GABAergic implications in anxiety and related disorders.

Evidence indicates that anxiety disorders arise from an imbalance in the functioning of brain circuits that govern the modulation of emotional responses to possibly threatening stimuli. The circuits under consideration in this context include the amygdala's bottom-up activity, which signifies the existence of stimuli that may be seen as dangerous. Moreover, these circuits encompass top-down regulatory processes that originate in the prefrontal cortex, facilitating the communication of the emotional significance associated with the inputs. Diverse databases (e.g., Pubmed, ScienceDirect, Web of Science, Google Scholar) were searched for literature using a combination of different terms e.g., "anxiety", "stress", "neuroanatomy", and "neural circuits", etc. A decrease in GABAergic activity is present in both anxiety disorders and severe depression. Research on cerebral functional imaging in depressive individuals has shown reduced levels of GABA within the cortical regions. Additionally, animal studies demonstrated that a reduction in the expression of GABAA/B receptors results in a behavioral pattern resembling anxiety. The amygdala consists of inhibitory networks composed of GABAergic interneurons, responsible for modulating anxiety responses in both normal and pathological conditions. The GABAA receptor has allosteric sites (e.g., α/γ, γ/ß, and α/ß) which enable regulation of neuronal inhibition in the amygdala. These sites serve as molecular targets for anxiolytic medications such as benzodiazepine and barbiturates. Alterations in the levels of naturally occurring regulators of these allosteric sites, along with alterations to the composition of the GABAA receptor subunits, could potentially act as mechanisms via which the extent of neuronal inhibition is diminished in pathological anxiety disorders.

Magnoflorine-Loaded Chitosan Collagen Nanocapsules Ameliorate Cognitive Deficit in Scopolamine-Induced Alzheimer's Disease-like Conditions in a Rat Model by Downregulating IL-1ß, IL-6, TNF-α, and Oxidative Stress and Upregulating Brain-Derived Neurotrophic Factor and DCX Expressions.

Dementia or the loss of cognitive functioning is one of the major health issues in elderly people. Alzheimer's disease (AD) is one of the common forms of dementia. Treatment chiefly involves the use of acetylcholinesterase (AChE) inhibitors in AD. However, oxidative stress has also been found to be involved in the proliferation of the disease. Magnoflorine is one of the active compounds of Coptidis Rhizoma and has high anti-oxidative properties. Active principle-loaded nanoparticles have shown increased efficiency for neurodegenerative diseases due to their ability to cross the blood-brain barrier more easily. An in vitro study involving magnoflorine-loaded chitosan collagen nanocapsules (MF-CCNc) has shown them to possess inhibitory effects against oxidative stress and to some extent on AChE as well. In the current study, both nootropic and anti-amnesic effects of magnoflorine and MF-CCNc on scopolamine-induced amnesia in rats were evaluated. The treatment was done intraperitoneally (i.p.) once daily for 17 consecutive days with MF-CCNc (0.25, 0.5, and 1 mg), magnoflorine (1 mg), and donepezil (1 mg). To induce amnesia, hence, cognitive deficit rats were induced with scopolamine (1 mg/kg) daily for the last 9 days. Novel object recognition (NOR) and elevated plus maze (EPM) behavioral analysis were done to assess memory functioning. Hippocampal tissues were extracted to study the effect on biochemicals (AChE, MDA, SOD, and CAT), pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), and immunohistochemistry (brain-derived neurotrophic factor (BDNF) and DCX). MF-CCNc showed memory-enhancing effects in nootropic as well as chronic scopolamine-treated rats in NOR and an increase in inflexion ratio in EPM. MF-CCNc reduced the levels of AChE and MDA while increasing SOD and CAT levels in the hippocampus. MF-CCNc further lowered the levels of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. These nanocapsules further increased the expression of BDNF and DCX that are necessary for adult neurogenesis. From the research findings, it can be concluded that MF-CCNc has high anti-amnesic properties and could be a promising candidate for the treatment of AD.

Comparative Clinicopathological Evaluation of the Ocular Surface in Newly Diagnosed Patients of Hyperthyroidism and Hypothyroidism Compared to Healthy Subjects.

Introduction Thyroid eye disease is a multifactorial disorder affecting the tear film and ocular surface, which leads to dry eye. The aim of the study is to evaluate the tear function test and ocular surface changes clinically and to correlate pathologically using impression cytology in recently diagnosed cases of thyroid dysfunction, including both hyperthyroid and hypothyroid patients, and to compare the results with healthy subjects. Methods This was a cross-sectional analytical study. Thirty diagnosed patients with hyperthyroidism and hypothyroidism, each within three months, and 30 healthy age-matched controls were included. All patients and controls underwent an assessment of proptosis, palpebral fissure height (PFH), tear function test, Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear break-up time (TBUT), and impression cytology for ocular surface assessment. These parameters were compared between cases and controls. Standard statistical analysis was used. Results Mean proptosis and PFH showed no significant difference among groups (P-value = .071). The mean value of OSDI was 42.33+22.67, 41.15+16.03, and 29.33+6.84 in the hyperthyroid, hypothyroid, and controls groups, respectively; the difference being statistically significant (p=0.001). Mean TBUT was 7.13+3.28 sec, 6.38+2.46 sec, and 11.15+2.39 sec in hyperthyroidism, hypothyroidism, and controls, respectively (p=0.001). The mean value of the Schirmer tear test was 12.93+5.81 mm, 13.30+4.44 mm, and 17.55+7.35 mm in hyperthyroidism, hypothyroidism, and controls, respectively (p=0.001). Eighty percent (80%) of patients in the hyperthyroidism group had grade 2-3 squamous metaplasia as compared to 70% in hypothyroidism patients and 24.4% in controls, signifying ocular surface damage (p<0.05). Conclusions The mean PFH and proptosis did not differ between the three groups. However, increased OSDI score, decreased Schirmer's test value, decreased TBUT, and grades 2-3 squamous metaplasia in patients with thyroid dysfunction suggest the presence of dry eyes. Despite no clinically visible signs of thyroid ophthalmopathy, there is ocular surface damage right from the early stages of thyroid dysfunction, possibly attributable to the evaporative mechanism as well as ocular surface inflammation and instability of the tear film.

Resveratrol-Loaded Glutathione-Coated Collagen Nanoparticles Attenuate Acute Seizures by Inhibiting HMGB1 and TLR-4 in the Hippocampus of Mice.

Epilepsy is a relatively complicated neurological disorder that results in seizures. The use of resveratrol in treating seizures has been reported in recent studies. However, the low bioavailability of resveratrol and the difficulty of reaching the targeted location in the brain reduce its efficacy considerably. The side effects due to the higher concentration of drugs are another matter of concern. The purpose of the present study is to enhance the antiepileptic potential of resveratrol by delivering it to the brain's targeted location by encapsulating it in glutathione-coated collagen nanoparticles. The collagen nanoparticles increase the bioavailability of resveratrol, while the transport of resveratrol to its target location in the brain is facilitated by glutathione. By encapsulating resveratrol in glutathione-coated collagen nanoparticles, the concentration also substantially decreases. Resveratrol encapsulated in synthesized nanoparticles is referred to as nanoresveratrol. In the present study, nanoresveratrol effectiveness was studied through PTZ-induced seizures (PTZ-IS) and the increasing current electroshock (ICES) test. The efficacy of nanoresveratrol was further established using biochemical analysis, histopathological examinations, ELISA and real-time-PCR tests, and immunohistochemistry examination of the hippocampus of mice. Hence, this study is unique in the sense that it synthesized nanoresveratrol by using glutathione-coated collagen nanoparticles, followed by its application to treating seizures. On the basis of the study results, nanoresveratrol was found to be effective in preventing cognitive impairment in the mice and controlling epilepsy seizures to a greater extent than resveratrol. The proposed nanoformulation also reduces the concentration of resveratrol considerably. The present study results show that even 0.4 mg/kg of nanoresveratrol outperforms 40 mg/kg of resveratrol.

Nanonization of Magnoflorine-Encapsulated Novel Chitosan-Collagen Nanocapsules for Neurodegenerative Diseases: In Vitro Evaluation.

Neurodegeneration is one of the most common diseases in the aged population, characterized by the loss in the function of neuronal cells and their ultimate death. One of the common features in the progression of this type of diseases is the oxidative stress. Drugs which are currently being used have been found to show lateral side effects, which is partly due to their inefficiency to cross blood-brain barrier. Nanoencapsulation of bioactive compounds is a profound approach in this direction and has become a method of choice nowadays. This study involved the evaluation of the anti-oxidative properties of magnoflorine (MF), which is an aporphine quaternary alkaloid, and synthesis of MF-loaded chitosan-collagen nanocapsules (MF-CCNc) for its better efficacy as a potent anti-oxidant. Physiochemical characterization of the synthesized nanocapsules was done by using dynamic light scattering and transmission electron microscopy. It revealed that the synthesized nanocapsules are of small size range, as small as 12 ± 2 nm, and are more or less of spherical shape. Sustained release was shown by MF in the in vitro drug release studies. Both MF and MF-CCNc were found to have good anti-oxidant potential with IC50 < 25 µg/mL. No major cytotoxicity was shown by the synthesized nanocapsules on SH-SY5Y cells. In silico anti-acetylcholinesterase (AChE) studies were also done, and they revealed that MF can be a potent inhibitor of AChE.

Resveratrol loaded nanoparticles attenuate cognitive impairment and inflammatory markers in PTZ-induced kindled mice.

Resveratrol has been found to exert protective effects in neurological disorders, including epilepsy. However, its poor bioavailability and difficulty in reaching the brain's targeted location reduce resveratrol's efficacy substantially. The side effects due to the higher concentration of drugs are another matter of concern. The objective of the present study is to propose solutions to these issues by encapsulating resveratrol in glutathione-coated collagen nanoparticles' core. The collagen nanoparticles increase the resveratrol's bioavailability, and glutathione helps in the passage of the encapsulated resveratrol to the target location in the brain. The concentration also substantially reduces due to resveratrol's encapsulation in glutathione-coated collagen nanoparticles. The encapsulated resveratrol is termed nanoresveratrol. The effectiveness of nanoresveratrol on epilepsy seizures was evaluated through histopathological examinations, ELISA tests, and qRT-PCR tests on the hippocampus of the kindled mice. The novelty of the present study thus lies in (i) the synthesis of nanoresveratrol using glutathione-coated collagen nanoparticles and (ii) the application of synthesized nanoresveratrol in the treatment of epilepsy. The study's outcome shows that nanoresveratrol has a favorable impact in reducing cognitive impairment in kindled mice, and it is more effective in controlling epilepsy seizures than resveratrol. The p-values of all the nanoresveratrol-given groups of mice (compared with the diseased group) were substantially smaller (∼10-4 to 10-2) than the significance level (0.05), indicating that the nanoresveratrol-given groups are significantly different from the diseased group, i.e., the nanoresveratrol has a significant effect on the mice. The concentration of resveratrol also decreases substantially in the proposed nanoformulation. It was observed that even 0.4 mg/kg of nanoformulation of resveratrol is performing better than 40 mg/kg of resveratrol.

Biofabricated platinum nanoparticles: therapeutic evaluation as a potential nanodrug against breast cancer cells and drug-resistant bacteria.

Use of plant extracts for the synthesis of various metal nanoparticles has gained much importance recently because it is a simple, less hazardous, conservative and cost-effective method. In this research work, platinum nanoparticles were synthesized by treating platinum ions with the leaf extract of Psidium guajava and their structural properties were studied using various characterization techniques. The formation of platinum nanoparticles was confirmed by the disappearance of the absorbance peak at 261 nm in UV-visible spectra. The results of gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FT-IR) analysis showed functional moieties responsible for bio-reduction of metal ions and stabilization of platinum nanoparticles. The use of dynamic light scattering (DLS) imaging techniques confirmed the formation of stable monodispersed platinum nanoparticles showing a zeta potential of -23.4 mV. The morphological examination using high resolution transmission electron microscopy (HR-TEM) and Scanning electron microscopy (SEM) confirmed the formation of spherical platinum nanoparticles with an average diameter of 113.2 nm. X-ray powder diffraction (XRD) techniques showed the crystalline nature of biosynthesized platinum nanoparticles with a face-centered cubic structure. The results of energy-dispersive X-ray spectroscopy (EDAX) showed 100% platinum content by weight confirming the purity of the sample. The cytotoxic effect of biosynthesized platinum nanoparticles assessed in a breast cancer (MCF-7) cell-line by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, revealed an IC50 of 167.2 µg ml-1. The results of a wound healing assay showed that treatment with platinum nanoparticles induced an anti-migratory effect on MCF-7 cells. In the cell cycle phase distribution, treatment with platinum nanoparticles inhibited cell proliferation as determined by flow cytometry with PI staining. Significant cell cycle arrest was detected at the G0/G1 phase with a notable decrease in the distribution of cells in the S and G2/M phases. The anti-bacterial activity of bio-synthesized platinum nanoparticles was evaluated against four pathogenic bacteria i.e. B. cereus (Gram positive), P. aeruginosa (Gram negative), K. pneumonia (Gram negative) and E. coli (Gram negative). The biosynthesized platinum nanoparticles were found to show dose-dependent inhibition against pathogenic bacteria with a significant effect on Gram-negative bacteria compared to Gram-positive bacteria. This synergistic blend of green and simplistic synthesis coupled with anti-proliferative and anti-bacterial properties makes these biogenic nanoparticles suitable in nanomedicine.

Collagen Nanoparticle-Mediated Brain Silymarin Delivery: An Approach for Treating Cerebral Ischemia and Reperfusion-Induced Brain Injury.

Silymarin is a bioactive constituent isolated from milk thistle (Silybum marinum). Since its discovery, silymarin has been considered a gold standard drug in treating ailments related to the liver, resulting from alcohol consumption and viral hepatitis. This hepatoprotective nature of silymarin arises out of antioxidative and tissue-regenerating properties of silymarin. However, several recent studies have established the neuroprotective link of silymarin, too. Thus, the current investigation was aimed at exploring the neuroprotective effect of nanosilymarin (silymarin encapsulated inside collagen-based polymeric nanoparticulate drug delivery system). The study aimed at bringing out the role of nanoparticles in enhancing the therapeutic effect of silymarin against neuronal injury, originating out of oxidative-stress-related brain damages in focal cerebral ischemia. Collagen-based micellar nanoparticles were prepared and stabilized using 3-ethyl carbodiimide-hydrochloride (EDC-Hcl) and malondialdehyde (MDA) as crosslinkers. Nanoparticles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy techniques, and the size of nanoparticles was found to be around 48 nm. Male albino Wistar rats were pretreated with three different doses of nanosilymarin of 10, 100, and 1,000 µg/kg b.wt and a dose of free silymarin of 100 mg/kg b.wt intraperitoneally (i.p.) for 7 days. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) model on the eighth day for 1 h followed by 24 h reperfusion. The animals were then evaluated for neurobehavioral, infarct analysis, biochemical, histopathological, and immunohistochemical studies. All the above parameters showed remarkable improvement in nanosilymarin-treated groups in comparison to the silymarin-treated group. Nanoparticle encapsulation of drug enhanced neuroprotection by increasing drug bioavailability and targeting. Thus, the present study concluded with satisfactory results, showing the critical role played by nanoparticles in improving the neuroprotection at very low drug doses.

Collagen-curcumin nanocomposites showing an enhanced neuroprotective effect against short term focal cerebral ischemia.

The effectiveness of curcumin in treating cerebral ischemia has been reported in recent studies. However, its mode of action is still not defined. The objective of the present study is to formulate collagen-curcumin nanocomposites which will work effectively against cerebral ischemia/reperfusion injury. Ischemic injury is followed by inflammatory damage and oxidative stress, which together contribute a lot in the pathogenesis of cerebral ischemia and may be considered a good target for treatment. The present study focused on examining the effectiveness of collagen-curcumin nanocomposites stabilized by increasing the degree of crosslinking in reducing oxidative stress associated with brain injury resulting from cerebral ischemia. The collagen nanoparticles were prepared by conjugating collagen on the surface of Tween©80 micelles, and further stabilizing them using crosslinkers. The effectiveness of the prepared nanocomposite was validated by performing infarct analysis followed by biochemical, behavioral, histopathological and immunohistochemical studies. The outcomes of this study are promising for the use of collagen-curcumin nanocomposites in showing neuroprotective potential in treating ischemic injury.

Synthesis and Characterization of Zero-Valent Iron Nanoparticles, and the Study of Their Effect against the Degradation of DDT in Soil and Assessment of Their Toxicity against Collembola and Ostracods.

Of late, novel magnetic nanomaterials have drawn worldwide attention because of the uniqueness in their properties and uses. In our studies, we have prepared nearly monodisperse zero-valent iron nanoparticles (nZVIs) of diameter of less than 60 nm in aqueous medium by a reductive precipitation process and pectin as stabilizing agent. The characterization of these nanoparticles was done by dynamic light scattering and transmission electron microscopy (TEM) techniques. The TEM images confirmed that the average size of the nZVIs was about 25 nm. The resultant nZVIs were then employed to degrade DDT (dichlorodiphenyltrichloroethane) in spiked soil, and their toxicity toward Collembola (Folsomia candida) and Ostracods (Heterocypris incongruens) was measured. The fabricated nZVIs degraded DDT in soil quite effectively. Further, the effects of nZVIs on Collembola and Ostracods were found to be negative. This was due to the oxidation of nZVIs and creation of anoxic conditions thereupon, and the generation of excess Fe(II) in soil. In addition, the negative effects of DDT on ostracod development and Collembola reproduction were found to be quite weak.

Hierarchically Grown NiO-Decorated Polyaniline-Reduced Graphene Oxide Composite for Ultrafast Sunlight-Driven Photocatalysis.

Polymers and transition-metal oxides have gained great interest as a photocatalyst in environmental remediation. They could be modified with each other in order to improve their activity. Here, a sunlight-responsive hierarchically structured ternary composite of nickel oxide, polyaniline, and reduced graphene oxide (NiO@PANI/RGO) has been synthesized and employed as a catalyst for dye [methylene blue (MB)] degradation. PANI/GO synthesized by interfacial polymerization acts as a matrix for the growth of NiO using a microemulsion solvothermal method, ensuing an in situ reduction of graphene oxide during the formation of a hierarchical NiO@PANI/RGO composite. Morphological studies of the as-synthesized NiO@PANI/RGO composite reveal fine NiO (10 nm) nanoparticles intercalated between the uniformly grown PANI spines (50-60 nm) over the RGO surface. The optical band gap of ∼1.9 eV calculated from the UV-vis spectrum illustrates the extended light absorption range for the NiO@PANI/RGO photocatalyst. The efficiency of 98% MB degradation within 11 min with the degradation rate constant 0.086 min-1 for NiO@PANI/RGO has surpassed any other report on metal oxide/graphene-based ternary composites. Overall, this work could pave the way for the fabrication of futuristic hierarchical structured ternary nanocomposites as an efficient photocatalyst and facilitate their application in the environmental protection issues.

Enhancement in the Neuroprotective Power of Riluzole Against Cerebral Ischemia Using a Brain Targeted Drug Delivery Vehicle.

Riluzole is the only available drug for motor neuron diseases quite well-known for its neuroprotective activity. But its poor aqueous solubility, short half-life with some side-effects at higher concentration poses a limitation to its use as a therapeutic agent. The present study was performed to investigate the therapeutic potential of nanoriluzole (NR), i.e., riluzole encapsulated in nanoparticles against cerebral ischemia (stroke) at three different concentrations [10 (NRL), 20 (NRM), and 40 (NRH) µg/kg body weight intraperitoneally (i.p.)]. Chitosan conjugated NIPAAM (N-isopropylacrylamide) nanoparticles coated with tween80 were synthesized through free radical polymerization. The particles were characterized with Transmission Electron Microscopy, Dynamic Light Scattering, and Fourier Transform Infrared spectroscopy and were found to have size of ∼50 nm. Cerebral ischemia was induced by Middle Cerebral Artery Occlusion (MCAO) model for 1 h and NR was given intraperitoneally after 1 h of MCAO. Animals were dissected after a reperfusion period of 24 h for evaluation of various parameters. Triphenyl tetrazolium chloride staining shows substantial reduction in infarct size in all three treated groups. It was also supported by histopathological results, biochemical parameters, and behavioral studies. Immunological parameters like NOS-2, NF-kB, and COX-2 also show profound reduction in expression in NR treated groups. Thus, the present work clearly demonstrated that the nanoparticle was good enough to carry large amount of drug across the Blood Brain Barrier which results in significant neuroprotection even at a very low concentration. It also substantially lowered the required concentration by overcoming the poor aqueous solubility; hence hardly leaving any scope for side-effects.

Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-ß-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl4)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.

Size- and shape-dependent clinical and mycological efficacy of silver nanoparticles on dandruff.

Dandruff is a prominent scalp problem caused by the growth of fungus Malassezia furfur, potentially cascading into dermal inflammation, itching, and tissue damage. The present work outlines a detailed analysis of the treatment of scalp infection using silver nanomaterials (Ag NMs), and focuses on biocidal activity owing to manipulation of size, shape, and structure. Monodisperse silver spherical nanoparticles (NPs) and nanorods (NRs) were synthesized by chemical routes that were characterized using analytical and spectroscopic techniques. Ag NMs demonstrated enhanced biocidal tendencies compared to market available drugs, itracanozole and ketoconazole, showing greater zones of inhibition. The obtained 20 nm and 50 nm spherical-shaped NPs and 50 nm NRs showed concentration-, size-, and shape-dependent antifungal activity, with 20 nm spherical-shaped NPs exhibiting excellent potency. Minimum inhibitory concentration for 20 nm was lowest at 0.2 mg/mL in comparison to 0.3 mg/mL for NRs. Primary irritation index was 0.33 and 0.16 for 20 nm and 50 nm spherical-shaped NPs, respectively, while 50 nm rod-shaped NMs exhibited negligible redness. An in vivo model for M. furfur infection was generated by passing fungi subcutaneously in rats' skin. Again, 20 nm particles showed best normalization of skin after 10 days on regular dosing, in comparison with bigger and rod-shaped particles. The statistical clinical score was highest for Ag nanorods, followed by 50 nm Ag NPs-treated animals. It was observed that 20 nm spherical particles exhibited the lowest score (0) compared with others as well as with antifungal drugs. Biochemical analysis performed by checking antioxidant enzymatic activities indicated tissue repair and normalization of enzymes and protein concentration by Ag NPs.

Modulation of liver and kidney toxicity by herb Withania somnifera for silver nanoparticles: a novel approach for harmonizing between safety and use of nanoparticles.

In the present study, toxicity of nanoparticles is evaluated for assessing their effect on liver and kidney. We have synthesized highly mono-disperse spherical and rod-shaped silver nanoparticles using reverse microemulsion and aqueous phase methods. These were characterized by UV-vis spectrophotometer, dynamic light scattering, and transmission electron microscope confirming the formation of different sizes of spherical-shaped and rod-shaped silver nanoparticles (Ag NPs). Acute toxicity of different shapes and sizes of Ag NPs and their modulations by using Withania somnifera were evaluated through biochemical and histopathological changes in liver and kidney tissues of Wistar rats. We also evaluated cytotoxicity in specific murin macrophages through confocal microscopy. Cytotoxicity analysis indicates that median lethal dose (LD50) for 20, 50, and 100-nm size spherical and 100-nm rod-shaped Ag NPs was 0.25, 0.35, 0.35, and 0.35 mg/ml, respectively. We also calculated clinically important protein concentration to illustrate the efficacy of Ag nanomaterials. These studies indicated that 20, 50, and 100-nm spherical Ag NPs (35 mg/kg, 23 days) increased the biochemically important enzymes and substrate levels glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), creatinine, and urea concentration in serum, showing liver and kidney tissue damage. After 23 days of treatment of Ag NPs (20, 50, and 100 nm spherical), along with W. somnifera, toxicity of Ag NPs significantly decreased and marginalized. However, no significant changes were observed for 100-nm rod-shaped Ag NPs on normal liver and kidney architecture. Given their low toxic effects and high uptake efficiency, these have a promising potential as to lower the toxicity of Ag NPs.

Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: a randomized controlled trial.

OBJECTIVE: The aim of this study is to evaluate the effect of oral glutamine (GL) supplementation on gut permeability and endotoxemia (surrogate end point) in patients with severe acute pancreatitis. METHODS: In a randomized controlled trial, patients were randomized to be given placebo or GL for 7 days. The primary outcome measures include the effect on gut permeability (assessed by lactulose/mannitol excretion in urine and endotoxemia assessed by endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM). The secondary outcome measures include infectious complications, mortality, total hospital/intensive care unit stay, C-reactive protein, and prealbumin levels. RESULTS: Patients were assigned to GL (n = 41) and placebo (n = 39) groups. There was no change in gut permeability after the intervention. However, the EndoCab IgM levels increased significantly (33 [4, 175] to 40 [8, 350] GMU/mL; P = 0.0164) and the C-reactive protein levels decreased significantly (133 [1, 287] to 88 [1, 267] ng/mL; P = 0.0236) in the GL group. No difference was observed in infectious complication, prealbumin value, hospital/intensive care unit stay, and mortality in both groups. CONCLUSIONS: No significant trend was identified for an effect of GL on gut permeability. Decreased inflammation and endotoxemia did not translate into reduced infectious complications in severe acute pancreatitis. However, the study was underpowered to detect the aforementioned difference (trial registration: CTRI/2009/000945).

Intestinal permeability and complications in liver cirrhosis: A prospective cohort study.

AIM: Increased intestinal permeability (IP) has been implicated as an important factor for bacterial translocation (BT), leading to bacteremia and endotoxemia, resulting in various septic complications, variceal bleeding (VB), hepatic encephalopathy (HE), hepatorenal syndrome (HRS) and death in patients with liver cirrhosis (LC). This study was planned to assess IP in patients with LC and follow them for the occurrence of complications. METHODS: Patients with Child B and C cirrhosis without a history of disease-related complications were followed up for 6 months. IP was measured by lactulose and mannitol excretion ratio (LMR) in patients and 50 healthy controls (HC). Serum endotoxin levels were also assessed in 48 patients and 20 HC. RESULTS: Eighty patients (74 male), 41 (51.3%) Child B and 56 (70%) Child C, with a mean age of 40.7 ± 9.8 years were enrolled. IP was increased in 28 (35%) patients. LMR of patients was higher than HC (patients vs HC = 0.0238 [0.0010-1.557] vs 0.0166 [0.0018-0.720]; P = 0.007]. No significant difference was seen in the LMR of patients among various Child classes and etiologies. Serum endotoxin levels (GMU/mL) were higher in patients than HC (patients vs HC = 1.42 [0.68-2.13] vs 0.994 [0.067-1.382]; P = 0.001), but comparable between patients with abnormal and normal IP. At follow up, there was no significant difference in the incidence of complications like spontaneous bacterial peritonitis, HRS, VB, HE and death between patients with abnormal and normal IP. CONCLUSION: IP was increased in 35% of patients with LC; however, it was not associated with a higher incidence of disease-related complications.

Nanothymoquinone, a novel hepatotargeted delivery system for treating CCl4 mediated hepatotoxicity in rats.

Thymoquinone (TQ) is the major active principle of Nigella sativa (N. sativa) which is widely being used as a hepatoprotective agent nowadays. However, toxicity at high doses with poor water solubility limit its usage as a therapeutic agent. The idea behind the present study is to design a nanocarrier that exploits the benefit of the antioxidant property of TQ without any toxicity. For this purpose, PAG (p-aminophenyl-1-thio-ß-d-galactopyranoside) coated NIPAAM (N-isopropyl acrylamide) nanoparticles are synthesized followed by encapsulation of TQ (NTQ) in their hydrophobic core. PAG is a ligand which directly interacts with asialoglycoprotein receptors (ASGP-R) present on the surface of hepatocytes and delivers the drug directly to the liver. NTQ have a size of ∼100 nm and were characterized using IR, NMR, DLS, and TEM. The drug was given in two modes: one as NTQ (3 groups: 0.125 (NTQL), 1.25 (NTQM) and 12.5 (NTQH) µg kg-1 body weight, intraperitoneal (i.p.)) and the other as TQ (12 500 µg kg-1 body weight, i.p.). The best results were obtained with NTQH which is around 1000 times lower than TQ in concentration. Serum and biochemical parameters followed by restoration of histopathology supported this. Expression of inflammatory enzyme COX-2 and NF-kB also gave evidence in support.

Synthesis and characterization of gold nanorods and their application for photothermal cell damage.

BACKGROUND: Gold nanorods show a surface plasmon resonance (SPR) band at the near infra-red (NIR) region which enables them to produce heat on irradiation with a NIR laser. As a result of this, gold nanorods have the potential to be used as thermal therapeutic agents for selective damage to cancer cells, bacterial cells, viruses, and DNA. METHODS: Gold nanorods with an aspect ratio of approximately 5 were prepared by exploiting the normal micellar route of a water/dioctyl sulfosuccinate (Aerosol-T)/hexane system. The shape and size of the gold nanorods were characterized by surface plasmon bands at 520 nm and 980 nm, and by atomic force microscopy and transmission electron microscopy. RESULTS: The length of the gold nanorods was 100 nm and their diameter was 20 nm. X-ray diffraction analysis demonstrated that the gold nanorods formed were metallic in nature. The gold nanorods showed good photothermolysis activity. CONCLUSION: Gold nanorods injected subcutaneously and irradiated with 980 nm laser caused injury to rat tissue, demonstrating that gold nanorods may be used to kill cancerous cells in tumor tissue.

Antileishmanial activity of nanocurcumin.

BACKGROUND: Leishmaniasis is an endemic disease having a wide spectrum ranging from visceral, cutaneous and mucocutaneous forms caused by unicellular, obligate intracellular parasites of the monocyte-macrophage system. The aim of the present study was to develop an effective, nontoxic and biodegradable polymeric drug-delivery system encapsulating curcumin in its hydrophobic core for the treatment of visceral leishmaniasis. RESULTS: We have reported a co-polymeric micelle of N-isopropyl acrylamide, vinyl pyrrolidone and acrylic acid in 85:10:5 M ratios through free radical polymerization. The characterization of curcumin-loaded nanoparticles (40-50 nm) was done by transmission electron microscopy, dynamic light scattering and spectroscopic methods such as NMR which ensures polymerization and formation of nanoparticles has been achieved. Nanocurcumin was evaluated as an antileishmanial agent through spleenomegaly and delayed-type hypersensitivity experiments. CONCLUSION: Nanocurcumin has shown significantly greater in vivo therapeutic efficacy than pentamidine and free curcumin in an animal model of visceral leishmaniasis. The use of nanocurcumin compared with conventional drugs and free curcumin may prove more feasible and provide a better approach towards treatment of leishmaniasis.