Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

Occurrence, speciation, and controls on arsenic mobilization in the alluvial aquifer system of the Ghaghara basin, India.

High concentrations of arsenic (As) in groundwater are among the long-standing environmental problems on the planet. Due to adverse impacts on the human and aquatic system, characterization and quantification of individual inorganic As species are crucial in understanding the occurrence, environmental fate, behaviour, and toxicity in natural waters. This study presents As concentration and its speciation As(III) and As(V) data, including the interrelationship with other major and trace aqueous solutes from parts of the Ghaghara basin, India. More than half (57%) of the groundwater samples exhibited elevated As concentrations (> 10 µg/L), whereas 67.4% of samples have higher As(III) values relative to As(V), signifying a potential risk of As(III) toxicity. The elevated concentration of As was associated with higher Fe, Mn, and HCO3-, especially in samples from shallow well depth. PHREEQC modeling demonstrates the presence of mineral phases such as hematite, goethite, rhodochrosite, etc. Therefore, it is inferred that the release of As from sediment particles into pore water via microbially mediated Fe/Mn oxyhydroxides, and As(V) reduction processes mainly control high As concentrations. The heavy metal pollution indices (HPI) and (HEI) values revealed heavy metal pollution in low-lying areas deposited by relatively younger sediments along the Ghaghara River. Large-scale agricultural practices, overexploitation of groundwater, and indiscriminate sewage disposal, in addition to geogenic factors, cannot be ruled out as potential contributors to As mobilization in the region. This study recommends conducting seasonal hydrogeochemical monitoring and investigating regional natural background levels of As, to precisely understand the controlling mechanistic pathways of As release.

Distribution, geochemical behavior, and risk assessment of arsenic in different floodplain aquifers of middle Gangetic basin, India.

The present study interprets the distribution and geochemical behavior of As in groundwaters of different regions along the floodplains of Ganga river (Varanasi, Ghazipur, Ballia), Ghaghara river (Lakhimpur Kheri, Gonda, Basti), and Rapti river (Balrampur, Shrawasti) in the middle Gangetic basin, India for risk assessment (non-carcinogenic and carcinogenic). The concentration of As in groundwaters of these floodplains ranged from 0.12 to 348 µg/L (mean 24 µg/L), with around ~ 37% of groundwater samples exceeding the WHO limit of 10 µg/L in drinking water. Highest As concentration (348 µg/L) was recorded in groundwater samples from Ballia (Ganga Floodplains), where 50% of the samples had As > 10 µg/L in groundwater. In the study area, a relatively higher mean concentration was recorded in deep wells (28.5 µg/L) compared to shallow wells (20 µg/L). Most of the high As-groundwaters were associated with the high Fe, bicarbonate and low nitrate and sulfate concentrations indicating the release of As via reductive dissolution of Fe oxyhydroxides. The saturation index values of the Fe minerals such as goethite, hematite, ferrihydrite, and siderite showed the oversaturation to near equilibrium in groundwater, suggesting that these mineral phases may act as source/sink of As in the aquifers of the study area. The health risk assessment results revealed that a large number of people in the study area were prone to carcinogenic and non-carcinogenic health risks due to daily consumption of As-polluted groundwater. The highest risks were estimated for the aquifers of Ganga floodplains, as indicated by their mean HQ (41.47) and CR (0.0142) values.

FLAIR MRI biomarkers of the normal appearing brain matter are related to cognition.

A novel biomarker panel was proposed to quantify macro and microstructural biomarkers from the normal-appearing brain matter (NABM) in multicentre fluid-attenuation inversion recovery (FLAIR) MRI. The NABM is composed of the white and gray matter regions of the brain, with the lesions and cerebrospinal fluid removed. The primary hypothesis was that NABM biomarkers from FLAIR MRI are related to cognitive outcome as determined by MoCA score. There were three groups of features designed for this task based on 1) texture: microstructural integrity (MII), macrostructural damage (MAD), microstructural damage (MID), 2) intensity: median, skewness, kurtosis and 3) volume: NABM to ICV volume ratio. Biomarkers were extracted from over 1400 imaging volumes from more than 87 centres and unadjusted ANOVA analysis revealed significant differences in means of the MII, MAD, and NABM volume biomarkers across all cognitive groups. In an adjusted ANCOVA model, a significant relationship between MoCA categories was found that was dependent on subject age for MII, MAD, intensity, kurtosis and NABM volume biomarkers. These results demonstrate that structural brain changes in the NABM are related to cognitive outcome (with different relationships depending on the age of the subjects). Therefore these biomarkers have high potential for clinical translation. As a secondary hypothesis, we investigated whether texture features from FLAIR MRI can quantify microstructural changes related to how "structured" or "damaged" the tissue is. Based on correlation analysis with diffusion weighted MRI (dMRI), it was shown that FLAIR MRI texture biomarkers (MII and MAD) had strong correlations to mean diffusivity (MD) which is related to tissue degeneration in the GM and WM regions. As FLAIR MRI is routinely collected for clinical neurological examinations, novel biomarkers from FLAIR MRI could be used to supplement current clinical biomarkers and for monitoring disease progression. Biomarkers could also be used to stratify patients into homogeneous disease subgroups for clinical trials, or to learn more about mechanistic development of dementia disease.

An in-silico analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α.

Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPß1, leading to the prevention of nuclear localization signal (NLS) recognition. Therefore, the current study seeks to employ molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) analysis and molecular dynamics simulation studies for decrypting the binding mode, key interacting residues as well as mechanistic insights on IVM interaction with 15 potential drug targets associated with COVID-19 as well as IMPα. Among all COVID-19 targets, the non-structural protein 9 (Nsp9) exhibited the strongest affinity to IVM showing -5.30 kcal/mol and -84.85 kcal/mol binding energies estimated by AutoDock Vina and MM-GBSA, respectively. However, moderate affinity was accounted for IMPα amounting -6.9 kcal/mol and -66.04 kcal/mol. Stability of the protein-ligand complexes of Nsp9-IVM and IMPα-IVM was ascertained by 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of protein in complex with docked IVM exhibited stable root mean square deviation while root mean square fluctuations were also found to be consistent. In silico exploration of the potential targets and their interaction profile with IVM can assist experimental studies as well as designing of COVID-19 drugs. Communicated by Ramaswamy H. Sarma.

Antidiabetic, antioxidant, molecular docking and HPTLC analysis of miquelianin isolated from Euphorbia schimperi C. Presl.

The present study demonstrates the miquelianin or quercetin 3-O-glucuronide (compound 1) isolated from aerial parts of Euphorbia schimperi exhibited significant results for antioxidant and antidiabetic potential. The compound 1 along with kaempferol 3-O-glucuronide (compound 2) and quercetin 3-O-rhamnoside (compound 3) isolated from the same source were quantified by validated HPTLC method. Antioxidant activity was determined by chemical means in terms of ABTS radical cation and DPPH radical scavenging activity. Compound 1 showed significant scavenging activity in both ABTS and DPPH assays as compared to standard BHA. In ABTS method IC50 values of compound 1 and standard BHA is found to be 58.90 ±â€¯3.40 µg/mL and 28.70 ±â€¯5.20 µg/mL respectively while in DPPH assay IC50 values of Compound 1 and standard BHA is 47.20 ±â€¯4.90 µg/mL and 34.50 ±â€¯6.20 µg/mL respectively. Antidiabetic effect was studied through α-amylase and α-glucosidase inhibitory activity. The mechanistic approach through molecular modelling also support the strong binding sites of compound 1 which showed significant α-amylase and α-glucosidase inhibitory activities with IC50 values 128.34 ±â€¯12.30 and 89.20 ±â€¯9.20 µg/mL respectively as compared to acarbose 64.20 ±â€¯5.60 and 52.40 ±â€¯4.60 µg/mL respectively. The results of validated RP-HPTLC analyses revealed the concentration of compound 1 found to be 16.39 µg/mg and for compound 2 and compound 3 as 3.92 and 14.98 µg/mg of dried extract, respectively.

Depth extraction with offset pixels.

Numerous depth extraction techniques have been proposed in the past. However, the utility of these techniques is limited as they typically require multiple imaging units, bulky platforms for computation, cannot achieve high speed and are computationally expensive. To counter the above challenges, a sensor with Offset Pixel Apertures (OPA) has been recently proposed. However, a working system for depth extraction with the OPA sensor has not been discussed. In this paper, we propose the first such system for depth extraction using the OPA sensor. We also propose a dedicated hardware implementation for the proposed system, named as the Depth Map Processor (DMP). The DMP can provide depth at 30 frames per second at 1920 × 1080 resolution with 31 disparity levels. Furthermore, the proposed DMP has low power consumption as for the aforementioned speed and resolution it only requires 290.76 mW. The proposed system makes it an ideal choice for depth extraction systems in constrained environments.

Phylogenetic and genetic variation analyses of porcine circovirus type 2 isolated from China.

Porcine circovirus type 2 (PCV2) is a causative agent of PCV2-associated disease, which is a growing problem in the swine industry worldwide. High nucleotide substitution occurs in the capsid (Cap) gene of PCV2, which allows the continuous evolution and the emergence of novel PCV2 strains. In this study, we sequenced 24 Chinese PCV2 strains collected from healthy and diseased pigs between 2013 and 2015. Analyses of the genome, Cap and phylogeny classified the 24 Chinese PCV2 strains as PCV-2a (four of 24), PCV-2b (five of 24) and PCV-2d (15 of 24). All strains shared 89.5%-100% and 87.2%-100% identities with the nucleotide and amino acid (aa) sequences of Cap, respectively. Selection pressure analysis showed that five sites at the epitope regions in Cap were under positive selection. Further analysis by Jameson-Wolf antigenic index indicated that aa substitutions occurring at the epitope regions contributed to the antigenic alterations of the different PCV2 strains. High genetic variation and genotype shift to PCV2d occurred in recent years, and different genotypes coexisted in Chinese pig herds. The data provide evidence for the increased genetic diversity and insights into the molecular epidemiology of PCV2.

The novel role of ß-aescin in attenuating CCl4-induced hepatotoxicity in rats.

CONTEXT: ß-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties. OBJECTIVE: The present study investigated the hepatoprotective effect and underlying mechanisms of ß-aescin in CCl4-induced liver damage. MATERIALS AND METHODS: Thirty-five Wistar rats were divided into six groups: normal control, CCl4 control, silymarin (50 mg/kg, p.o) and ß-aescin (0.9, 1.8 and 3.6 mg/kg, i.p.) treatment for 14 d. CCl4 (1 mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-ß1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out. RESULTS: ß-Aescin (3.6 mg/kg) markedly decreased CCl4-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259 IU/L, respectively), total bilirubin (0.41 versus 1.35 mg/dL), TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL) and increased CCl4-induced decreased GSH levels (0.095 versus 0.048 µmol/mg protein). ß-Aescin (3.6 mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL), TGF-ß1 (92.28 versus 152.1 pg/mL), collagen content (110.75 versus 301.74 µmol/100 mg tissue) and TNF-α (92.82 versus 170.56 pg/mL) when compared with CCl4 control. DISCUSSION AND CONCLUSION: The findings suggest that ß-aescin has a protective effect on CCl4-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.

Seroprevalence of Toxoplasma gondii in South Asian countries.

Toxoplasmosis, a cosmopolitan zoonosis, is caused by an apicomplexan, obligate, intracellular protozoan parasite, Toxoplasma gondii. Nearly all animals, including humans, are at risk owing to its broad geographical distribution. The authors searched published data related to T. gondii in databases, including Google Scholar, PubMed and Science Direct for South Asian countries, and retrieved a total of 113 articles fulfilling the criterion of seroprevalence investigation. Toxoplasma gondii infection in livestock and humans was investigated using various serological tests. In these studies, a total of 14,431 samples from domestic animals and 53,899 samples from humans were screened for anti-T. gondii antibodies in all South Asian countries. Among the animals, cattle (n = 1,981), goats (n = 3,285), buffaloes (n = 1,695), sheep (n = 1,747), cats (n = 1,480), camels (n = 435), elephants (n = 45), pigs (n = 920), dogs (n = 1,604) and poultry (n = 1,206) were tested. This comprehensive review will be useful to biologists, public health workers, physicians and veterinarians and provides a better understanding of the distribution of T. gondii in this region. Furthermore, this knowledge will support efforts to find and apply effective prevention measures to better manage this zoonosis in South Asian countries.

La toxoplasmose est une maladie cosmopolite causée par Toxoplasma gondii, un protozoaire unicellulaire obligatoire appartenant au phylum des Apicomplexa. Du fait de sa distribution géographique, pratiquement toutes les espèces animales sont exposées, ainsi que l'homme. Les auteurs ont fait une recherche dans plusieurs bases de données, dont Google Scholar, PubMed et Science Direct, sur les articles consacrés à T. gondii dans les pays d'Asie du Sud, qui a permis d'extraire un total de 113 articles présentant toutes les caractéristiques d'une enquête sérologique. L'infection par Toxoplasma gondii chez l'homme et chez les animaux d'élevage a fait l'objet de plusieurs enquêtes recourant à divers tests sérologiques. Ces études font état d'un total de 14 431 échantillons prélevés d'animaux domestiques et de 53 899 échantillons prélevés chez l'homme, qui ont été soumis à une épreuve de détection d'anticorps dirigés contre T. gondii dans les pays d'Asie du Sud. Les études ont couvert les espèces suivantes : bovins (n = 1 981), chèvres (n = 3 285), buffles (n = 1 695), moutons (n = 1 747), chats (n = 1 480), chameaux (n = 435), éléphants (n = 45), porcs (n = 920), chiens (n = 1 604) et volailles (n = 1 206). Ce panorama exhaustif sera utile aux biologistes, aux intervenants en santé publique, aux médecins et aux vétérinaires et permettra de mieux appréhender la distribution de T. gondii dans la région. Ces connaissances contribueront à concevoir et à appliquer des mesures de prévention efficaces afin de mieux gérer cette zoonose dans les pays d'Asie du Sud.

La toxoplasmosis es una zoonosis cosmopolita causada por un protozoo, parásito intracelular obligado, del grupo de los apicomplejos: Toxoplasma gondii. Por su amplia distribución geográfica, constituye una amenaza para casi todos los animales, incluido el ser humano. Tras indagar en bases de datos de publicaciones (Google Scholar, PubMed y Science Direct) en busca de información relacionada con la presencia de T. gondii en los países del meridión asiático, los autores encontraron un total de 113 artículos que cumplían el criterio de dar cuenta de investigaciones sobre la seroprevalencia. Para estudiar la infección por Toxoplasma gondii en el ganado y el ser humano se habían empleado diversas pruebas serológicas. En el conjunto de esos estudios, que cubrían todos los países de Asia meridional, se habían analizado un total de 14.431 muestras de animales domésticos y 53.899 muestras humanas para detectar anticuerpos contra T. gondii. Los animales analizados eran: ganado vacuno (n = 1.981), cabras (n = 3.285), búfalos (n = 1.695), ovejas (n = 1.747), gatos (n = 1.480), camellos (n = 435), elefantes (n = 45), cerdos (n = 920), perros (n = 1.604) y aves de corral (n = 1.206). Este repaso general, que resultará útil a biólogos, agentes de salud pública, médicos y veterinarios, permite conocer mejor la distribución de T. gondii en la región, lo que además será de ayuda a la hora de determinar y aplicar medidas eficaces de prevención con objeto de controlar más eficazmente esta zoonosis en los países de Asia meridional.

Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy.

Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core. Three different sizes of magnetic nanoparticles (10, 22 and 30nm) and liposomes (40, 70 and 110nm) were used in this study. Magnetite single domain nanoparticles forming the magnetic core were superparamagnetic but liposomes expressed slight coercivity and hysteresis due to the clustering of nanoparticles in the core. This enhanced the heating efficiency (specific power loss) of the liposomes under an AC field (375kHz, 170Oe). Cell viability and toxicity were studied on HeLa cells using MTT assay and proteomic analysis. Confocal and fluorescence microscopy were used to study the photosensitizer's profile and cells response to combined therapy. It revealed that combined therapy almost completely eliminated the cancer cells as opposed to the separate treatments. Magnetic hyperthermia and photodynamic therapies were almost equally effective whereas chemotherapy showed the least effect.

Placenta accreta and anesthesia: A multidisciplinary approach.

Placenta accreta (an abnormally adherent placenta) is one of the two leading causes of peripartum hemorrhage and the most common indication for peripartum hysterectomy. Placenta accreta may be associated with significant maternal hemorrhage at delivery owing to the incomplete placental separation. When placenta accreta is diagnosed before delivery, a multidisciplinary approach may improve patient outcome.

Calendula officinalis ameliorates l-arginine-induced acute necrotizing pancreatitis in rats.

CONTEXT: Calendula officinalis L. (Asteraceae) has been traditionally used in treating inflammation of internal organs, gastrointestinal tract ulcers and wound healing. OBJECTIVE: The present study investigates the effect of ethanol extract (95%) of Calendula officinalis flowers in l-arginine induced acute necrotizing pancreatitis in rats. MATERIALS AND METHODS: Rats were divided into four groups: normal control, l-arginine control, Calendula officinalis extract (COE) treated and melatonin treated (positive control), which were further divided into subgroups (24 h, day 3 and 14) according to time points. Two injections of l-arginine 2 g/kg i.p. at 1 h intervals were administered in l-arginine control, COE and melatonin-treated groups to produce acute necrotizing pancreatitis. Biochemical parameters [serum amylase, lipase, pancreatic amylase, nucleic acid content, total proteins, transforming growth factor-ß1 (TGF-ß1), collagen content, lipid peroxidation, reduced glutathione and nitrite/nitrate] and histopathological studies were carried out. RESULTS: COE treatment (400 mg/kg p.o.) was found to be beneficial. This was evidenced by significantly lowered histopathological scores (2 at day 14). Nucleic acid content (DNA 21.1 and RNA 5.44 mg/g pancreas), total proteins (0.66 mg/mL pancreas) and pancreatic amylase (1031.3 100 SU/g pancreas) were significantly improved. Marked reduction in pancreatic oxidative and nitrosative stress; collagen (122 µmoles/100 mg pancreas) and TGF-ß1 (118.56 pg/mL) levels were noted. Results obtained were comparable to those of positive control. DISCUSSION AND CONCLUSION: The beneficial effect of COE may be attributed to its antioxidant, antinitrosative and antifibrotic actions. Hence, the study concludes that COE promotes spontaneous repair and regeneration of the pancreas.

Hepatoprotective effect of trans-Chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis.

The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4 and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-ß1, collagen content), hepatic inflammation (TNF-α), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti-oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent.

Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-ß1 (TGF-ß1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-ß1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

Anesthetic consideration in dystrophic epidermolysis bullosa.

Epidermolysis bullosa is a group of inherited rare skin disease, characterized by bullae formation in the skin or mucous membranes. The fundamental abnormality is collagen degeneration leads to splitting of various epidermal layers. Dystrophic epidermolysis bullosa (DEB) is one of the major forms of epidermolysis bullosa. These patients often admitted to the hospital for corrective surgeries, change of dressing, contracture release, and skin grafting. Anesthetic management of these cases is always a challenge. We are reporting a case of 5-year-old boy diagnosed as a case of DEB scheduled for upper lip contracture release, skin grafting and debridement of nonhealing scars under anesthesia. In this case, we have focused mainly on the anesthetic management, preparation of the monitoring, transportation, difficulties in establishing the venous accesses, and airway management.

A comparative study on the cardioprotective potential of atorvastatin and simvastatin in hyperhomocysteinemic rat hearts.

The present study has been deliberated in order to compare the cardioprotective potential of 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, Atorvastatin and Simvastatin in hyperhomocysteinemic rat hearts. L-methionine (1.7 g/kg/day orally) was administered to rats for 4 weeks to produce experimental hyperhomocysteinemia (Hhcy). Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. The extent of myocardial damage was assessed in terms of myocardial infarct size using triphenyltetrazolium chloride (TTC) staining, and release of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent; whereas the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury in normal and hyperhomocysteinemic rat hearts, assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Treatment with Atorvatstain (50 µM) and Simvastatin (10 µM) afforded cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent and oxidative stress. It may be concluded that reductions in the high degree of oxidative stress may be responsible for the observed cardioprotective potential of Atorva-and Simvastatin, and both statins can be used interchangeably to afford cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts.

Protective role of fibrates in cardiac ischemia/reperfusion.

Prevention of myocardial injury has been considered as the most important therapeutic challenge of today. Fibrates, the agonists of the peroxisome proliferator-activated receptor (PPAR)-a receptor, have been regarded as potent therapeutic agents in this context. Hence, the present study has been designed to investigate the effect of fibrates, i.e., Clofibrate and Fenofibrate, the potent agonists PPAR-a, on ischemia-reperfusion (I/R)-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 minutes followed by reperfusion for 120 minutes. Myocardial infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent have been conducted to assess the degree of cardiac injury. Moreover, the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione. Clofibrate and Fenofibrate showed cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH, and CK levels in coronary effluent along with reduction in I/R-induced oxidative stress. It may be concluded that the observed cardioprotective potential of Clofibrate and Fenofibrate against I/R-induced myocardial injury was due to the reductions in infarct size and oxidative stress.

Cardioprotective potential of simvastatin in the hyperhomocysteinemic rat heart.

The present study investigated the probable role of simvastatin, 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, in abrogated cardioprotection in hyperhomocysteinemic (Hhcy) rat hearts. Isolated Langendorff's perfused normal and Hhcy rat hearts were subjected to 30-min global ischemia (I) followed by 120-min reperfusion (R). Assessment of myocardial damage was done by measuring infarct size and analyzing the release of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in coronary effluent. In addition, the oxidative stress in the heart was assessed by measuring lipid peroxidation and superoxide anion generation. I/R produced myocardial injury in normal and Hhcy rat hearts by increasing myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Hhcy rat hearts showed enhanced myocardial injury and high oxidative stress as compared to normal hearts. Treatment with Simvastatin (10 µMol) afforded cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent and oxidative stress. The reductions in the high degree of oxidative stress may be responsible for the observed cardioprotection afforded by simvastatin against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts.

Clinical indications for Gallium-68 positron emission tomography imaging.

BACKGROUND: (68)Ga-PET imaging is showing slow but steady progress when compared to (18)F-FDG PET. The advantage of in-house preparation of (68)Ga without necessity of a cyclotron, and the new generator configuration with future possibility of freeze-dried kits would make it a promising PET agent for the future. METHODS: An exhaustive literature exploration was performed using the search engines High-Wire Press, Pubmed, Embase and library databases. Recent reviews on the subject and up-to-date studies on the topic were found that described the role of (68)Ga-PET imaging. Clinical experiences, including our own are described. RESULTS: Recent resurgence in development of peptides labelled with radiometals, for diagnostic and therapeutic purposes, resulted in a new beginning for (68)Ga-PET imaging. Pre-clinical experience employing animal models and investigation of tracer kinetics/tumour uptake measurements using dynamic (68)Ga-PET have provided data regarding identification of Somatostatin receptors subtypes on many tumours. Present published experiences including our own support these and highlight current clinical utility of (68)Ga-PET imaging. (68)Ga-DOTATOC and (68)Ga-DOTANOC are the most prominent radiopharmaceuticals used nowadays. CONCLUSION: (68)Ga-PET is employed in the management of neuroendocrine tumours and neural crest tumours (phaeochromocytoma and paraganglioma) with diagnostic and therapeutic implications where it compliments present radiologic and scintigraphic procedures. Diagnosis and radiotherapy treatment planning for meningiomas in pertinent clinical setting is another potential use of (68)Ga-PET. Limited studies have shown its utility in prostate cancer but further studies are contemplated. Therefore, current experience tends to open a new horizon for the clinical utility of (68)Ga-PET imaging in future.