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Increased alcohol intake over decades leads to progressive alcohol-related liver disease (ALD) and contributes to increased mortality. It is characterized by reduced platelet count. Platelets have a role in protecting vascular integrity and involved in liver regeneration. Alcohol affects the platelet count and its function. Platelet function is regulated by their proteins, released during pathophysiological conditions. Therefore, platelet proteome plays a vital role during ALD. This preliminary study consists of 10 patients with ALD. It includes the preparation of human platelets for the proteomic approach. We performed liquid chromatography-mass spectrometry for the samples. A total of 536 proteins were identified in patients with ALD of which 31 proteins were mentioned as a candidate based on their clinical significance. The advancement of diagnostic or therapeutic tools based on the application of platelet proteins in ALD is still far off. Platform for platelet and its proteome research may give diagnostic and prognostic insights into ALD. Platelet proteomes could possibly be concluded as therapeutic and potential diagnostic or prognostic markers in ALD. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01120-9.
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In light of the updated Eatwell Guide and the corresponding change in the consumption of fruit smoothies, the aim of this study was to measure the glycaemic index and load of two commercial fruit smoothies and to investigate the retention of dietary fibre following production. In vitro analysis was performed to identify fibre material (cellulose and pectins) using calcofluor staining and immunocytochemical labelling. A repeated measures cross-over study was conducted (n 10) to determine the glycaemic index (GI) and glycaemic load (GL) of the smoothies. Results showed that dietary fibre was still present in the smoothies after processing (16.9-17.5% cellular material by dry weight). The GI was low for both smoothies (39 and 36), whereas the GL was medium and borderline-low, respectively (11.4 and 9.7). The retention of fibre in these smoothies may have a potential positive effect on glycaemic response and may contribute to daily fibre requirements.
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Bebidas/análise , Glicemia/metabolismo , Carboidratos da Dieta/metabolismo , Fibras na Dieta/análise , Frutas , Índice Glicêmico , Carga Glicêmica , Adulto , Comércio , Estudos Cross-Over , Feminino , Manipulação de Alimentos , Humanos , Masculino , Adulto JovemRESUMO
Background: Hypergenetic molars are uncommon in children and adolescents. Furthermore, the presence of multiple eumorphic supernumerary molars (SNMs) in children is sporadic. The author, therefore, reports a nonsyndromic case of multiple supplemental SNMs in a child. Case description: A ten year old boy primarily complaining of cheek biting was found to have six molars on the maxillary left quadrant. Following investigations and case discussion, four molars and fibroma were surgically removed under general anesthesia. Discussion: This paper discusses the prevalence and management of SNMs in the pediatric population while documenting the first case of multiple eumorphic SNMs in the mixed dentition. How to cite this article: Venkatesh SP. Pediatric Molar Hyperdontia: A Descriptive Case Report. Int J Clin Pediatr Dent 2023;16(5):763-768.
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IgA nephropathy (IgAN) is one of the most common glomerulonephritides. The disease is characterized by haematuria, proteinuria, deposition of galactose-deficient IgA1 in the glomerular mesangium and mesangial hypercellularity, further leading to extracellular matrix expansion. Kidney biopsy is the gold standard for IgAN diagnosis. Due to the invasiveness of renal biopsy, there is an unmet need for noninvasive biomarkers to diagnose and estimate the severity of IgAN. Understanding the role of RNA molecules as genetic markers to target diseases may allow developing therapeutic and diagnostic markers. In this review we have focused on intrarenal, extrarenal and extracellular noncoding RNAs involved in the progression of IgAN. This narrative review summarizes the pathogenesis of IgAN along with the correlation of noncoding RNA molecules such as microRNAs, small interfering RNAs, circular RNAs and long non-coding RNAs that play an important role in regulating gene expression, and that represent another type of regulation affecting the expression of specific glycosyltranferases, a key element contributing to the development of IgAN.
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Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/diagnóstico , Imunoglobulina A/metabolismo , Mesângio Glomerular/patologia , RNA não TraduzidoRESUMO
To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.
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Desnutrição , Adulto , Humanos , Índia/epidemiologiaRESUMO
Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.
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Pesquisa Biomédica , Tuberculose , Humanos , Índia , Tuberculose/prevenção & controle , Programas Governamentais , OrganizaçõesRESUMO
The quantum mechanical density functional theory (DFT) approach was used to analyze vibrational spectroscopy for the title compound 2-chloroquinoline-3-carboxaldehyde, and the observations were compared to experimental results. B3LYP with the 6-311++ G (d, p) basis set produces the optimized molecular structure and vibrational assignments. The charge delocalization and hyper conjugative interactions were studied using NBO analysis. Fukui functions were used to determine the chemical reactivity of the examined molecule. The linear polarizability, first order polarizability, NLO and Thermodynamic properties are calculated. Additionally, Molecular electrostatic potential (MEP) and HOMO-LUMO are reported. Multi wavefunction analysis like ELF (Electron Localization Function) and LOL (Localized Orbital Locator) are analyzed. For the headline compound, drug-likeness properties were examined. Molecular docking analysis on the examined molecule are done to understand the biological functions of the headline molecule and the minimum binding energy, hydrogen bond interactions, are analyzed.
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Children are particularly a challenging group of patients when trying to ensure the safe use of medicines. Their variable weight, body surface area and organ system maturity affect their ability to metabolize and excrete medications. In addition, there are few standardized dosing regimens for children, with most medication dosing requiring body weight calculations. These challenges in pediatric medication use contribute to an increased risk of medication errors including serious drug dosing errors. This manuscript addresses the pediatric dentists to focus on the issues related to pediatric medication.
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Erros de Medicação/prevenção & controle , Preparações Farmacêuticas/administração & dosagem , Superfície Corporal , Peso Corporal , Criança , Formas de Dosagem , Cálculos da Dosagem de Medicamento , Prescrições de Medicamentos , Humanos , Preparações Farmacêuticas/metabolismo , SegurançaRESUMO
Genome wide microsatellite maps shall support Phytophthora systematics through the development of reliable markers, enabling species discrimination and variability analyses. Whole genome sequences of 17 Phytophthora accessions belonging to 14 species were retrieved from GenBank and the genome-wide microsatellites in each species were mined. A total of 51,200 microsatellites, including dinucleotide to decanucleotide motifs, have been identified across all the species and each one was characterized for uniqueness and repeat number. The P. infestans T30-4 genome had the highest (6873) and P. multivora 3378 had the lowest number of microsatellites (1802). Dinucleotide motifs (63.6%) followed by trinucleotide motifs (30.1%) were most abundant in all the genome. From 14 species, 250 microsatellites which are unique for the respective genomes are detailed along with their primer combinations and product sizes. P. sojae had the highest number of unique microsatellite motifs. Genome wide microsatellite maps for all the 14 Phytophthora species including the chromosome, position, motif, repeat number, forward and reverse primer sequences and expected PCR product size, for every microsatellite are presented. Markers based on the unique microsatellites could be used to identify each species, whereas the ones common to all species could be used to identify the genetic variability. Furthermore, to confirm the results, pure cultures of P. capsici, P. nicotianae and P. palmivora were procured from the Phytophthora Repository, DNA was isolated and the unique markers were screened across the species. The characteristic markers developed have confirmed the genome analysis results.
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The current study evaluated a new series of N,N'-alkane-diyl-bis-3-picolinium (bAPi) analogs with C6-C12 methylene linkers as nicotinic acetylcholine receptor (nAChR) antagonists, for nicotine-evoked [3H]dopamine (DA) overflow, for blood-brain barrier choline transporter affinity, and for attenuation of discriminative stimulus and locomotor stimulant effects of nicotine. bAPi analogs exhibited little affinity for alpha4beta2* (* indicates putative nAChR subtype assignment) and alpha7* high-affinity ligand binding sites and exhibited no inhibition of DA transporter function. With the exception of C6, all analogs inhibited nicotine-evoked [3H]DA overflow (IC50 = 2 nM-6 microM; Imax = 54-64%), with N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; C12) being most potent. bPiDDB did not inhibit electrically evoked [3H]DA overflow, suggesting specific nAChR inhibitory effects and a lack of toxicity to DA neurons. Schild analysis suggested that bPiDDB interacts in an orthosteric manner at nAChRs mediating nicotine-evoked [3H]DA overflow. To determine whether bPiDDB interacts with alpha-conotoxin MII-sensitive alpha6beta2-containing nAChRs, slices were exposed concomitantly to maximally effective concentrations of bPiDDB (10 nM) and alpha-conotoxin MII (1 nM). Inhibition of nicotine-evoked [3H]DA overflow was not different with the combination compared with either antagonist alone, suggesting that bPiDDB interacts with alpha6beta2-containing nAChRs. C7, C8, C10, and C12 analogs exhibited high affinity for the blood-brain barrier choline transporter in vivo, suggesting brain bioavailability. Although none of the analogs altered the discriminative stimulus effect of nicotine, C8, C9, C10, and C12 analogs decreased nicotine-induced hyperactivity in nicotine-sensitized rats, without reducing spontaneous activity. Further development of nAChR antagonists that inhibit nicotine-evoked DA release and penetrate brain to antagonize DA-mediated locomotor stimulant effects of nicotine as novel treatments for nicotine addiction is warranted.
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Comportamento Animal/efeitos dos fármacos , Dopamina , Nicotina/farmacologia , Antagonistas Nicotínicos/farmacologia , Picolinas/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Transporte Biológico Ativo , Barreira Hematoencefálica/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Aprendizagem por Discriminação/efeitos dos fármacos , Dopamina/metabolismo , Masculino , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Antagonistas Nicotínicos/química , Antagonistas Nicotínicos/farmacocinética , Picolinas/química , Picolinas/farmacocinética , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/metabolismo , Ligação Proteica , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
Fructooligosaccharides (FOSs) were prepared from sucrose using fungal fructosyl transferase (FTase) obtained from Aspergillus oryzae MTCC 5154. The resulting mixture consisted of glucose (28-30%), sucrose (18-20%) and fructooligosaccharides (50-54%) as indicated by HPLC analysis. Identification of oligomers present in the mixture of fructooligosaccharides was carried out using NMR spectroscopy and LC-MS. No compounds other than mono-, di-, tri-, tetra- and pentasaccharides were identified in the FOS mixture prepared using FTase. NMR and LC-MS spectra proved the absence of any toxic microbial metabolites of Aspergillus species in FOS thereby emphasizing its safe use as a food ingredient. Animal studies conducted on streptozotocin-induced diabetic rats suggested that the use of FOS as an alternative non-nutrient sweetener is without any adverse effects on various diabetes-related metabolic parameters. Despite the high free-sugar content associated with it, FOS did not further aggravate the hyperglycemia and glucosuria in diabetic animals, even at 10% levels. On the other hand, by virtue of its soluble fibre effect, it has even alleviated diabetic-related metabolic complications to a certain degree.
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Frutose/química , Oligossacarídeos/química , Edulcorantes/química , Animais , Aspergillus/enzimologia , Diabetes Mellitus , Aditivos Alimentares/química , Hexosiltransferases/metabolismo , Hiperglicemia/dietoterapia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Oligossacarídeos/administração & dosagem , Ratos , Sacarose/metabolismo , Edulcorantes/administração & dosagemRESUMO
A 40 kg crossbred calf of one month age was presented to the Institute Referral Polyclinic, with a history of dysuria, stranguria along with a fluctuant swelling in the mid-perineal region. On physical examination, a diverticulum was observed which on aspiration revealed urine. It was reported that urine outflow was from a tiny orifice at the proposed natural site of the vulva. Dissection of the skin over the diverticulum revealed hypoplastic penis with adhesion of the preputeal sheath along with penile hypospadia. Permanent perineal urethrostomy and diverticulectomy was performed in the region of the defect. The urethral layer was sutured along with the skin using 1-0 Polyamide sutures in a simple interrupted pattern. No postoperative complication was reported till one year of surgery and animal was urinating properly.
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A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [(3)H]dopamine release from superfused rat striatal slices and for inhibition of [(3)H]nicotine and [(3)H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [(3)H]dopamine release with an IC(50) of 0.2 nM and I(max) of 67%.
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Compostos Aza/síntese química , Compostos Aza/farmacologia , Nicotina/metabolismo , Antagonistas Nicotínicos/síntese química , Antagonistas Nicotínicos/farmacologia , Compostos de Amônio Quaternário/química , Receptores Nicotínicos/metabolismo , Animais , Compostos Aza/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Estrutura Molecular , Antagonistas Nicotínicos/química , Ratos , Sais/química , Relação Estrutura-Atividade , Trometamina/químicaRESUMO
Cerium oxide nanoparticles (CeO2 NPs) are favorable in nanotechnology based on some remarkable properties. In this study, the crystalline CeO2 NPs are successfully prepared by an efficient microwave combustion (MCM) and conventional route sol-gel (CRSGM) methods. The structural morphology of the as-prepared CeO2 NPs was investigated by various spectroscopic and analytical techniques. Moreover, the XRD pattern confirmed the formation of CeO2 NPs as a face centered cubic structure. The magnetometer studies indicated the low saturation magnetization (23.96 emu/g) of CeO2 NPs for weak paramagnetic and high saturation magnetization (32.13 emu/g) of CeO2 NPs for super paramagnetic. After that, the oxidation effect of benzyl alcohol was investigated which reveals good conversion and selectivity. Besides, the CeO2 NPs modified glassy carbon electrode (GCE) used for the detection of nitrite with linear concentration range (0.02-1200 µM), low limit of detection (0.21 µM) and higher sensitivity (1.7238 µAµM-1 cm-2). However, the CeO2 NPs modified electrode has the fast response, high sensitivity and good selectivity. In addition, the fabricated electrode is applied for the determination of nitrite in various water samples. Eventually, the CeO2 NPs can be regarded as an effective way to enhance the catalytic activity towards the benzyl alcohol and nitrite.
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AIM: The aim of this study was to generate composite bone graft and investigate the rabbit fetal osteoblasts adhesion, proliferation and penetration on acellular matrices of cancellous bone. MATERIALS AND METHODS: Acellular cancellous bone was prepared and developed as in the previous study with little modification. These matrices were decellularized by rapid freeze and thaw cycle. To remove the cell debris, they were then treated with hydrogen peroxide (3%) and ethanol to remove antigenic cellular and nuclear materials from the scaffold. Primary osteoblast cells were harvested from 20 to 22 days old rabbit fetal long and calvarial bone. These cells were cultured and characterized using a specific marker. The third passaged fetal osteoblast cells were then seeded on the scaffold and incubated for 14 days. The growth pattern of the cells was observed. Scanning electron microscope and hematoxylin and eosin staining were used to investigate cells proliferation. RESULTS: The cells were found to be growing well on the surface of the scaffold and were also present in good numbers with the matrix filopodial extensions upto inside of the core of the tissue. CONCLUSION: Thus, a viable composite scaffold of bone could be developed which has a great potential in the field of bone tissue engineering.
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Coconut oil (CO), the primary choice of cooking purposes in the south Asian countries, is rich in medium chain saturated fatty acids, especially lauric acid (50-52%). The oil has high medicinal use in Ayurvedic system and known to contain polyphenolic antioxidants. Studies have reported that CO improves insulin sensitivity and shows hypoglycemic effect. However, there is no information regarding its effect on chronic diabetic complications including retinopathy and nephropathy is available. The secondary diabetic complications are mediated by the activation of polyol pathway, where aldose reductase (AR) plays crucial role. In this study, in silico analysis has been used to screen the effect of CO as well as its constituents, MCFAs and phenolic compounds, for targeting the molecules in polyol pathway. The study revealed that lauric acid (LA) interacts with AR and DPP-IV of polyol pathway and inhibits the activity of these enzymes. Validation studies using animal models confirmed the inhibition of AR and SDH in wistar rats. Further, the LA dose dependently reduced the expression of AR in HCT-15 cells. Together, the study suggests the possible role of CO, particularly LA in reducing secondary diabetic complications.
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Óleo de Coco/uso terapêutico , Nefropatias Diabéticas/dietoterapia , Retinopatia Diabética/dietoterapia , Ácidos Graxos/uso terapêutico , Aldeído Redutase/química , Aldeído Redutase/metabolismo , Animais , Antioxidantes/uso terapêutico , Óleo de Coco/química , Nefropatias Diabéticas/patologia , Retinopatia Diabética/patologia , Humanos , Ácidos Láuricos/química , Ácidos Láuricos/uso terapêutico , Ayurveda , Polímeros/química , Polifenóis/química , Polifenóis/uso terapêutico , RatosRESUMO
Bacillus thuringiensis is the major source for transfer of genes to impart insect resistance in transgenic plants. Cry2A proteins of B. thuringiensis are promising candidates for management of resistance development in insects owing to their difference from the currently used Cry1A proteins, in structure and insecticidal mechanism. The cry2Ab gene was found to lack a functional promoter and, hence, is cryptic in nature. The cry2Ab7 gene was cloned from a new indigenous B. thuringiensis strain, 14-1. Nucleotide sequencing of the cry2Ab gene cloned from B. thuringiensis strain 14-1 revealed an open reading frame of 1902 bp. The deduced amino acid sequence of Cry2Ab of B. thuringiensis strain 14-1 showed a variation in three amino acid residues in comparison to the holotype sequence, Cry2Ab1. Expression of the newly cloned cry2Ab gene was studied in an acrystalliferous strain of B. thuringiensis (4Q7) by fusing the cry2Ab gene downstream of cry2Aa promoter and orf1 + orf2 sequences. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of a spore-crystal mixture obtained from transformants of B. thuringiensis strain 4Q7 showed production of Cry2Ab protein of about 65 kDa. Alkali solubilized Cry2Ab7 protein showed toxicity against Helicoverpa armigera neonates.
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Bacillus thuringiensis/genética , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Endotoxinas/genética , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Sequência de Aminoácidos , Animais , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Sequência de Bases , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Endotoxinas/metabolismo , Proteínas Hemolisinas , Lepidópteros/metabolismo , Dados de Sequência Molecular , Peso Molecular , Plantas Geneticamente ModificadasRESUMO
A novel pyridine derivative, 3,5-bis-(1-methyl-pyrrolidin-2-yl)-pyridine, and a pair of diastereomers of 1,1'-dimethyl-[2,3']bipyrrolidinyl were isolated from the root of Nicotiana tabacum plants and identified as novel alkaloids by GC-MS analysis. The structures of these new alkaloids were confirmed by total synthesis. The affinities of these novel alkaloids, and other structurally related compounds for alpha4beta2*, alpha7* neuronal nicotinic acetylcholine receptors (nAChRs), and for nAChRs mediating nicotine-evoked dopamine release from rat striatum were also assessed. The results indicate that these compounds do not interact with alpha7* nAChRs, but inhibit [3H]nicotine binding to the alpha4beta2* nAChR subtype. The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum.
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Alcaloides/química , Alcaloides/farmacologia , Nicotiana/química , Receptores Nicotínicos/efeitos dos fármacos , Alcaloides/síntese química , Animais , Ligação Competitiva/efeitos dos fármacos , Dopamina/metabolismo , Humanos , Nicotina/metabolismo , Raízes de Plantas/químicaRESUMO
Several anti-cancer drugs are known to bring about their tumoricidal actions by a free radical dependent mechanism. Majority of the studies reported that adriamycin, mitomycin C, bleomycin, etc., augment free radical generation and lipid peroxidation process in vitro. Our results reported here suggest that following chemotherapy both stimulated and unstimulated human polymorphonuclear leukocytes generate increased amounts of superoxide anion and hydrogen peroxide. This was accompanied by increased formation of lipid peroxidation products as measured by thiobarbituric acid assay. These results confirm that many anti-cancer drugs augment free radical generation and lipid peroxidation even in an vivo situation.
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Antineoplásicos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Oxigênio/metabolismo , Adulto , Idoso , Criança , Feminino , Radicais Livres , Humanos , Peróxido de Hidrogênio/sangue , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Superóxidos/sangueRESUMO
The mechanism(s) involved in the generation of free radicals in human leukocytes by cis-unsaturated fatty acids, gamma-linolenic acid (GLA), and arachidonic acid (AA), was investigated. Calmodulin antagonists, chlorpromazine and trifluoperazine, inhibited free radical generation by human leukocytes in vitro induced by GLA, AA PMA (Phorbol myristate acetate), formyl-methionyl-leucyl-phenylalanine (FMLP) and lipopolysaccharide (LPS). On the other hand, chloroquine, a phospholipase A2 inhibitor, and colchicine, a microtubule disrupting agent, were without any effect. When sub-optimal concentrations of GLA and AA were added together, leukocytes showed an additive effect on free radical generation. These results indicate that Calmodulin dependent event(s) play a significant role in the generation of free radicals by human leukocytes.