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Viruses Jun 2022Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they... (Review)
Review
Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was followed by wide skepticism when in vivo assays refuted the initial results. In this paper we review the use of sulfated polysaccharides, and other polyanions, in antiviral therapy, focusing on extracellular polymeric substances (EPSs). We maintain that, in spite of those early difficulties, the use of polyanions and, specifically, the use of EPSs, in antiviral therapy should be reconsidered. We base our claim in several points. First, early studies showed that the main disadvantage of sulfated polysaccharides and polyanions is their low bioavailability, but this difficulty can be overcome by the use of adequate administration strategies, such as nebulization of aerosols to gain access to respiratory airways. Second, several sulfated polysaccharides and EPSs have demonstrated to be non-toxic in animals. Finally, these macromolecules are non-specific and therefore they might be used against different variants or even different viruses.
Topics: Animals; Antiviral Agents; Extracellular Polymeric Substance Matrix; HIV Infections; Polysaccharides
PubMed: 35746808
DOI: 10.3390/v14061337 -
Clinical Psychopharmacology and... Feb 2021Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of... (Review)
Review
Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of different levels of the neuraxis. Several psychotropic drug classes and combinations have been associated with a classic clinical syndrome of hyperthermia, skeletal muscle hyper-metabolism, rigidity or rhabdomyolysis, autonomic dysfunction and altered mental status ranging from catatonic stupor to coma. It is critical for clinicians to have a high index of suspicion for these relatively uncommon drug-induced adverse effects and to become familiar with their management to prevent serious morbidity and mortality. Although these syndromes look alike, they are triggered by quite different mechanisms, and apart from the need to withdraw or restore potential triggering drugs and provide intensive medical care, specific treatments may vary. Clinical similarities have led to theoretical speculations about common mechanisms and shared genetic predispositions underlying these syndromes, suggesting that there may be a common "thermic stress syndrome" triggered in humans and animal models by a variety of pharmacological or environmental challenges.
PubMed: 33508784
DOI: 10.9758/cpn.2021.19.1.1 -
International Journal of Molecular... Jan 2022Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous... (Review)
Review
Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.
Topics: Animals; Drug Administration Routes; Drug Compounding; Humans; Models, Animal; Neuropeptides; Organ Specificity; Regeneration; Substance P; Wound Healing
PubMed: 35054936
DOI: 10.3390/ijms23020750 -
Cureus Feb 2022Hospitals, clinics, and organizations using controlled substances must have policies and procedures in place for disposing of these substances and to avoid potential... (Review)
Review
Hospitals, clinics, and organizations using controlled substances must have policies and procedures in place for disposing of these substances and to avoid potential drug diversion as well as environmental pollution. Challenging, particularly to hospitals, is the ability to dispose of the waste of any number of hundreds of products every day, some of which require specific handling and protocols for safety. Incineration might be appropriate but many hospitals and certainly smaller clinics lack the appropriate facilities. Clinics and facilities that use controlled substances must maintain adequate and detailed records, but individual healthcare systems impose their own specific requirements. Some, for example, require drug disposal to be witnessed. However, recordkeeping systems must be robust and frequently audited to prevent diversion. Most healthcare systems want to dispose of controlled substances in an environmentally responsible way but in addition to federal laws in the United States, most states have their own environmental agencies and may have local regulations. Navigating this system can be complex, and since all regulations are subject to change, it requires vigilance and expertise.
PubMed: 35371798
DOI: 10.7759/cureus.22564 -
Toxics Sep 2023Abusing controlled substances, including cannabis and various drugs, can result in severe intoxication and even death. Therefore, a comprehensive postmortem analysis is... (Review)
Review
Abusing controlled substances, including cannabis and various drugs, can result in severe intoxication and even death. Therefore, a comprehensive postmortem analysis is crucial for understanding the underlying causes of such fatalities. This narrative review discusses the characteristics of commonly abused controlled substances, the methodologies employed in postmortem analysis, lethal dosage levels, mechanisms of toxicity, side effects, and existing regulations. The focus centers on seven prevalent groups of controlled substances, namely cannabis, opioids, amphetamine-type stimulants, cocaine, new psychoactive substances, and hallucinogens. These groups have been linked to an increased risk of fatal overdose. Most substances in these groups exert neurotoxic effects by targeting the central nervous system (CNS). Consequently, strict regulation is essential to mitigate the potential harm posed by these substances. To combat abuse, prescribers must adhere to guidelines to ensure their prescribed medications comply with the outlined regulations. Through an enhanced understanding of controlled substance abuse and its consequences, more effective strategies can be developed to reduce its prevalence and associated mortality.
PubMed: 37755766
DOI: 10.3390/toxics11090756 -
The Western Journal of Emergency... Jul 2020Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in... (Review)
Review
INTRODUCTION
Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in aggressive acts has better informed our interventions through pharmacologic and behavioral strategies. This paper reviews the literature on the neurobiological underpinnings of aggressive behaviors, linking psychopathology with proposed mechanisms of action of psychiatric medications shown to be effective in mitigating agitation.
METHODS
We performed a review of the extant literature using PubMed as a primary database. Investigation focused on neurobiology of agitation and its relation to the current evidence base for particular interventions.
RESULTS
There are well-established pathways that can lead to increased autonomic response and the potential for violence. Psychopathology and substance-induced perceptual distortions may lead to magnification and overestimation of environmental threat, heightening the potential for aggression. Additional challenges have arisen with the advent of several novel drugs of abuse, many of which lead to atypical clinical presentations and which can elude standard drug screens. Our interventions still lean on the evidence base found in Project BETA (Best Practices in Evaluation and Treatment of Agitation). Although not a new drug and not included in the Project BETA guidelines, ketamine and its use are also discussed, given its unique pharmacology and potential benefits when other protocoled interventions have failed.
CONCLUSION
Aggression can occur due to manifold reasons in the clinical setting. Having an informed understanding of the possible determinants of agitation can help with more tailored responses to individual patients, limiting the unnecessary use of medications or of interventions that could be deemed forceful.
Topics: Aggression; Humans; Psychomotor Agitation; Psychotropic Drugs
PubMed: 32726254
DOI: 10.5811/westjem.2020.4.45779 -
Biomolecules Jan 2021Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester... (Review)
Review
Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester (CAPE), is one of the most extensively investigated active components of propolis. Several studies have indicated that CAPE has a broad spectrum of pharmacological activities as anti-oxidant, anti-inflammatory, anti-viral, anti-fungal, anti-proliferative, and anti-neoplastic properties. This review largely describes CAPE neuroprotective effects in many different conditions and summarizes its molecular mechanisms of action. CAPE was found to have a neuroprotective effect on different neurodegenerative disorders. At the basis of these effects, CAPE has the ability to protect neurons from several underlying causes of various human neurologic diseases, such as oxidative stress, apoptosis dysregulation, and brain inflammation. CAPE can also protect the nervous system from some diseases which negatively affect it, such as diabetes, septic shock, and hepatic encephalopathy, while numerous studies have demonstrated the neuroprotective effects of CAPE against adverse reactions induced by different neurotoxic substances. The potential role of CAPE in protecting the central nervous system (CNS) from secondary injury following various CNS ischemic conditions and CAPE anti-cancer activity in CNS is also reviewed. The structure-activity relationship of CAPE synthetic derivatives is discussed as well.
Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents; Antifungal Agents; Antioxidants; Antiviral Agents; Apoptosis; Brain; Caffeic Acids; Humans; Inflammation; Ischemia; Neurodegenerative Diseases; Parkinson Disease; Phenylethyl Alcohol; Propolis; Psychotic Disorders; Seizures
PubMed: 33525407
DOI: 10.3390/biom11020176 -
Molecules (Basel, Switzerland) Nov 2019Dinucleoside 5',5'-polyphosphates (DNPs) are endogenous substances that play important intra- and extracellular roles in various biological processes, such as cell... (Review)
Review
Dinucleoside 5',5'-polyphosphates (DNPs) are endogenous substances that play important intra- and extracellular roles in various biological processes, such as cell proliferation, regulation of enzymes, neurotransmission, platelet disaggregation and modulation of vascular tone. Various methodologies have been developed over the past fifty years to access these compounds, involving enzymatic processes or chemical procedures based either on P(III) or P(V) chemistry. Both solution-phase and solid-support strategies have been developed and are reported here. Recently, green chemistry approaches have emerged, offering attracting alternatives. This review outlines the main synthetic pathways for the preparation of dinucleoside 5',5'-polyphosphates, focusing on pharmacologically relevant compounds, and highlighting recent advances.
Topics: Deoxycytosine Nucleotides; Dinucleoside Phosphates; Dry Eye Syndromes; Green Chemistry Technology; Humans; Ophthalmic Solutions; Phosphorylation; Polyphosphates; Purinergic P2Y Receptor Agonists; Receptors, Purinergic; Uracil Nucleotides; Uridine
PubMed: 31783537
DOI: 10.3390/molecules24234334 -
Naunyn-Schmiedeberg's Archives of... May 2024Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or... (Review)
Review
Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or violent and criminal circumstances. Examples for the first scenario is the release of toxic gases, chemicals, and particles during house fires, and for the second scenario, the use of chemical or biological weapons in the context of terroristic activities. Toxic substances can cause or enhance severe, life-threatening trauma, as described in this review for various chemical warfare, by inducing a tissue trauma accompanied by break down of important barriers in the body, such as the blood-air or the blood-gut barriers. This in turn initiates a "vicious circle" as the contribution of inflammatory responses to the traumatic damage enhances the macro- and micro-barrier breakdown and often results in fatal outcome. The development of sophisticated methods for detection and identification of toxic substances as well as the special treatment of the intoxicated trauma patient is summarized in this review. Moreover, some highly toxic substances, such as the protein toxins from the pathogenic bacterium Clostridioides (C.) difficile, cause severe post-traumatic complications which significantly worsens the outcome of hospitalized patients, in particular in multiply injured trauma patients. Therefore, novel pharmacological options for the treatment of such patients are necessarily needed and one promising strategy might be the neutralization of the toxins that cause the disease. This review summarizes recent findings on the molecular and cellular mechanisms of toxic chemicals and bacterial toxins that contribute to barrier breakdown in the human body as wells pharmacological options for treatment, in particular in the context of intoxicated trauma patients. "trauma-toxicology" comprises concepts regrading basic research, development of novel pharmacological/therapeutic options and clinical aspects in the complex interplay and "vicious circle" of severe tissue trauma, barrier breakdown, pathogen and toxin exposure, tissue damage, and subsequent clinical complications.
Topics: Humans; Animals; Wounds and Injuries
PubMed: 37999755
DOI: 10.1007/s00210-023-02845-3 -
Journal of Personalized Medicine Aug 2020The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under... (Review)
Review
The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at <10 kDa; Imuno TF), anti-inflammatory natural blend (, and Miodesin), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms.
PubMed: 32764275
DOI: 10.3390/jpm10030080