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BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is a consequential dermal manifestation of visceral leishmaniasis (VL), serving as a parasite reservoir. The traditional diagnostic approach, which requires an invasive skin biopsy is associated with inherent risks and necessitates skilled healthcare practitioners in sterile settings. There is a critical need for a rapid, less invasive method for Leishmania detection. The main objective of this study was to evaluate and compare the diagnostic efficacy of PCR and qPCR in detecting PKDL, utilizing both skin and blood samples and to assess the utility of blood samples for molecular diagnosis. METHODS AND RESULTS: 73 individuals exhibiting clinical symptoms of PKDL and who had tested positive for rK39 rapid diagnostic test (RDT) were enrolled in this study. For the diagnosis of PKDL, both PCR and real-time quantitative PCR (qPCR), employing SYBR Green and TaqMan assays, were performed on blood and skin matched samples. qPCR results using both TaqMan and SYBR Green assay, indicated higher parasite loads in the skin compared to blood, as evident by the Ct values. Importantly, when blood samples were used for PKDL diagnosis by qPCR, an encouraging sensitivity of 69.35% (TaqMan assay) and 79.36% (SYBR Green) were obtained, compared to 8.2% with conventional PCR. CONCLUSION: The findings of the study suggest the potential utility of blood for molecular diagnosis by qPCR, offering a less invasive alternative to skin biopsies in field setting for the early detection of parasitaemia in PKDL patients and effective management and control of the disease.
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Leishmaniasis Cutánea , Leishmaniasis Visceral , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/sangre , Leishmaniasis Visceral/parasitología , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/sangre , Leishmaniasis Cutánea/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Masculino , Femenino , Adulto , Adolescente , Piel/parasitología , Piel/patología , Sensibilidad y Especificidad , Persona de Mediana Edad , Carga de Parásitos/métodos , Técnicas de Diagnóstico Molecular/métodos , Adulto Joven , Niño , ADN Protozoario/genética , ADN Protozoario/sangreRESUMEN
In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.
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Antibacterianos , Bencimidazoles , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Sulfonamidas , Bencimidazoles/farmacología , Bencimidazoles/química , Bencimidazoles/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Estructura Molecular , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Dihidropteroato Sintasa/antagonistas & inhibidores , Dihidropteroato Sintasa/metabolismo , Humanos , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Escherichia coli/efectos de los fármacosRESUMEN
Parasitic infections are a major global health issue causing significant mortality and morbidity. Despite substantial advances in the diagnostics and treatment of these diseases, the currently available options fall far short of expectations. From diagnosis and treatment to prevention and control, nanotechnology-based techniques show promise as an alternative approach. Nanoparticles can be designed with specific properties to target parasites and deliver antiparasitic medications and vaccines. Nanoparticles such as liposomes, nanosuspensions, polymer-based nanoparticles, and solid lipid nanoparticles have been shown to overcome limitations such as limited bioavailability, poor cellular permeability, nonspecific distribution, and rapid drug elimination from the body. These nanoparticles also serve as nanobiosensors for the early detection and treatment of these diseases. This review aims to summarize the potential applications of nanoparticles in the prevention, diagnosis, and treatment of parasitic diseases such as leishmaniasis, malaria, and trypanosomiasis. It also discusses the advantages and disadvantages of these applications and their market values and highlights the need for further research in this field.
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Malaria, caused by Plasmodium species, remains a major global health concern, causing millions of deaths annually. While the introduction of the RTS,S vaccine has shown promise, there is a pressing need for more effective vaccines due to the emergence of drug-resistant parasites and insecticide-resistant vectors. However, the complex life cycle and genetic diversity of the parasite, technical obstacles, limited funding, and the impact of the 2019 pandemic have hindered progress in malaria vaccine development. This review focuses on advancements in malaria vaccine development, particularly the ongoing clinical trials targeting antigens from different stages of the Plasmodium life cycle. Additionally, we discuss the rationale, strategies, and challenges associated with vaccine design, aiming to enhance the immune response and protective efficacy of vaccine candidates. A cost-effective and multistage vaccine could hold the key to controlling and eradicating malaria.
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A series of new quinoline derivatives has been designed, synthesized and evaluated as antibacterial and antifungal agents functioning as peptide deformylase enzyme (PDF) inhibitors and fungal cell wall disruptors on the basis of computational and experimental methods. The molecular docking and ADMET assessment aided in the synthesis of quinoline derivatives starting from 6-amino-4-methyl-1H-quinoline-2-one substituted with different types of sulfonyl/benzoyl/propargyl moieties. These newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity. Antibacterial screening of all compounds showed excellent MIC value (MIC, 50 - 3.12 µg/mL) against bacterial strains, viz. Bacillus cerus, Staphylococcus, Pseudomonas and Escherichia coli. Compounds 2 and 6 showed better activity. Fractional inhibitory concentration (FIC) values of compounds were lowered by 1/2 to 1/128 of the original MIC values when a combinatorial screening with reference drugs was performed. Further, antifungal screening against fungal strains, viz. A. flavus, A. niger, F. oxysporum and C. albicans also showed that all compounds were potentially active and compound 6 being the most potent. Further, the cytotoxicity experiments revealed that compound 6 was the least toxic molecule. The molecular dynamics (MD) simulation investigations elucidated the conformational stability of compound 6-PDF complex with flexible binding pocket residues. The highest number of stable hydrogen bonds with the PDF residues during the entire simulation time illustrated strong binding affinity of compound 6 with PDF.Communicated by Ramaswamy H. Sarma.
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A series of quinoline derivatives has been designed, synthesized and screened for their anti-HIV properties. The drug-like properties of compounds were evaluated first and then molecular docking using DS v20.1.0.19295 software showed that the compounds behaved as non-nucleoside reverse transcriptase inhibitors (NNRTIs) while interacting at the allosteric site of target HIV-RT protein (PDB:3MEC). The docking results revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Val179, Tyr188, Gln190, Gly190, Pro225, Phe227, and Tyr318, and showed π-interaction with Tyr188 and Tyr318. TOPKAT (Toxicity Prediction by Komputer Assisted Technology) results confirmed that the compounds were found to be less toxic than the reference drugs. Density functional theory (DFT) analysis was performed to assess the binding affinity of all compounds. Further, molecular dynamics (MD) simulations were performed on compound 6 and delavirdine with HIV-RT enzyme. Comprehensive MD analyses showed a similar pattern of conformational stability and flexibility in both the complexes suggesting alike inhibitory action. The hydrogen-bonding interactions and the binding energy of active-site residues for the compound 6 complex revealed strong inhibitory activity than the reference (delavirdine) complex. Thus, the compound 6 might act as a potential inhibitor against HIV-RT. Overall, this study revealed that compound 6 (5-hydroxy-N-(4-methyl-2-oxo-1,2-dihydroquinolin-8-yl) thiophene-2-sulfonamide) has prudent anti-HIV activity against both HIV-1 (SI = 2.65) and HIV-2 (SI = 2.32) that can further be utilised in drug discovery against HIV virus.
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Infecciones por VIH , Quinolinas , Dominio Catalítico , Delavirdina/uso terapéutico , Diseño de Fármacos , Transcriptasa Inversa del VIH/química , Humanos , Simulación del Acoplamiento Molecular , Quinolinas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Relación Estructura-ActividadRESUMEN
BACKGROUND: Infectious disease burden in India is among the largest in the world. Cephalosporins are being used extensively in the current scenario, both empirically and as definitive treatment. With this information, we tried to evaluate the prescription pattern of drugs for infections in medicine and general surgical wards of a tertiary care hospital and evaluate the utilization of cephalosporins in the same. METHODOLOGY: The study was conducted for a duration of 3 months in a tertiary care hospital after approval from the Institutional Ethics Committee, and permission of the respective heads of the surgery and medicine departments was obtained. After satisfying the inclusion criteria, participants' demographic details and the prescription notes by the treating doctor were noted and analyzed. The WHO prescription indicators were analyzed and the prescriptions were evaluated for the completeness of them. The utilization of cephalosporins was evaluated based on the institutional standard treatment guideline (STG) - Guidelines for Antimicrobial Therapy and Prophylaxis, 2014. Data were analyzed using descriptive statistics. RESULTS: A total of 600 patients were recruited, of which 350 were male and 250 were female. A total of 4341 drugs were prescribed. On an average, 7 drugs per prescription were found. The generic drugs prescribed were 27% (1163). Among the drugs prescribed, 19% (850) were antibiotics, of which 36.94% (314) were cephalosporins and 81% (3491) were other drugs. Ninety-four percent (565) prescriptions were incomplete (in terms of dose, frequency, duration, or dosage form). After referring to the STG, we found that cephalosporins were prescribed empirically in 40% (126) cases, of which medicine prescriptions accounted for it the most. CONCLUSION: Cephalosporins are extensively prescribed in medicine and surgery wards of the tertiary care hospital.
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A new series of quinoline derivatives has been designed and synthesized as probable protease inhibitors (PIs) against severe acute respiratory syndrome coronavirus 2. In silico studies using DS v20.1.0.19295 software have shown that these compounds behaved as PIs while interacting at the allosteric site of target Mpro enzyme (6LU7). The designed compounds have shown promising docking results, which revealed that all compounds formed hydrogen bonds with His41, His164, Glu166, Tyr54, Asp187, and showed π-interaction with His41, the highly conserved amino acids in the target protein. Toxicity Prediction by Komputer Assisted Technology results confirmed that the compounds were found to be less toxic than the reference drug. Further, molecular dynamics simulations were performed on compound 5 and remdesivir with protease enzyme. Analysis of conformational stability, residue flexibility, compactness, hydrogen bonding, solvent accessible surface area (SASA), and binding free energy revealed comparable stability of protease:5 complex to the protease: remdesivir complex. The result of hydrogen bonding showed a large number of intermolecular hydrogen bonds formed between protein residues (Glu166 and Gln189) and ligand 5, indicating strong interaction, which validated the docking result. Further, compactness analysis, SASA and interactions like hydrogen-bonding demonstrated inhibitory properties of compound 5 similar to the existing reference drug. Thus, the designed compound 5 might act as a potential inhibitor against the protease enzyme.Communicated by Ramaswamy H. SarmaHighlightsQuinoline derivatives have been designed as protease inhibitors against SARS-CoV-2.The compounds were docked at the allosteric site of SARS-CoV-2-Mpro enzyme (PDB ID: 6LU7) to study the stability of protein-ligand complex.Docking studies indicated the stable ligand-protein complexes for all designed compounds.The Toxicity Prediction by Komputer Assisted Technology protocol in DS v20.1.0.19295 software was used to evaluate the toxicity of the designed quinoline derivatives.Molecular dynamics studies indicated the formation of stable ligand-Mpro complexes.
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Antivirales , Inhibidores de Proteasas , Quinolinas , SARS-CoV-2 , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Péptido Hidrolasas , Inhibidores de Proteasas/farmacología , SARS-CoV-2/efectos de los fármacos , Quinolinas/farmacología , Antivirales/farmacologíaRESUMEN
A series of new N-1-(ß-d-ribofuranosyl) benzimidazole derivatives has been designed using in silico methods and synthesized as probable antimicrobial agents. Further, the compounds were assessed for their antibacterial and antifungal activity. Antibacterial screening was done by employing broth micro-dilution method and compounds exhibited excellent inhibitory activity (MIC, 50-1.56 µg/mL) against different human pathogenic bacteria, viz. B. cerus, B. subtilis, S. aureus, E. coli and P. aeruginosa and drug resistant strain (DRS) of E. coli. A great synergistic effect was observed during evaluation of ∑FIC, where a combination study was performed using standard references, viz. chloramphenicol and kanamycin. The MIC data obtained from different methods of combination approach revealed 4-128 fold more potency compared to compounds tested alone. The results clearly indicated the possibility of these compounds as active ingredients of drug regimen used against MDR strains. Antifungal screening were also performed employing two different methods, viz. serial dilution method and zone inhibition method, clearly indicated that compounds were also potentially active against several species of pathogenic fungal strains, viz. A. flavus, A. niger, F. oxysporum and C. albicans. The assessment of structure activity relationship (SAR) clearly revealed that presence of less polar and more hydrophobic substituents positively favours the antibacterial activity, conversely, more polar and hydrophilic substituents favours the antifungal activities. Thus, the results positively endorsed the compounds as potent antibacterial and antifungal agents which could be developed as possible drug regimens.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Bencimidazoles/farmacología , Hongos/efectos de los fármacos , Nucleósidos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Bencimidazoles/síntesis química , Bencimidazoles/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Nucleósidos/síntesis química , Nucleósidos/química , Relación Estructura-ActividadRESUMEN
In view of the low toxicity of NNRTIs in comparison to NRTIs, a new series of diarylpyrimidine derivatives has been designed as NNRTIs against HIV-1. In silico studies using DS 3.0 software have shown that these compounds behaved as NNRTIs while interacting at the allosteric site of HIV-RT. The designed compounds have shown promising docking results, which revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Tyr181, Tyr318 and π- interactions with Tyr181, Tyr188, Phe227 and Trp229 amino acid residues located in the non-nucleoside inhibitor binding pocket (NNIBP) of HIV-RT protein. The intended molecules have shown high binding affinity with HIV-1 RT, analogous to standard drug molecule-etravirine. TOPKAT results confirmed that the designed compounds were found to be less toxic than the reference drug. Further, employing molecular dynamics simulations, the complexes of the best screened compound 6 and etravirine with the HIV-1 RT protein were analyzed by calculating the RMSD, RMSF, Rg, number of hydrogen bonds, principal components of the coordinates, molecular mechanics-Poisson-Boltzmann surface area-based binding free energy and their decomposition for different interactions. The analysis demonstrated the higher stability of compound 6 than the standard drug etravirine with HIV-1 RT. The interactions like hydrogen-bonding, van-der-Waals, electrostatic and the solvent accessible surface energy have favorable contributions to the complex stability. Thus, the shortlisted designed compound has great promise as a potential inhibitor against HIV-1 RT.
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Fármacos Anti-VIH , Inhibidores de la Transcriptasa Inversa , Fármacos Anti-VIH/farmacología , Sitios de Unión , Diseño de Fármacos , Transcriptasa Inversa del VIH , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Inhibidores de la Transcriptasa Inversa/farmacologíaRESUMEN
OBJECTIVE: The objective of the present research was to evaluate the prescription pattern of the drugs used in the pharmacological treatment of cancer-related neuropathic pain (CRNP) and to assess the adherence of the physicians to the Neuropathic Pain Special Interest Group (NeuPSIG) Guidelines. MATERIALS AND METHODS: This was a cross-sectional, observational study where patients who presented to the pain and palliative care outpatient clinic of the tertiary care hospital with CRNP were prospectively recruited. Participants were screened for neuropathic pain using DN4 questionnaire. Demographic details, diagnosis, medication details, and adherence to NeuPSIG guidelines were assessed using a validated questionnaire. RESULTS: Of 300 patients screened, 64% were male and 36% were female, with a mean age of 48.26 ± 13.05 years. The predominant symptoms found were pin-and-needle sensation (99%) followed by tingling sensation (98.66%). The most common diagnosis was head-and-neck cancers (37.3%) followed by bone cancers (17.3%) and lung cancers (15.3%). Among the first-line drugs recommended in NeuPSIG for CRNP, pregabalin (78.7%) was the most common drug prescribed followed by amitriptyline (67%). The most common co-prescribed drugs were acid suppressants drugs (50.7%). Tapentadol, which is not part of the NeuPSIG guidelines, was prescribed on 51 occasions for neuropathic pain. Underdosing was observed in 272 prescriptions. Only 12 prescriptions completely adhered, while 275 had partial, and 13 prescriptions had poor adherence to NeuPSIG guidelines. CONCLUSION: The most commonly used drugs in the treatment of CRNP were pregabalin and amitriptyline. Most physician partially or did not adhere to the NeuPSIG guideline in the management of CRNP.
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A series of 2-Cl-benzimidazole derivatives was synthesized and assessed for antibacterial activity. Antibacterial results indicated that compounds 2d, 2e, 3a, 3b, 3c, 4d and 4e showed promising activity against B. cerus, S. aureus and P. aeruginosa (MIC: 6.2⯵g/mL) and excellent efficacy against E. coli (MIC: 3.1⯵g/mL). Furthermore, compounds 3d and 3e displayed better activity (MIC: 3.1⯵g/mL) than the reference drugs chloramphenicol and cycloheximide against gram positive and gram negative bacterial strains. The compounds 3d-e also showed better activity than the reference drug paromomycin against B. cerus and P. aeruginosa and showed similar inhibition pattern against S. aureus and E. coli. (MIC: 3.1⯵g/mL). Studies on fractional inhibitory concentration (FIC) determination of compounds 1a-e, 2a-c, 4a-c and the reference antibiotic via combination approach revealed a synergistic effect as the MIC values were lowered up to 1/8th to 1/33rd of the original MIC. In-vitro cytotoxicity study indicated that 2-Cl-benzimidazole derivatives showed less toxicity than the reference used against PBM, CEM and Vero cell lines. Docking studies and MD simulations of compounds on bacterial protein (eubacterial ribosomal decoding A site, PDB: 1j7t) have been conducted to find the possible mode of action of the molecules. In silico ADMET evaluations of compounds 3d and 3e showed promising results comparable to the reference drugs used in this study.
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Antibacterianos/farmacología , Bencimidazoles/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/metabolismo , Antibacterianos/toxicidad , Bacillus cereus/efectos de los fármacos , Bencimidazoles/síntesis química , Bencimidazoles/metabolismo , Bencimidazoles/toxicidad , Línea Celular , Cloranfenicol/farmacología , Chlorocebus aethiops , Cicloheximida/farmacología , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Humanos , Ligandos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Paromomicina/farmacología , Unión Proteica , Pseudomonas aeruginosa/efectos de los fármacos , ARN Ribosómico 16S/metabolismo , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A new series of heterocyclic molecules bearing sulfonamide linkage has been synthesized and screened for antibacterial activity. During antibacterial screening using broath dilution method, molecules were found to be highly active (MIC value 50-3.1⯵g/mL) against different human pathogens, namely B. cerus, S. aureus, E. coli and P. aeruginosa, and most effective against E. coli. A great synergistic effect was observed during determination of FIC where molecules were used in combination with reference drugs chloramphenicol and sulfamethoxazole. The MIC value of the combination - varying concentration of test compounds and ½ MIC of reference drugs or varying concentration of reference drugs and ½ MIC of test compounds, was reduced up to 1/4 or 1/32 of the original value, indicating thereby the combination was 4-32 times more potent than the test molecule. The molecules also showed low degree of cytotoxicity against PBM, CEM and VERO cell lines. The results positively indicated towards the development of lead antibacterials using the combination approach.
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Antibacterianos/síntesis química , Simulación del Acoplamiento Molecular , Sulfonamidas/química , Animales , Antibacterianos/química , Antibacterianos/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Bencimidazoles/química , Benzotiazoles/química , Sitios de Unión , Dominio Catalítico , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Diseño de Fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Indazoles/química , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Sulfametoxazol/farmacología , Sulfonamidas/síntesis química , Tiazoles/química , Células VeroRESUMEN
BACKGROUND: The management of ventricular electrical storm can prove to be a challenge for the clinician given its complexity and life threatening consequences. CASE CHARACTERISTICS: 8-year-old boy with repeated life-threatening polymorphic ventricular tachycardia following aortic valve replacement surgery. INTERVENTION: Defibrillated 45 times in addition to multiple antiarrhythmic drugs. OUTCOME: Conversion to stable sinus rhythm with normal neurological outcome. MESSAGE: Electric storm can be controlled by combination of multiple intravenous antiarrhythmic drugs.
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Taquicardia Ventricular , Disfunción Ventricular Izquierda , Válvula Aórtica/cirugía , Enfermedad de la Válvula Aórtica Bicúspide , Niño , Cardiopatías Congénitas/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , ReoperaciónRESUMEN
CONTEXT: Reports of successful use of vasopressin in various shock states and cardiac arrest has lead to the emergence of vasopressin therapy as a potentially major advancement in the management of critically ill children. OBJECTIVE: To provide an overview of physiology of vasopressin, rationale of its use and dose schedule in different disease states with special focus on recent advances in the therapeutic applications of vasopressin. DATA SOURCE: MEDLINE search (1966-September 2011) using terms vasopressin, terlipressin, arginine-vasopressin, shock, septic shock, vasodilatory shock, cardiac arrest, and resuscitation for reports on vasopressin/terlipressin use in children and manual review of article bibliographies. Search was restricted to human studies. Randomized controlled trials, cohort studies, evaluation studies, case series, and case reports on vasopressin/terlipressin use in children (preterm neonates to 21 years of age) were included. Outcome measures were analysed using following clinical questions: indication, dose and duration of vasopressin/terlipressin use, main effects especially on systemic blood pressure, catecholamine requirement, urine output, serum lactate, adverse effects, and mortality. RESULTS: 51 reports on vasopressin (30 reports) and terlipressin (21 reports) use in pediatric population were identified. A total of 602 patients received vasopressin/terlipressin as vasopressors in various catecholamine-resistant states (septic - 176, post-cardiotomy - 136, other vasodilatory/mixed shock - 199, and cardiac arrest - 101). Commonly reported responses include rapid improvement in systemic blood pressure, decline in concurrent catecholamine requirement, and increase in urine output; despite these effects, the mortality rates remained high. CONCLUSION: In view of the limited clinical experience, and paucity of randomized controlled trials evaluating these drugs in pediatric population, currently no definitive recommendations on vasopressin/terlipressin use can be laid down. Nevertheless, available clinical data supports the use of vasopressin in critically ill children as a rescue therapy in refractory shock and cardiac arrest.
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Paro Cardíaco/tratamiento farmacológico , Choque/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Adulto JovenRESUMEN
Fever in the postoperative period in children undergoing surgery for congenital heart disease is fairly common and tends to cause anxiety to both the surgeon and the patient. Such fever is associated with the metabolic response to trauma, systemic response to the cardiopulmonary bypass, hypothermia, presence of drainage tubes, drugs, blood transfusion as well as infections. Establishing the diagnosis requires proper assessment of the patient with focused history, targeted physical examination and judicious use of investigations with the knowledge of the common causes.
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OBJECTIVE: To assess the efficacy of arginine vasopressin (AVP) as a rescue therapy in children with catecholamine refractory vasodilatory shock and its effect on various hemodynamic, clinical, and laboratory variables. METHODS: This prospective hospital based study was conducted from January 2008 through July 2008 at a tertiary pediatric cardiac critical care unit. Twelve post cardiac surgery patients with advanced vasodilatory shock requiring intravenous vasopressin infusion longer than 60 min were included and continuous vasopressin infusion was given. The primary outcome measures were restoration of Mean arterial blood pressure (MAP) after starting AVP infusion and decrease in other concurrent catecholamines requirement. The secondary outcome measures were survival to hospital discharge, adverse effects, and laboratory variables. RESULTS: Vasopressin was infused in the dose range of 0.0005 to 0.003 units/kg/min for a mean duration of 55.6 h. MAP improved from 41.08 ± 6.15 mmHg at baseline to 48.92 ± 10.05 mmHg after 1 h (P < 0.05), to 57.01 ± 8.30 mmHg after 4 h of AVP infusion (P < 0.001), and to 62.33 ± 8.55 mmHg after 12 h (P < 0.001), which further increased to 71.75 ± 9.55 mmHg after 24 h (P < 0.001). Inotrope score and requirement of other concurrent inotropes declined significantly in all patients after starting AVP infusion (P < 0.001). Lactate levels also declined significantly (P < 0.0001). No significant adverse effect due to end organ ischemia was observed. Only one patient expired while on vasopressin infusion due to refractory hypotension. CONCLUSIONS: Concurrent addition of vasopressin at an appropriate stage help improving MAP significantly with decreased dependence on high dose catecholamines without any significant adverse effects.
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Arginina Vasopresina/administración & dosificación , Países en Desarrollo , Cardiopatías Congénitas/cirugía , Hemodinámica/efectos de los fármacos , Complicaciones Posoperatorias/tratamiento farmacológico , Choque/tratamiento farmacológico , Vasoconstrictores/administración & dosificación , Vasodilatación/efectos de los fármacos , Arginina Vasopresina/efectos adversos , Catecolaminas/administración & dosificación , Catecolaminas/efectos adversos , Niño , Preescolar , Resistencia a Múltiples Medicamentos , Femenino , Humanos , India , Lactante , Infusiones Intravenosas , Masculino , Estudios Prospectivos , Vasoconstrictores/efectos adversosRESUMEN
Pediatric cardiac surgery is undergoing a metamorphosis, with more and more critical patients being operated in our country today. Although the principles of physiology have not changed, it is imperative that care providers continue to stay abreast with developments and newer drugs that may help modify the outcome. The team dynamics have also become more complex, which necessitates the need for all care providers (surgeons, cardiologists, anesthesiologists, and intensivists) to better understand the interactions and benefits of newer drugs. Vasopressin has been used in our adult patients for more than a decade and recently has found its rightful place in the pediatric armoury. The objective of this article is to review the physiology of vasopressin and the rationale of its use in critically ill children with shock, in context of the available published data.