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Genes Jan 2024Despite being a non-hematophagous leech, is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high...
Despite being a non-hematophagous leech, is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high quality genome of and based on which, we performed a systematic identification of the potential antithrombotic genes and their corresponding proteins. We identified twenty antithrombotic gene families including thirteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. Unexpectedly, a total of 79 antithrombotic genes were identified, more than a typical blood-feeding , which had only 72 antithrombotic genes. In addition, combining with the RNA-seq data of and , we calculated the expression levels of antithrombotic genes of the two species. Five and four gene families had significantly higher and lower expression levels in than in , respectively. These results showed that the number and expression level of antithrombotic genes of a non-hematophagous leech are not always less than those of a hematophagous leech. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a non-hematophagous leech to date and will significantly enhance the investigation and utilization of leech derivatives in thrombosis therapy research and pharmaceutical applications.
Topics: Animals; Humans; Fibrinolytic Agents; Leeches; Thrombosis; Platelet Aggregation Inhibitors; Chromosomes
PubMed: 38397154
DOI: 10.3390/genes15020164 -
Journal of Vector Borne Diseases Feb 2024Amphotericin B, Allopurinol, Glucantime and Beta-Glucan are the main drugs currently used for the treatment of cutaneous leishmaniasis. In present study, we evaluated...
BACKGROUND OBJECTIVES
Amphotericin B, Allopurinol, Glucantime and Beta-Glucan are the main drugs currently used for the treatment of cutaneous leishmaniasis. In present study, we evaluated the effect of medical leeches on BALB/c mice models infected with Leishmania parasites.
METHODS
To create animal models of leishmaniasis, BALB/c mice were inoculated with the standard Leishmania major strain MRHO / IR / 75 / ER. Treatment was performed through blood sampling with leeches. We used medical leech (Hirudo medicinalis) species. This leech is a European medicinal leech, one of several species known used as medicinal leech. 22 mice infected with Leishmania major were used for the tests .The studied mice were divided into two groups which were named with the letters L and D. The duration of blood sampling was 25 min for initial treatment, 20 min for the 2nd blood sampling and 15 min for the third times and onwards. Meglumine antimoniate (Glucantime) is a pentavalent antimony (SbV) that recommended by the World Health Organization as a golden standard treatment for all kind of leishmaniasis, but many side effects are still reported. Criteria for anti-leshmania assessment of Leech were including: Leech saliva has an anti-leishmania effect by acting on the purin pathway. Leech saliva prevents the growth and multiplication of Leishmania by a mechanism of action similar to Glucantim (breaking ATP).
RESULTS
The duration of leech treatment in BALB/c mice infected with L.major parasites was about 6-8 weeks. Out of the 22 leishmaniasis mice models that underwent treatment, 13 survived until the end of the treatment duration. The recovery rate was about 56%; lesions improved in five out of the 13 surviving mice models. Paired t-test showed a significant difference between the mean wound size at the beginning of treatment and the 8th week of treatment (PV <0.0001).
INTERPRETATION CONCLUSION
Considering the fact that the standard drugs for the treatment of leishmaniasis have many side effects, alternative therapies such as leech therapy can be effectively used to treat these chronic wounds. There are about 20 active substances in leech saliva. These substances include antistasin, eglins, guamerin, hirudin, saratin, bdellins, complement, and carboxypeptidase inhibitors. Leech saliva is an anticoagulant, anti-inflammation and prevents the platelet. Leech therapy was effective in treating leishmaniasis wounds in BALB/c mice. In this study, there was complete wound healing in 56% of the mice models.
PubMed: 38358005
DOI: 10.4103/JVBD.JVBD_114_22 -
Frontiers in Endocrinology 2024Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective... (Review)
Review
Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.
Topics: Animals; Humans; Diabetic Nephropathies; Hirudins; Kidney; Medicine, Chinese Traditional; Leeches; Diabetes Mellitus
PubMed: 38344666
DOI: 10.3389/fendo.2024.1296843 -
Therapeutic Advances in Cardiovascular... 2024Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels... (Review)
Review
Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.
Topics: Humans; Angina Pectoris, Variant; Coronary Vasospasm; Quality of Life; Coronary Angiography; Coronary Artery Disease; Myocardial Infarction; Chest Pain; Spasm
PubMed: 38343041
DOI: 10.1177/17539447241230400 -
World Journal of Plastic Surgery 2023This study aims to explain microscopic replantation in a rare case of a wholly amputated penis after prolonged ischemia. A 36-year-old patient underwent microscopic...
This study aims to explain microscopic replantation in a rare case of a wholly amputated penis after prolonged ischemia. A 36-year-old patient underwent microscopic replantation of the penis after 9 hours. The penis was completely amputated due to self-mutilation. Microvascular replantation was performed after pre-operative preparation. On the second day after surgery, congestion was observed in the penis, and three sessions of leech therapy were conducted each time the leeches were placed for 30 minutes and then detached by themselves. The patient was referred to a psychiatrist to continue treatment after discharge from the hospital. Penile amputation is a rare situation and has different causes. There are various treatments to repair the amputated penis, which are both microvascular and microvascular. The microsurgery methods have shown the best results. In the present case, due to microsurgical artery repair and the early start of leech therapy, there was limited and predictable necrosis in the area of the penoscrotal junction flap, which underwent debridement and skin graft. Complete amputation of the penis is a rare phenomenon. Efforts should be made to perform the replantation surgery as soon as possible. The venous outflow is an essential factor in the success of penile re-implantation, and completely restored vascular and sensory function in this case. Early initiation of psychological care to control underlying disease leads to further cooperation of the patient to handle complications and avoid the recurrence of self-injury.
PubMed: 38226201
DOI: 10.61186/wjps.12.3.18 -
BMC Medicine Dec 2023Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic...
BACKGROUND
Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations.
METHODS
Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national).
RESULTS
Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001).
CONCLUSIONS
Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials.
TRIAL REGISTRATION
NCT01581476. Registered on 20 April 2012.
Topics: Adolescent; Humans; Australia; Canada; Clinical Trials as Topic; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Retrospective Studies; Socioeconomic Factors
PubMed: 38124088
DOI: 10.1186/s12916-023-03222-w -
Journal of Research in Medical Sciences... 2023
PubMed: 38024521
DOI: 10.4103/jrms.jrms_199_22 -
Protein Science : a Publication of the... Dec 2023Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy...
From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).
Hirudin from Hirudo medicinalis is a bivalent α-Thrombin (αT) inhibitor, targeting the enzyme active site and exosite-I, and is currently used in anticoagulant therapy along with its simplified analogue hirulog. Haemadin, a small protein (57 amino acids) isolated from the land-living leech Haemadipsa sylvestris, selectively inhibits αT with a potency identical to that of recombinant hirudin (K = 0.2 pM), with which it shares a common disulfide topology and overall fold. At variance with hirudin, haemadin targets exosite-II and therefore (besides the free protease) it also blocks thrombomodulin-bound αT without inhibiting the active intermediate meizothrombin, thus offering potential advantages over hirudin. Here, we produced in reasonably high yields and pharmaceutical purity (>98%) wild-type haemadin and the oxidation resistant Met5 → nor-Leucine analogue, both inhibiting αT with a K of 0.2 pM. Thereafter, we used site-directed mutagenesis, spectroscopic, ligand-displacement, and Hydrogen/Deuterium Exchange-Mass Spectrometry techniques to map the αT regions relevant for the interaction with full-length haemadin and with the synthetic N- and C-terminal peptides Haem(1-10) and Haem(45-57). Haem(1-10) competitively binds to/inhibits αT active site (K = 1.9 μM) and its potency was enhanced by 10-fold after Phe3 → β-Naphthylalanine exchange. Conversely to full-length haemadin, haem(45-57) displays intrinsic affinity for exosite-I (K = 1.6 μM). Hence, we synthesized a peptide in which the sequences 1-9 and 45-57 were joined together through a 3-Glycine spacer to yield haemanorm, a highly potent (K = 0.8 nM) inhibitor targeting αT active site and exosite-I. Haemanorm can be regarded as a novel class of hirulog-like αT inhibitors with potential pharmacological applications.
Topics: Hirudins; Thrombin; Amino Acid Sequence; Peptides; Heme
PubMed: 37924304
DOI: 10.1002/pro.4825 -
JAMA Nov 2023Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute...
IMPORTANCE
Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.
OBJECTIVE
To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.
DESIGN, SETTING, AND PARTICIPANTS
CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.
INTERVENTION
Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 28 days in the intention-to-treat population.
RESULTS
Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).
CONCLUSIONS AND RELEVANCE
Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.
Topics: Adult; Male; Humans; Middle Aged; Female; Hemorrhage; Fibrinogen; Blood Transfusion; Blood Component Transfusion; Wounds, Penetrating
PubMed: 37824155
DOI: 10.1001/jama.2023.21019 -
Cureus Sep 2023Medicinal leech therapy (MLT) is used in various medical disciplines, among which are reconstructive surgery and microsurgery. Medicinal leech therapy is also often...
Medicinal leech therapy (MLT) is used in various medical disciplines, among which are reconstructive surgery and microsurgery. Medicinal leech therapy is also often adopted by alternative and traditional medicine, aiming to treat various common medical symptoms, such as fever and arthritis. Congenital umbilical hernia is a rather common physical finding in the pediatric population, where every third Caucasian newborn, roughly, is being diagnosed with the condition, and even more so among the African population. Fortunately, most cases resolve spontaneously in the first years of life. Toddlers whose hernia does not close typically require umbilical hernia repair. This article describes the case of a five-year-old girl with an asymptomatic congenital umbilical hernia who was admitted to the ER due to an omental eventration that occurred following the placement of a leech on her umbilicus in her parents' attempt to treat a febrile episode. She subsequently underwent an urgent umbilical exploration and a repair of her umbilical hernia. The main known risks of leeching are bacterial infection, anemia, prolonged bleeding, and, less frequently, pruritus, allergies, marked edema, and cellulitis. This article presents yet another possible complication that, to the best of our knowledge, has not been documented before in the literature. Several old-school therapies transcended over time into medical disciplines. Given that "traditional" practices often take place within households and communities, it is of crucial importance to point out potential complications, both rare and common, that can be caused by those practices in order to reduce the risk of severe, undesired outcomes. Indeed, the growing interface between traditional, alternative therapies and modern, conventional medicine urges better parental guidance and improved education regarding potentially harmful and unauthorized interventions.
PubMed: 37809215
DOI: 10.7759/cureus.44831