear. To inform monitoring, management, and future research, we conducted a literature review, synthesized the studies, and report on the mortality events describing effects of cyanotoxins from HABs on freshwater herpetofauna. Our review identified 37 unique studies and 71 endpoints (no-observed-effect and lowest-observed-effect concentrations) involving 11 amphibian and 3 reptile species worldwide. Responses varied widely among studies, species, and exposure concentrations used in experiments. Concentrations causing lethal and sublethal effects in laboratory experiments were generally 1 to 100 µg/L, which contains the mean value of reported HAB events but is 70 times less than the maximum cyanotoxin concentrations reported in the environment. However, one species of amphibian was tolerant to concentrations of 10,000 µg/L, demonstrating potentially immense differences in sensitivities. Most studies focused on microcystin-LR (MC-LR), which can increase systemic inflammation and harm the digestive system, reproductive organs, liver, kidneys, and development. The few studies on other cyanotoxins illustrated that effects resembled those of MC-LR at similar concentrations, but more research is needed to describe effects of other cyanotoxins and mixtures of cyanotoxins that commonly occur in the environment. All experimental studies were on larval and adult amphibians; there were no such studies on reptiles. Experimental work with reptiles and adult amphibians is needed to clarify thresholds of tolerance. Only nine mortality events were reported, mostly for reptiles. Given that amphibians likely decay faster than reptiles, which have tissues that resist decomposition, mass amphibian mortality events from HABs have likely been under-reported. We propose that future efforts should be focused on seven major areas, to enhance our understanding of effects and monitoring of HABs on herpetofauna that fill important roles in freshwater and terrestrial environments. Environ Toxicol Chem 2024;00:1–14. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Environmental Toxicology and Chemistry

Mortality of captive whooping cranes caused by eastern equine encephalitis virus

Of 39 captive whooping cranes (Grus americana), 7 died during a 7-week period (Sept 17 through Nov 4, 1984) at the Patuxent Wildlife Research Center, Laurel, Md. Before their deaths, 4 cranes did not develop clinical signs, whereas the other 3 cranes were lethargic and ataxic, with high aspartate transaminase, gamma-glutamyl transferase, and lactic acid dehydrogenase activities, and high uric acid concentrations. Necropsies indicated that the birds had ascites, intestinal mucosal discoloration, fat depletion, hepatomegaly, splenomegaly, and visceral gout. Microscopically, extensive necrosis and inflammation were seen in many visceral organs; the CNS was not affected. Eastern equine encephalitis (EEE) virus was isolated from specimens of the livers, kidneys, lungs, brains, and intestines of 4 of the 7 birds that died, and EEE virus-neutralizing antibody was detected in 14 (44%) of the 32 surviving birds. Other infectious or toxic agents were not found. Morbidity or mortality was not detected in 240 sandhill cranes (Grus canadensis) interspersed among the whooping cranes; however, 13 of the 32 sandhill cranes evaluated had EEE virus-neutralizing antibody. Of the 41 wild birds evaluated in the area, 3 (4%) had EEE virus-neutralizing antibody. Immature Culiseta melanura (the most probable mosquito vector) were found in scattered foci 5 km from the research center.

Maryland

Effects of chronic ingestion of South Louisiana crude oil on mallard ducklings

South Louisiana crude oil was fed to duckling mallards (Anas platyrhynchos) in concentrations of 0.025, 0.25, 2.5, and 5.0% of the diet from hatching to 8 weeks of age to assess the effects of chronic oil ingestion during early development. Growth was depressed in birds receiving a diet containing 5% oil but there was no oil-related mortality. Diets containing 0.25, 2.5, and 5.0% oil impaired avoidance behavior of 6-day-old mallard ducklings when compared with controls or ducklings fed 0.025% oil, but had no effect on open-field behavior of 7-day-old ducklings. Liver hypertrophy and splenic atrophy were gross evidence of the pathological effects of oil in birds on the 2.5 and 5.0% oil diets. Biochemical lesions that occurred included elevation of plasma alanine aminotransferase and ornithine carbamyl transferase activity. Hepatocyte hypertrophy and bile duct proliferation in the liver were noted in birds fed the 2.5 and 5.0% oil diets and tubular inflammation and degeneration in the kidney were noted in birds fed the 5.0% oil diet.

Environmental Research

Aphanomyces invadans in Atlantic Menhaden along the East Coast of the United States

The cause of deeply penetrating ulcers of Atlantic menhaden Brevoortia tyrannus has been the subject of significant research efforts in recent years. These lesions and the associated syndrome termed ulcerative mycosis have been observed along the East Coast of the United States since at least the early 1980s. Although Aphanomyces spp. were isolated from these lesions in the mid to late 1980s, similar lesions could not be reproduced by experimental infections of Atlantic menhaden with these isolates. The identical characteristic histologic appearance of granulomatous inflammation surrounding the penetrating fungal hyphae occurs in fish with epizootic ulcerative syndrome (EUS), as reported throughout South Asia, Japan, and Australia. Aphanomyces invadans has been found to be the causative agent of EUS in all of these countries. Using methods developed for the study of EUS, we successfully isolated an organism for which the DNA sequence, morphology, temperature and salinity growth characteristics, and infectivity of chevron snakehead Channa striata are identical to A. invadans . Using the polymerase chain reaction assay for A. invadans , we were able to demonstrate the presence of the organism from Atlantic menhaden lesions collected in U.S. estuarine waters from Delaware to South Carolina. In addition, the organism was present in lesions on a bluegill Lepomis macrochirus from a farm pond in Georgia and channel catfish Ictalurus punctatus from a farm pond in Louisiana.

Maryland

Monitoring oral temperature, heart rate, and respiration rate of West Indian manatees (Trichechus manatus) during capture and handling in the field

West Indian manatees (Trichechus manatus) are captured, handled, and transported to facilitate conservation, research, and rehabilitation efforts. Monitoring manatee oral temperature (OT), heart rate (HR), and respiration rate (RR) during out-of-water handling can assist efforts to maintain animal well-being and improve medical response to evidence of declining health. To determine effects of capture on manatee vital signs, we monitored OT, HR, and RR continuously for a 50-min period in 38 healthy, awake, juvenile and adult Florida manatees (T. m. latirostris) and 48 similar Antillean manatees (T. m. manatus). We examined creatine kinase (CK), potassium (K+), serum amyloid A (SAA), and lactate values for each animal to assess possible systemic inflammation and muscular trauma. OT range was 29.5 to 36.2° C, HR range was 32 to 88 beats/min, and RR range was 0 to 17 breaths/5 min. Antillean manatees had higher initial OT, HR, and RR than Florida manatees (p < 0.001). As monitoring time progressed, mean differences between the subspecies were no longer significant. High RR over monitoring time was associated with high lactate concentration. Antillean manatees had higher overall lactate values ([mean ± SD] 20.6 ± 7.8 mmol/L) than Florida manatees (13.7 ± 6.7 mmol/L; p < 0.001). We recommend monitoring manatee OT, HR, and RR during capture and handling in the field or in a captive care setting.

Aquatic Mammals

Estimating incision healing rate for surgically implanted acoustic transmitters from recaptured fish

Background Intracoelomic implantation of electronic tags has become a common method in fishery research, but rarely are fish examined by scientists after release to understand the extent that surgical incisions have healed. Walleye ( Sander vitreus ) are a valuable, highly exploited fishery resource in the Laurentian Great Lakes. Here, fishery capture of walleye with internal acoustic transmitters combined with a high reward program provided multiple opportunities to examine photographs and quantify the status of surgical incisions. Walleye ( n = 926) from reef and river spawning populations in Lake Erie and Lake Huron were implanted with acoustic transmitters during spring spawning events from 2011 to 2016. Incisions were closed with polydioxanone monofilament using two to three interrupted sutures. Out of 276 recaptured fish, 60 incision sites were clearly visible in photographs, and these were scored by two independent readers for incision closure, inflammation, and the presence of sutures. Results While incision sites were completely closed by 61 days post-release (95% CI 44–94), sutures remained for up to 866 days. Sutures were expelled serially during a protracted period, and the probability of observing at least one suture in a recaptured fish declined below 50% after 673 days (95% CI 442–1016). Inflammation at the incision increased during the first 71 days and then declined monotonically, remaining detectable at low levels. Conclusion Our results emphasized that sutures remained in free-ranging fish past the time when they were beneficial for incision healing. Most dissolvable sutures have been designed for use in endotherms where the body temperature and internal milieu differ dramatically from the conditions experienced by fishes in temperate climates. Identification of new suture materials for fish that facilitate healing while absorbing or dissolving in a reasonable period (e.g., a few weeks to three months) in colder temperatures (e.g., <12 °C) would be beneficial to mitigate potential adverse impacts from inflammation at the incision.

Animal Biotelemetry

Neither microcystin, nor nodularin, nor cylindrospermopsin directly interact with human toll-like receptors

Various stressors including temperature, environmental chemicals, and toxins can have profound impacts on immunity to pathogens. Increased eutrophication near rivers and lakes coupled with climate change are predicted to lead to increased algal blooms. Currently, the effects of cyanobacterial toxins on disease resistance in mammals is a largely unexplored area of research. Recent studies have suggested that freshwater cyanotoxins can elicit immunomodulation through interaction with specific components of innate immunity, thus potentially altering disease susceptibility parameters for fish, wildlife, and human health owing to the conserved nature of the vertebrate immune system. In this study, we investigated the effects of three microcystin congeners (LR, LA, and RR), nodularin-R, and cylindrospermopsin for their ability to directly interact with nine different human Toll-like receptors (TLRs)—key pathogen recognition receptors for innate immunity. Toxin concentrations were verified by LC/MS/MS prior to use. Using an established HEK293-hTLR NF-κB reporter assay, we concluded that none of the tested toxins (29–90 nM final concentration) directly interacted with human TLRs in either an agonistic or antagonistic manner. These results suggest that earlier reports of cyanotoxin-induced NF-κB responses likely occur through different surface receptors to mediate inflammation.

Chemosphere

Coupling gene-based and classic veterinary diagnostics improves interpretation of health and immune function in the Agassiz’s desert tortoise (Gopherus agassizii)

The analysis of blood constituents is a widely used tool to aid in monitoring of animal health and disease. However, classic blood diagnostics (i.e. hematologic and plasma biochemical values) often do not provide sufficient information to determine the state of an animal’s health. Field studies on wild tortoises and other reptiles have had limited success in drawing significant inferences between blood diagnostics and physiological and immunological condition. However, recent research using gene transcription profiling in the threatened Mojave desert tortoise ( Gopherus agassizii ) has proved useful in identifying immune or physiologic responses and overall health. To improve our understanding of health and immune function in tortoises, we evaluated both standard blood diagnostic (body condition, hematologic, plasma biochemistry values, trace elements, plasma proteins, vitamin A levels) and gene transcription profiles in 21 adult tortoises (11 clinically abnormal; 10 clinically normal) from Clark County, NV, USA. Necropsy and histology evaluations from clinically abnormal tortoises revealed multiple physiological complications, with moderate to severe rhinitis or pneumonia being the primary cause of morbidity in all but one of the examined animals. Clinically abnormal tortoises had increased transcription for four genes (SOD, MyD88, CL and Lep), increased lymphocyte production, biochemical enzymes and organics, trace elements of copper, and decreased numbers of leukocytes. We found significant positive correlations between increased transcription for SOD and increased trace elements for copper, as well as genes MyD88 and Lep with increased inflammation and microbial insults. Improved methods for health assessments are an important element of monitoring tortoise population recovery and can support the development of more robust diagnostic measures for ill animals, or individuals directly impacted by disturbance.

Conservation Physiology