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Biomedicine & Pharmacotherapy =... Jan 2024Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases,... (Review)
Review
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
Topics: Animals; Male; Venoms; Sperm Motility; Peptides; Angiotensin II
PubMed: 38113629
DOI: 10.1016/j.biopha.2023.116015 -
Revista de Neurologia Nov 2020Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low...
INTRODUCTION
Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low levels of potassium in blood. As a consequence of its low prevalence, there are still clinical and management aspects to characterize.
PATIENTS AND METHODS
A systematic review of the clinical cases published in the last decade has been developed by analyzing demographic and genetic features, the episodes' characteristics, the received treatments, the response to them and also, the differences and evolution of patients depending on the most prevalent genetic alterations: CACNA1S and SCN4A.
RESULTS
A total of 33 articles were included, allowing 40 individuals to be reviewed. The average age of onset of symptoms was 15.3 ± 9.7 years. The most frequent altered gene was CACNA1S in 20 (60.5%) cases. It was observed that subjects presenting an alteration of the gene responsible for the calcium channel, CACNA1S, presented lower serum potassium levels, own triggers and a higher proportion of subjects showing dyspnea during the crisis. Only 50% of the subjects respond to classical oral treatment with acetazolamide. Potassium-sparing diuretics and antiepileptics drugs emerge as an alternative.
CONCLUSION
Hypokalemic periodic paralysis has an heterogeneous clinical expression with phenotypic differences linked to different genetic mutations. The common preventive treatment response is suboptimal. Prospective studies are needed to discern the best therapeutic option based on genetic load.
Topics: Acetazolamide; Age of Onset; Calcium Channels, L-Type; Gene Frequency; Humans; Hypokalemic Periodic Paralysis; NAV1.4 Voltage-Gated Sodium Channel; Potassium
PubMed: 33085076
DOI: 10.33588/rn.7109.2020377 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
The Cochrane Database of Systematic... 2003Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic disorder of neuromuscular transmission. Treatments have attempted to overcome the harmful autoimmune... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic disorder of neuromuscular transmission. Treatments have attempted to overcome the harmful autoimmune process, or to improve residual neuromuscular transmission, in order to reverse the principal neurological symptom of muscle weakness.
OBJECTIVES
The objective was to examine the efficacy of all forms of treatment in Lambert-Eaton myasthenic syndrome.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group specialised trials register (September 2002), MEDLINE (January 1966 to November 2002) and EMBASE (January 1980 to November 2002). We checked the bibliographies in reports of the randomised trials and contacted authors to identify additional published or unpublished data.
SELECTION CRITERIA
Types of studies: all randomised or quasi-randomised trials.
TYPES OF PARTICIPANTS
all adults and children with a diagnosis of Lambert-Eaton myasthenic syndrome, with or without small-cell lung cancer. Types of interventions: any form of medical (pharmacological or physical) treatment. Types of outcome measures: Primary: change in the muscle strength scale score (Quantitative Myasthenia Gravis score), or limb muscle strength measured by myometry. Secondary: improvement in the mean amplitude of the resting compound muscle action potentials. The mean amplitude used was the mean of all muscles tested.
DATA COLLECTION AND ANALYSIS
We identified three randomised controlled trials. Individual patient data were only available for one trial.
MAIN RESULTS
The three eligible trials included two controlled trials of the effects of 3,4-diaminopyridine compared with placebo in a total of 38 patients with Lambert-Eaton myasthenic syndrome, one of which was of crossover design. A third crossover trial compared intravenous immunoglobulin treatment to placebo in nine patients with Lambert-Eaton myasthenic syndrome. A meta-analysis of the primary endpoint results of these trials was not possible because of differences in comparisons and endpoints and, in two trials, lack of individual patient data. EFFECTS OF 3,4-DIAMINOPYRIDINE: Two trials of 3,4-diaminopyridine reported a significant improvement in the primary endpoint of muscle strength score, or myometric limb measurement following treatment. Both trials also reported a significant improvement in the secondary endpoint of resting compound muscle action potential amplitude following 3,4-diaminopyridine, compared with placebo. A meta-analysis of the primary endpoint results was not possible because of marked differences in these two trials regarding primary outcome measures. However, a meta-analysis of the secondary endpoint (improvement in the amplitude of the mean resting compound muscle action potential) was possible. It was necessary to assume a known correlation (similarity) of the paired responses for each individual in the two treatment periods in order to properly allow for the crossover design of one of the two trials (the correlation coefficient was assumed to be 0.5 in calculations). Using this approach, meta-analysis revealed a significant overall benefit in compound muscle action potential amplitude after 3,4-diaminopyridine treatment. The overall weighted mean difference was 1.80 mV (95% confidence interval 0.82 to 2.78), favouring treatment. These results were not sensitive to the assumption made because the overall benefit estimated was still significant when the correlation was assumed to be less than 0.1. EFFECTS OF INTRAVENOUS IMMUNOGLOBULIN: A crossover trial reported a significant improvement in the primary outcome measure of myometric limb strength when patients received intravenous immunoglobulin compared to placebo infusions. This trial also demonstrated an improvement in the secondary outcome measure of change in the mean resting compound muscle action potential amplitude following intravenous immunoglobulin, but this improvement did not reach significance. Clinical improvement lasted for up to eight weeks.
REVIEWER'S CONCLUSIONS
Limited evidence from randomised controlled trials showed that either 3,4-diaminopyridine or intravenous immunoglobulin improved muscle strength scores and compound muscle action potential amplitudes in patients with Lambert-Eaton myasthenic syndrome. There are insufficient data at present to quantify this treatment effect. Other possible treatments, such as plasma exchange, steroids and immunosuppressive agents have not been tested in randomised controlled trials.
Topics: 4-Aminopyridine; Amifampridine; Humans; Immunoglobulins, Intravenous; Lambert-Eaton Myasthenic Syndrome; Potassium Channel Blockers; Randomized Controlled Trials as Topic
PubMed: 12804456
DOI: 10.1002/14651858.CD003279 -
Systems Biology in Reproductive Medicine Aug 2021Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered...
Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered methylation of sperm-imprinted genes associates with sperm DNA fragmentation (SDF), pregnancy loss rate and assisted reproductive technique (ART) outcome. To accomplish this, Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases were used for search strategy from each database inception until December 2020. Specific keywords were used. Studies satisfying the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model were retrieved. Ten studies could be included in the qualitative analysis. A significant association was reported between increased SDF rate and aberrant methylation of / and genes by two studies. A significantly lower methylation was found in patients with idiopathic recurrent pregnancy loss (RPL) and in infertile patients compared to fertile men. Methylation of /, and / were similar in patients with RPL and controls. The ART outcome was similar in patients with aberrant and normal methylation of /, and . By contrast, a study showed an association between altered GLT2 methylation and more inferior ART results. If further confirmed by well-sized studies, these data might be helpful to identify possible epigenetic predictors of ART outcome. Particularly, aberrant methylation of and genes might represent interesting targets that deserve further investigation.
Topics: Abortion, Habitual; DNA Methylation; Female; Genomic Imprinting; Humans; KCNQ1 Potassium Channel; Male; Pregnancy; RNA, Long Noncoding; Reproductive Techniques, Assisted; Spermatozoa
PubMed: 34080930
DOI: 10.1080/19396368.2021.1909667 -
Cephalalgia : An International Journal... Feb 2018Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2... (Meta-Analysis)
Meta-Analysis
Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.
Topics: Epilepsy; Humans; Migraine with Aura; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Sodium-Potassium-Exchanging ATPase
PubMed: 28058944
DOI: 10.1177/0333102416686347 -
Atencion Primaria Nov 2000To describe the benefits of treatment for hypertension in the elderly, the most efficient drugs, those most widely used in clinical practice to reduce morbi-mortality... (Review)
Review
OBJECTIVES
To describe the benefits of treatment for hypertension in the elderly, the most efficient drugs, those most widely used in clinical practice to reduce morbi-mortality taken from the literature.
DESIGN
Systematic review.
PARTICIPANTS
Review study in Medline and the Cochrane Collaboration database. The antihypertensive pharmacological treatment is described (diuretics high and low dosage, calcium channel blockers, ACE inhibitor, and beta-blockers) administered to elderly people and their outcomes in morbi-mortality.
MEASUREMENTS AND MAIN RESULTS
Reduction in coronary and cerebral morbidity and general, cardiovascular and cerebrovascular mortality.
RESULTS
There is evidence to suggest that treatment for hypertension is helpful in the elderly, although efficiency is doubtful in patients over 80 years old. For persons aged over 65 general mortality is RR = 0.84 (0.75-0.94) and coronary morbidity RR = 0.80 (0.70-0.92). For persons aged over 80 general mortality is RR = 1 (0.86-1.17) and cardiovascular mortality is RR = 0.94 (0.75-1.18). Not all pharmacological groups produce the same results in mortality and morbidity. Diuretics (low dosage) offer better results than the remaining treatments reducing cardiovascular mortality as well cerebrovascular morbidity.
CONCLUSIONS
Treatment with drugs in hypertense elderly people is beneficial in terms of mortality and morbidity. Treatment with low dose diuretics, with or without potassium savers, is the elective treatment for hypertension in elderly patients.
Topics: Aged; Antihypertensive Agents; Clinical Trials as Topic; Humans; Hypertension; Treatment Outcome
PubMed: 11149186
DOI: 10.1016/s0212-6567(00)78718-x -
Medicine Jun 2019Studies showed the controversial results about the effect of common genetic polymorphisms on the atrial fibrillation (AF) recurrence. We performed the systematic review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies showed the controversial results about the effect of common genetic polymorphisms on the atrial fibrillation (AF) recurrence. We performed the systematic review and meta-analysis to qualify the association between common genetic polymorphisms and AF recurrence.
METHODS
Articles were systematically retrieved PubMed, Web of Science, EMBASE, Wanfang, and CNKI database and 9 studies including 3204 patients were enrolled in our meta-analysis.
RESULTS
Results showed that the associations were significant under rs2200733 3 genetic models (TT vs CC: odds ratio [OR] [confidence interval [CI]] = 1.336 [1.061-1.683], P = .014; CT vs CC: OR [CI] = 0.759 [0.614-0.937], P = .01; TT vs CT + CC: OR [CI] = 2.308 [1.440-3.700], P = .001). The association was significant under rs10033464 genetic model (TT vs GG: OR [CI] = 1.517 [1.165-1.976], P = .002).
CONCLUSIONS
Rs13376333 on chromosome 1q21 (in KCNN3), rs7193343 and rs2106261 on chromosome 16q22 (in ZFHX3) were not associated with AF recurrence in our meta-analysis. In total, our meta-analysis found that rs2200733 and rs10033464 on chromosome 4q25 (near PITX2) were associated with the risk of AF recurrence.
Topics: Aged; Atrial Fibrillation; Chromosomes, Human; Female; Genetic Predisposition to Disease; Homeodomain Proteins; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Recurrence; Small-Conductance Calcium-Activated Potassium Channels; Transcription Factors; Homeobox Protein PITX2
PubMed: 31169720
DOI: 10.1097/MD.0000000000015953 -
Diabetes/metabolism Research and Reviews Nov 2021More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55... (Review)
Review
More than 1000 variants of the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene have been reported in neonatal diabetes mellitus. Up to now only 55 ABCC8 variants were associated with Maturity-Onset Diabetes of the Young 12 (MODY12). We present a c.3544C>T p.(Arg1182Trp) ABCC8 variant in a 35-year-old women who had pronounced microvascular diabetic complications and a charcot arthropathy necessitating a lower limb amputation. The unusual severity of the disease course prompted us to perform a systematic review of all genetic variants in MODY12. The present mutation has mostly been associated with neonatal diabetes and in only three papers reporting a MODY12. The 55 MODY12 variants show a large clinical heterogeneity, even in relatives with the same mutation, ranging from mild impaired glucose tolerance to severe insulin-dependent diabetes mellitus. HbA1c at diagnosis ranged from 5% to 14% and age at diagnosis ranged from 2 to 53 years. However, several case reports lack documentation of diabetic complications. Hence, more detailed reports remain necessary to improve insight in MODY12 pathophysiology and outcome. In this article current data regarding therapeutic management are provided, and key points to consider for the individual patient affected by MODY12 are presented.
Topics: Adult; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Infant, Newborn; Middle Aged; Mutation; Sulfonylurea Receptors
PubMed: 34014594
DOI: 10.1002/dmrr.3459 -
Antiviral Therapy 2019The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV (PLWH).
METHODS
A systematic literature search using PubMed and Google Scholar databases was performed using the following search terms: 'HIV and prolonged QTc' and 'managing HIV-patients with prolonged QTc'. References within articles of interest were also evaluated.
RESULTS/DISCUSSION
PLWH are at an increased risk of having a prolonged QTc interval. Some risk factors for this include the virus itself, concomitant medications, comorbid conditions, addictions and electrolyte disturbances. PLWH who have an increased HIV RNA viral load or decreased CD4 T-cell count are at further risk for progressing to sudden cardiac death (SCD). Many medications commonly prescribed in the PLWH population, such as antiretrovirals and antimicrobials used in opportunistic infection prophylaxis, have also been shown to promote QTc prolongation through inhibition of human ether-a-go-go potassium channels or through drug metabolism inhibition of other QTc prolonging drugs.
CONCLUSIONS
Due to the high number of risk factors associated with QTc prolongation, clinicians should incorporate baseline and routine ECG monitoring for PLWH to potentially lower the increased risk of SCD in PLWH.
Topics: Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Death, Sudden, Cardiac; Disease Management; Female; HIV Infections; Humans; Long QT Syndrome; Male; Prevalence; Risk Assessment; Risk Factors; Viral Load
PubMed: 31570667
DOI: 10.3851/IMP3335