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There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin catechin apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin cinnamic acid catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.

Background: Typhoid fever is a serious public health problem. It causes severe systemic infection in lesser developed areas of the world. Although blood culture is regarded as the gold standard for diagnosis, it is a time taking procedure. An early and accurate diagnosis is necessary for an effective treatment. Aims: The present study was done to comparatively evaluate rapid card and Widal slide agglutination tests for rapid diagnosis of typhoid cases. Settings and Design: The study design was a cross-sectional descriptive study done over a period of 6 months from January to June 2018. Materials and Methods: A total of 265 patients suspected of typhoid fever who gave their consent were included in the study whose blood samples were tested by both rapid card and Widal slide agglutination tests. Statistical Analysis Used: The collected data were analyzed using SPSS Data Editor Software version 20. Percentage of variables was calculated. Results: Of 265 patients, 97 patients were positive by the Widal slide test, whereas 113 patients were positive by the rapid card test, with 96.9% sensitivity and 88.7% specificity. Of 113 positives, 83 cases were positive for immunoglobulin M (IgM) only, whereas 30 cases were positive for both IgM and IgG. Conclusion: Rapid card test is a simple and easy to perform the diagnostic test for rapid detection of typhoid cases with an additional advantage of separate determination of IgM and IgG antibody, thereby aiding in identification of current infection and previous exposure so that appropriate and timely treatment could be given to the patients.

Histone deacetylases (HDACs) regulate gene expression epigenetically through synchronized removal of acetyl groups from histones required towards memory consolidation. Moreover, dysregulated epigenetic machinery during fear or extinction learning may result in altered expression of some of these genes and result in Post Traumatic Stress Disorder (PTSD). In the present study, region-specific expression of Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC2) was correlated to the acetylation of histones H3 and H4 and the resultant conditioned response, in rats undergone fear and extinction learning. The neuronal activation, histone acetylation at H3/H4 and expression of HDAC1/HDAC2 in centrolateral amygdala (CeL) and centromedial amygdala (CeM) of central Amygdala (CeA) and prelimbic (PL) and infralimbic (IL) of Prefrontal cortex (PFC) were found to be associated in a differential manner following fear and extinction learning. Moreover in CeM, the main output of the fear circuitry, the level of HDAC1 was down-regulated following conditioning and up-regulated following extinction as opposed to which HDAC2 was down-regulated in CeM following conditioning but not following extinction. Furthermore, in CeL the HDAC1 was upregulated and HDAC2 was downregulated following conditioning and extinction. This has important implications in speculating of the role of HDACs in fear memory consolidation and its extinction.

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses

Lead (Pb) is ubiquitous, naturally occurring heavy metal that has a neurotoxic effect on the CNS and causes a range of health problems in humans, including cognitive impairment. Its toxicity remains a worldwide health issue, especially in developing countries. In this study, we tend to investigate the relationship between Pb poisoning and sociodemographic status, intellectual and neurobehavioral capabilities of children.The background characteristics of the research subjects were collected via questionnaire. The study involved 43 children, aged from 4 to 12 years. Blood lead (BL) levels were analysed by using anodic stripping voltammeter (ASV). Intelligence quotient (IQ) was another parameter that was assessed via using the Goodenough draw-A-person test in Pb exposed as well as control children. Although sociodemographic information was obtained in a questionnaire pattern from the parents.The mean of BL level was 19.93 ± 9.22 μg/dL. BL levels were considerably higher with low social status (p 0.05), maternal employment (p 0.001) and the maximum time spent outdoors (p 0.001). Source of water, age of subjects, type of house and kohl used by children was observed to be significantly correlated with BL levels i.e. (p 0.05). IQ levels were decreased in a concentration dependent manner (p 0.01). Negative correlations were found between BL levels and IQ levels (r = -0.963,0.01). Girls were found to be higher IQ level than boys (p 0.05). Moreover, higher socioeconomic status had a higher IQ level (p 0.01) as compared to low.BL levels were significantly associated with IQ levels. Sociodemographic characteristic was also found to be one of the risk factors that influenced the BL levels of children. Our investigations have demonstrated that the exposure of Pb severely affected the learning with memory, and the intelligence quotient of children, that is found inversely proportional in respect to BL levels.

Lead (Pb) is found in almost all phases in environment and biological systems. Pb stimulated oxidative stress is a state that involves the generation of free radicals beyond the permissible limits, which can deplete the antioxidant reserves and can result in oxidative stress, thus hampering the ability of the biological system to reverse the result. Exposure of rats to Pb (25 mg/kg body weight) for 8 weeks caused an increase in Pb levels in blood and brain. Activity of delta-aminolevulinic acid dehydratase (δ-ALAD) and antioxidant enzymes such as Superoxide dismutase (SOD) and Catalase (CAT) decreased in the blood of Pb-treated group with a concomitant increase in the level of lipid peroxidation (LPO) and no significant change in the level of reduced glutathione (GSH) level was found. Interestingly, co-treatment of Pb-treated rats with curcumin (30 mg/kg body weight) and quercetin (30 mg/kg body weight) for 8 weeks caused a significant decrease in Pb levels of blood and all brain regions versus those treated with Pb alone. A significant improvement in levels of MDA, δ-ALAD, SOD and CAT activities was observed in rats simultaneously treated with curcumin or Quercetin or both with lead. Therefore, the ameliorative impact of curcumin and Quercetin might be due to their antioxidant property hence were able to counter the oxidative stress generated by Pb. These results suggest that combination of curcumin and Quercetin could be utilized as a possible supplement with the relevant therapeutics in the suitable management of Pb toxicity

Lipids are a key component of membranes and act as bioactive signaling molecules in biological systems. Over the years, lipids have gained much significance as their roles are being highlighted through various studies. The structural and functional diversity of lipid structure allows great variety to roles that these lipids can play in cellular organisms. With an increase of research interests in area related to lipids, much emphasis has been put toward the manner in which these can be analyzed. Recent developments in mass spectrometry-based platforms have allowed us to generate global lipid maps at the cellular level and elucidate the molecular complexity of lipid structures in detail. In this chapter we discuss some aspects of lipid classification, their structure and functions, and mass spectrometry-based lipidomics approach used for determination of lipid compositions.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19. Communicated by Ramaswamy H. Sarma, Graphical Representation of Proposed Study

Lead (Pb) is a worldwide concern due to its persistent property in the environment. However, due to diminutive evidence and elusiveness, the impact of lead exposure on the biochemical and haematological parameter in school-age children is not well established.This study primarily aimed to investigate blood lead (BL) in children and its association with haematological and biochemical parameter.A total of 43 children (4-12 years) were recruited in each control and study group. Furthermore, the study group were subdivided into two groups (group A (10 μg/dl) and group B (10 μg/dl)). BL level, haematological parameter including haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, total leukocytes count, neutrophils, lymphocytes, monocytes, mean corpuscular volume, red cell distribution width, eosinophil's, platelets in the whole blood and biochemical parameter such as liver function test (total bilirubin, alkaline phosphatase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total protein, albumin) and kidney function test (sodium, potassium, blood urea nitrogen, creatinine) in serum were measured using anodic stripping voltammeter (ASV), Cell-Dyn Ruby Haematology analyser, Beckman coulter Unicel Dxc 800 Synchron Clinical analyser respectively.The arithmetical mean of BL level was 19.93 ± 9.22 μg/dl (median: 17.5 μg/dl; range 9.1-37.4 μg/dl). Only 21 % children had BL levels10 μg/dl and there were 79 % children with BL levels10 μg/dl. Blood mean corpuscular haemoglobin concentration, Neutrophils, Monocytes were significantly higher between the control and study group. Additionally, haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, Lymphocytes and mean corpuscular volume intensities were significantly lower in10 μg/dl group whereas total leukocytes count, neutrophils, monocytes, red cell distribution width, eosinophil's, platelets levels were statistically higher (p0.001). Serum alkaline phosphatase, serum glutamic-oxaloacetic transaminase, total protein, were higher (p0.05) and sodium, albumin were significantly lower in the study group. The mean value of sodium, potassium, total bilirubin, alkaline phosphatase, serum glutamic-pyruvic transaminase, total protein and blood urea nitrogen, creatinine in two groups (10 μg/dl and10 μg/dl) was not significantly different. Serum glutamic-oxaloacetic transaminase level was significantly higher (p = 0.015) while albumin levels were significantly lower (p = 0.034) in10 μg/dl group. A statistically significant correlation of BL levels with all haematological parameters was also observed. Creatinine is positively and albumin was negatively correlated with BL levels.The outcomes specify that high BL levels were significantly associated with higher haematological and biochemical indices in exposed children. However, lead like noxious metals severely affected the haematological, kidney and liver health of children.

Japanese encephalitis (JE) is neurological infection which is caused by Japanese encephalitis virus (JEV), a flavivirus, and is closely related to St. Louis encephalitis and West Nile encephalitis. It is predominant in rural areas of Asia, which spread through bites of culicine mosquitoes, most often Culex tritaeniorhynchus. JE has broad range of manifestations. It can range from subtle changes in behavior to serious problems, including blindness, ataxia, weakness, and movement disorders.Japanese encephalitis virus is endemic in 24 countries in Southeast Asia and Western Pacific regions with more than 3 billion people at risk of infection. JE is the main cause of viral encephalitis in people in many countries of Asia amounting almost 68,000 clinical cases per year. Children are at greatest risk, with adults in endemic areas having protective immunity as a consequence of childhood infection. This disease is of particular importance in Gorakhpur, eastern belt of UP, the state with the largest population in India, where a large number of children have been dying in the past several years with alarming frequency since 1978.

Background: Hepatitis C virus (HCV) causes acute as well as chronic hepatitis such as cirrhosis of liver and hepatocellular carcinoma. The virus is mainly transmitted through blood and blood products. Hence, in order to provide safe blood supply testing of each blood unit for markers of HCV has been made mandatory. The infection is detected by the presence of anti-HCV antibody in the patient’s serum. The objective of the present study was to determine the prevalence of anti-HCV antibodies among indoor patients and blood donors. Methods: A hospital based cross-sectional study was done from January to June 2016. A total of 1991 subjects comprising of 1649 indoor patients and 342 blood donors were included in the study whose blood samples were screened for presence of anti-Hepatitis C antibody using rapid HCV TRI-DOT and HCV Microlisa. Results: Out of 1649 indoor patients tested, 39 were found to be reactive, and out of 342 blood donors tested, 4 were found to be reactive, hence, the prevalence of anti-HCV antibody was found to be 2.4% among indoor patients and 1.2% among blood donors. The seroprevalence of anti-HCV antibody was found to be more among replacement donors (1.2%) as compared to voluntary donors (1.1%). Conclusions: As blood transfusion is an important mode of transmission of HCV, hence, prevention in the form of proper screening of every unit of blood prior to transfusion is mandatory. As voluntary donors are relatively safe, this should be encouraged by organizing frequent blood donation camps.

Background: Enteric fever is a major public health problem with significant morbidity and mortality in developing countries. Although, isolation of causative organism from blood is the standard laboratory method, but due to frequent use of self-medication by patients, and its long turnaround time, it is seldom used, and enteric fever is usually diagnosed by using serological methods. Widal tube agglutination test is the standard serological test used, which is now a days replaced by slide agglutination test due to its convenience and rapidity. The present study was done to comparatively evaluate the slide agglutination and Widal tube agglutination test in detecting enteric fever. Methods: A hospital based cross-sectional study was done from January to June 2016. A total of 117 patients with clinical presentation suggestive of enteric fever were included in the study whose venous blood was collected and serum was tested by both slide agglutination and Widal tube agglutination test. Results: Out of 117 patients, slide agglutination test showed positive results in 39 (33.3%) samples, whereas, Widal tube agglutination test showed positive results in 23 (19.7%) samples only. The slide test had a sensitivity of 91.3%, specificity of 80.9%, positive predictive value of 53.8% and negative predictive value of 97.4% as compared to Widal tube agglutination test. Conclusions: Due to high false positivity shown by slide test, it is suggested that serological diagnosis should not be made solely on the basis of slide test rather its results should be confirmed by using Widal tube agglutination test.

Dengue fever, a very old disease, has re-emerged during past 20 years besides, an expanded geographic distribution of both the viruses and the mosquito vectors. With increased epidemic activity, the development of hyperendemicity (the co-circulation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease was the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in 21st century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. Based on the data of National Vector Borne Disease Control Programme (NVBDCP), the number of cases reported in 2016 in India was about 1,11,880 for dengue with 227 deaths1. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. Major challenges for public health officials in all tropical areas of the world is to develop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.

Medicinal plants having immunomodulatory properties provide an alterna-tive potential to conventional chemotherapy for a variety of diseases espe-cially in relation to host defense mechanism. Curcumin one of major curcu-minoids of Curcuma longa, reportedly possess several pharmacological prop-erties including anti-inflammatory, anti-cancer, immunomodulatory activi-ties. Curcumin blocks inflammatory enzymes cyclooxygenase (COX), lipooxy-genase (LOX), matrix metalloproteinase (MMP). Curcumin suppresses the proliferation of a wide variety of tumour cells, including breast carcinoma, colon carcinoma, and renal cell carcinoma through cell cycle arrest. It in-duced apoptosis by downregulation of antiapoptotic protein (Bcl-2 and Bcl-xL). Curcumin modulates immune system by suppressing T-cells, proliferating number of B-cells and reducing proliferation of immature B-cell lymphoma cells. Curcumin treatment inhibited the production of cytokines (IL-8, MIP-1α, MCP-1, IL-1β, TNF-α) and dimerisation of TLR’s. Immunoregulatory activi-ty of curcumin is by inhibiting phosphorylation of IKKβ which ultimately leads to suppression of NF-κB (transcriptional activator protein). This activity of curcumin has renewed scientific interest in its potential to prevent and treat the diseases such as arthritis, allergy, asthma & cancer.

Capsaicin, an ingredient of red chili pepper, has been shown to suppress the growth of pancreatic cancer. Its role and mechanism of action is currently under extensive investigation. Capsaicin has demonstrated the ability to inhibit the proliferation of pancreatic cancer cells through reactive oxygen species (ROS). The relationship between ROS, antioxidants, and possible pathways for inhibition of pancreatic cancer mediated by capsaicin is discussed in this chapter.

Calcium ions play an importantrole in various physiological processes such as nerve impulse transmission, muscle contraction, hormone action, blood clotting. They ions act as an intracellular second messenger, relaying information within cells to regulate their activity. To understand the mechanism of hepatotoxicity of t-BHP, studies were carried out using freshly isolated rat hepatocytes. The effect of t-BHP on Ca(2+) accumulation and Ca(2+) uptake by rat hepatocytes was monitored using 45Ca(2+). It caused decrease in 15% accumulation of 45Ca(2+) in comparison to the control group. t-BHP also significantly decreased the Ca(2+) ATPase activity in isolated hepatocytes .This decrease in Ca(2+) ATPase activity by t-BHP was reversed 40% by naturally occurring antioxidant glutathione (GSH) and 20% by the synthetic antioxidant butylated hydroxy toluene (BHT). These results indicate that the hepatotoxic action of t-BHP involves oxidative stress as evident by the protection accorded by various antioxidants employed in the study as well as impairment of intracellular calcium homeostasis which can lead to liver cell injury.

Under in vitro conditions involving formation of active oxygen species, rat liver mitochondria were found to undergo swelling, peroxidative decomposition of lipids, and distinct disorganization of ultrasture. supplementation with free radical scavengers such as superoxide dismutase (SOD), methionine, histidine, and tryptophan accorded considerable protection to the organelle. A possible correlation between oxygen radicals, membrane integrity, and calcium functions is indicated.

t-BHP induced oxidative stress and Ca2+ function impairment in fresh hepatocytes was studied in order to understand its role in cytotoxicity. Viability of hepatocytes by the release of lactate dehydrogenase and methyl thiazoletetrazolium reduction method alongwith malondialdehyde formation indicated oxidative stress in the hepatotoxic action of t-BHP.

Tert-butyl hydroperoxide induced swelling of freshly isolated rat liver mitochondria was inhibited by butylated hydroxytoluene, butylated hydroxyanisole and alpha-tocopherol by acting at the initial phase. EDTA was more effective than EGTA in reducing the initial swelling and so were desferal and bipyrridyl. Spermine, an allosteric activator of calcium uptake, enhanced swelling whereas lanthanum and ruthenium red, the Ca2+ uniport blockers, reduced it. Inhibition of phospholipase A2 by dibucaine and Ca2+ activated proteases by antipain and leupeptin also reduced t-BHP induced swelling. The data indicate that peroxidative mitochondrial swelling involves an iron mediated initial rapid phase and a subsequent calcium dependent propagation phase.

In order to understand any involvement of altered calcium functions in peroxidative membrane damage, the effect of a few chemicals, known to modify specific biological responses involving calcium related functions on mitochondrial swelling in vitro was studied. Histamine caused swelling, whereas antihistamines reduced calcium induced swelling. Anti-inflammatory agents aspirin and indomethacin did not affect the initial rapid phase of swelling but reduced the swelling during the later phase. The uncouplers of oxidative phosphorylation and electron transport chain blockers such as dinitrophenol (DNP), antimycin-A and rotenone reduced swelling and the respiratory inhibitors KCN and sodium azide completely abolished it. Trifluoperazine, an anti-calmodulin agent did not influence the initial phase of calcium induced swelling but in the subsequent phase swelling was reduced. c-AMP as well as calcium ionophores, calcimycin and lasalocid acid, potentiated swelling. Thus agents capable of modulating calcium functions could influence the in vitro swelling of mitochondria.

Incubation of freshly isolated rat liver mitochondria in the presence of oxygen free radical generating hypoxanthine-xanthine oxidase system led to swelling of mitochondria as measured by the change in optical density, which was reversed by the addition of superoxide dismutase. O2- in the presence of CaCl2 enhanced the peroxidative decomposition of mitochondrial membrane lipids along with swelling of the organelle. Free radical generation led to enhancement of monoamine oxidase activity while glutathione peroxidase and cytochrome c oxidase were inhibited. Tert-butyl hydroperoxide (t-BHP) caused mitochondrial swelling through oxidative stress. Incorporation of ruthenium red, which is a Ca2+ transport blocker, during assay abolished peroxidative membrane damage and swelling. Dithiothreitol (DTT) accorded protection against t-BHP induced mitochondrial swelling. The above in vitro data suggest a possible interrelationship of active oxygen species, membrane damage and calcium dynamics.

A computational method for lateral-directional aerdynamics of fighter configurations is developed. The leading-edge vortices are represented by free vortex filaments which are adjusted iteratively to satisfy the forcefree condition. The forebody vortex separation, both symmetrical and asymmetrical, is calculated with a slender body theory. Effect of boundary layer separation on lifting surfaces is accounted for by using the effective sectional angles of attack. The latter are obtained iteratively by matching the nonlinear sectional lift with the computed results based on a lifting-surface theory. Results for several fighter configurations are employed for comparison with available data. It is shown that the present method produces reasonable results in predicting sideslip derivatives, while roll- and yaw-rate derivatives do not compare very well with forced-oscillation test data at high angles of attack.