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Indian Journal of Nuclear Medicine :... 2015Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal chelating moiety in variety of conditions. In nuclear medicine itself two types of Tc-99m DMSA... (Review)
Review
Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal chelating moiety in variety of conditions. In nuclear medicine itself two types of Tc-99m DMSA complexes are used, trivalent and pentavalent forms. In this review, we have discussed the mechanism of uptake of both complexes as well as diagnostic and therapeutic application in a clinical scenario.
PubMed: 26430311
DOI: 10.4103/0972-3919.164015 -
Complementary Medicine Research 2017Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here,...
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy.
CASE REPORT
In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient's teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86 × 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely.
CONCLUSIONS
The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.
Topics: Amyotrophic Lateral Sclerosis; Dental Amalgam; Dental Restoration, Permanent; Environmental Exposure; Humans; Male; Mercury; Middle Aged; Muscular Atrophy, Spinal; Selenium; Thioctic Acid; Treatment Outcome; Unithiol
PubMed: 28641283
DOI: 10.1159/000477397 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jan 2024To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with pneumonia (MPP) and atelectasis and its effect on pulmonary... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with pneumonia (MPP) and atelectasis and its effect on pulmonary function.
METHODS
A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023. The children were randomly divided into a treatment group and a control group, with 47 children in each group. The children in the treatment group were given conventional treatment, BAL, and prone positioning, and those in the control group were given conventional treatment and BAL. The two groups were compared in terms of fever, pulmonary signs, length of hospital stay, lung recruitment, and improvement in pulmonary function.
RESULTS
Compared with the control group, the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization, on the day of discharge, and at 1 week after discharge (<0.05). Compared with the control group, the treatment group had significantly higher levels of forced vital capacity (FVC) as a percentage of the predicted value, forced expiratory volume (FEV) in 1 second as a percentage of the predicted value, ratio of FEV in 1 second to FVC, forced expiratory flow at 50% of FVC as a percentage of the predicted value, forced expiratory flow at 75% of FVC as a percentage of the predicted value, and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge (<0.05). There was no significant difference in the time for body temperature to return to normal between the two groups (>0.05).
CONCLUSIONS
In the treatment of children with MPP and atelectasis, BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.
Topics: Child; Humans; Prospective Studies; Mycoplasma pneumoniae; Prone Position; Pulmonary Atelectasis; Pneumonia, Mycoplasma; Bronchoalveolar Lavage; Dimercaprol
PubMed: 38269456
DOI: 10.7499/j.issn.1008-8830.2308013 -
Nature Communications Dec 2020Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable...
Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and financial snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using murine in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents murine lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings support the translation of combinations of repurposed small molecule-based toxin inhibitors as broad-spectrum therapeutics for snakebite.
Topics: Animals; Antivenins; Asia; Benzamidines; Central America; Dimercaprol; Disease Models, Animal; Drug Combinations; Drug Evaluation, Preclinical; Guanidines; Kaplan-Meier Estimate; Male; Mice; Neutralization Tests; Serine Proteases; Snake Bites; Toxins, Biological; Viper Venoms
PubMed: 33323937
DOI: 10.1038/s41467-020-19981-6 -
Basic & Clinical Pharmacology &... Jun 2017The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcome, and treatment recommendations vary....
The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcome, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital 2 months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 μg/L) exceeded the population level of 5 μg/L by more than 70 times. Dimercaptopropane sulphonate sodium (DMPS; 600 mg/day orally) was administered for 14 days. One year later, the patient presented with dyspnoea on exertion, fatigue, depression and impaired sleep. His chest X-ray showed multiple opacities (size up to 2.8 cm), and psychological testing revealed a selective cognitive deficit in the area of visual attentiveness, flexibility, source memory and impairment of the motor speed of the dominant upper extremity. Mercury blood level was 158 μg/L and mercury urine output was 1380 μg/24 hr. DMPS (800 mg/day orally) was administered for 40 days; the patient eliminated up to 18 mg Hg/day. His Hg blood level and Hg urine output belong to the highest among reported cases. In spite of the therapy, the patient's blood Hg, complaints and psychological tests showed no improvement. This case report confirms that DMPS does not effectively remove intravenous deposits of metallic Hg.
Topics: Adult; Chelation Therapy; Humans; Injections, Intravenous; Male; Mercury Poisoning; Suicide, Attempted; Unithiol
PubMed: 27911474
DOI: 10.1111/bcpt.12725 -
The Turkish Journal of Pediatrics 2019Çelebi-Tayfur A, Yaradılmış RM, Ulus F, Çaltık-Yılmaz A, Özayar E, Koşar B, Büyükkaragöz B, Horasanlı E. Bismuth intoxication resulting in acute kidney...
Çelebi-Tayfur A, Yaradılmış RM, Ulus F, Çaltık-Yılmaz A, Özayar E, Koşar B, Büyükkaragöz B, Horasanlı E. Bismuth intoxication resulting in acute kidney injury in a pregnant adolescent girl. Turk J Pediatr 2019; 61: 292-296. Bismuth intoxication is a rare cause of acute kidney injury (AKI) and is usually reversible by appropriate therapeutic measures. We present here a case of an adolescent pregnant girl who developed AKI due to an overdose of colloidal bismuth subcitrate (CBS, total amount of 6 g). She received parenteral chelating agent dimercaprol for 14 days. Continuous venovenous hemodiafiltration (CVVHD) with high-flux membrane was carried out in the first 3 days of chelating therapy and intermittent hemodialysis for 11 days, thereafter. The patient recovered clinically and was discharged after 21 days. She gave birth to a healthy term boy. At the last visit, the baby was 6 months old with normal growth and development as well as normal kidney functions. Neither deterioration in renal functions nor emergence of proteinuria was recorded in the patient during follow-up care after hospital discharge. In cases of AKI due to an overdose of CBS, treatment with dimercaprol combined with high flux hemodiafiltration and subsequently hemodialysis appears to be both useful and safe for bismuth elimination.
Topics: Acute Kidney Injury; Adolescent; Bismuth; Drug Overdose; Female; Hemodiafiltration; Humans; Pregnancy; Pregnancy Complications; Renal Dialysis
PubMed: 31951346
DOI: 10.24953/turkjped.2019.02.024 -
Journal of Advanced Pharmaceutical... 2015Acne vulgaris is a chronic inflammatory disease, and its treatment is challenging due to the multifactorial etiology and emergence of antibiotic-resistant...
Acne vulgaris is a chronic inflammatory disease, and its treatment is challenging due to the multifactorial etiology and emergence of antibiotic-resistant Propionibacterium acnes strains. This study was focused to reduce antibiotics usage and find an alternate therapeutic source for treating acne. Lipid extracts of six Chlorella species were tested for inhibition of lipase, reactive oxygen species (ROS) production, cytokine production using P. acnes (Microbial Type Culture Collection 1951). Lipase inhibitory assay was determined by dimercaprol Tributyrate - 5, 5'- dithiobis 2-nitrobenzoic acid method and ROS production assay was performed using nitro-blue tetrazolium test. The anti-inflammatory activity of algal lipid extracts was determined by in vitro screening method based on inhibition of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) produced by human peripheral blood mononuclear cells. Minimum inhibitory concentration (MIC) values of lipid extracts were determined by microdilution method, and the fatty acid methyl esters (FAME) were analyzed by gas chromatography-mass spectroscopy. Chlorella ellipsoidea has the highest lipase inhibitory activity with 61.73% inhibition, followed by Chlorella vulgaris (60.31%) and Chlorella protothecoides (58.9%). Lipid extracts from C. protothecoides and C. ellipsoidea has significantly reduced the ROS production by 61.27% and 58.34% respectively. Inhibition of pro-inflammatory cytokines TNF-α showed the inhibition ranging from 58.39% to 78.67%. C. vulgaris has exhibited the MICvalue of 10 μg/ml followed by C. ellipsoidea, C. protothecoides and Chlorella pyrenoidosa (20 μg/ml). FAME analysis detected 19 fatty acids of which 5 were saturated fatty acids, and 14 were unsaturated fatty acids ranging from C14 to C24. The results suggest that lipid extracts of Chlorella species has significant inhibitory activity on P. acnes by inhibiting lipase activity. Further, anti-inflammatory reaction caused by the pathogen could be reduced by the inhibiting the production of ROS and inflammatory mediators TNF-α and exposes new frontiers on the antiacne activities of Chlorella lipid extracts.
PubMed: 25709963
DOI: 10.4103/2231-4040.150364 -
Scientific Reports May 2016Local changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces...
Local changes in pH are known to significantly alter the state and activity of proteins and enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. membranes) would therefore constitute an important pillar towards a physical mechanism of biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physicochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification and propagate - in analogy to sound - at velocities controlled by the interface's compressibility. With transient local pH changes of 0.6 directly observed at the interface and velocities up to 1.4 m/s this represents hitherto the fastest protonic communication observed. Furthermore simultaneously propagating mechanical and electrical changes in the lipid interface are detected, exposing the thermodynamic nature of these pulses. Finally, these pulses are excitable only beyond a threshold for protonation, determined by the pKa of the lipid head groups. This protonation-transition plus the existence of an enzymatic pH-optimum offer a physical basis for intra- and intercellular signaling via sound waves at interfaces, where not molecular structure and mechano-enyzmatic couplings, but interface thermodynamics and thermodynamic transitions are the origin of the observations.
Topics: Acoustics; Hydrogen-Ion Concentration; Lipids; Protons; Signal Transduction; Static Electricity; Thermodynamics; Unilamellar Liposomes; Unithiol
PubMed: 27216038
DOI: 10.1038/srep22874 -
Frontiers in Pharmacology 2023Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left with life-long sequelae. Current antivenom therapies have...
Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left with life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration in a clinical setting. Next-generation snakebite therapies are being widely investigated with the aim to improve cost, efficacy, and safety. In recent years several small molecule drugs have shown considerable promise for snakebite indication, with oral bioavailability particularly promising for community delivery rapidly after a snakebite. However, only two such drugs have entered clinical development for snakebite. To offset the risk of attrition during clinical trials and to better explore the chemical space for small molecule venom toxin inhibitors, here we describe the first high throughput drug screen against snake venom metalloproteinases (SVMPs)-a pathogenic toxin family responsible for causing haemorrhage and coagulopathy. Following validation of a 384-well fluorescent enzymatic assay, we screened a repurposed drug library of 3,547 compounds against five geographically distinct and toxin variable snake venoms. Our drug screen resulted in the identification of 14 compounds with pan-species inhibitory activity. Following secondary potency testing, four SVMP inhibitors were identified with nanomolar ECs comparable to the previously identified matrix metalloproteinase inhibitor marimastat and superior to the metal chelator dimercaprol, doubling the current global portfolio of SVMP inhibitors. Following analysis of their chemical structure and ADME properties, two hit-to-lead compounds were identified. These clear starting points for the initiation of medicinal chemistry campaigns provide the basis for the first ever designer snakebite specific small molecules.
PubMed: 38273820
DOI: 10.3389/fphar.2023.1328950 -
Advances in Respiratory Medicine Dec 2023Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative...
Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce. To address this issue, we included consecutive HS-PTB patients with negative sputum samples who underwent BAL between 2017 and 2018. Chest X-rays (CXR) and CT scans were evaluated by a chest radiologist blind to the final diagnosis. Independent predictors for PTB were assessed by multivariate regression, using all positive PTB patients between 2017 and 2019 (by sputum or BAL) as a control group ( = 41). Overall, 42 HS-PTB patients were included (mean age 51 ± 9, 36% female). BAL was a viable diagnostic for PTB in three (7%) cases and for other clinically relevant pathogens in six (14%). Independent predictors for PTB were ≥2 sub-acute symptoms (adjusted OR 3.18, 95% CI 1.04-9.8), CXR upper-lobe consolidation (AOR 8.70, 95% CI 2.5-29), and centrilobular nodules in chest CT (AOR 3.96, 95% CI 1.20-13.0, = 0.02). In conclusion, bronchoscopy with BAL in hospitalized patients with HS-PTB had a 7% added diagnostic value after negative sputum samples. Our findings highlight specific predictors for PTB diagnosis that could be used in future controlled studies to personalize the diagnostic evaluation.
Topics: Humans; Female; Adult; Middle Aged; Male; Mycobacterium tuberculosis; Sputum; Bronchoalveolar Lavage Fluid; Sensitivity and Specificity; Tuberculosis, Pulmonary; Bronchoalveolar Lavage; Dimercaprol
PubMed: 38392033
DOI: 10.3390/arm92010003