Administration Of NP Research Articles

Effect of metal nanoparticles usage on oxidative stress indicators and endotoxemia parameters under DMH-induced carcinogenesis

One of the properties of nanoparticles is their ability to correct manifestations of oxidative stress and endotoxemia, which are critical factors in cancer development. Therefore, the work aimed to investigate the effect of the usage of Au/Ag/Fe nanoparticles on oxidative stress indicators and endotoxemia parameters in experimental colon carcinogenesis. The study was performed on 90 white male rats kept in standard vivarium conditions. The division into groups: I – intact animals; II – intact animals with 21 days NPs administration; III – animals injected with N,N-dimethylhydrazine dihydrochloride for 30 weeks; ІV – animals to which Au/Ag/Fe nanoparticles were intragastrically administered daily for 21 days after induced adenocarcinoma. According­ to our results, the concentration of oxidative stress indicators significantly increases under DMH-induced carcinogenesis conditions. It was established that the 21-day intragastric administration of NP Au/Ag/Fe composition caused a significant (P < 0.001) decrease in the concentration of TBARS in the blood serum by 1.33 times, in the content of diene and triene conjugates by 1.63 and 1.98 times, respectively compared to the third experimental group. The introduction of NPs in the fourth experimental group reduces the concentration of the Schiff bases by 1.34 times (P < 0.001), decreases the content of POMP370 and POMP430 by 1.25 (P < 0.001) and 1.37 times (P < 0.001), respectively, compared to the third experimental group. We also observed the reduction of endotoxemia levels in a fourth experimental animal group based on a significant decrease in MMM indexis and EII percentage. Keywords: Au/Ag/Fe nanoparticles, endotoxemia, induced colon carcinogenesis, N‚N-dimethylhydrazine dihydrochloride, oxidative stress

Preparation and characterization of curdlan-chitosan conjugate nanoparticles as mucosal adjuvants for intranasal influenza H1N1 subunit vaccine

Intranasal vaccination offers crucial protection against influenza virus pandemics. However, antigens, especially subunit antigens, often fail to induce effective immune responses without the help of immune adjuvants. Our research has demonstrated that a polyelectrolyte complex, composed of curdlan sulfate/O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (CS/O-HTCC), effectively triggers both mucosal and systemic immune responses when administrated intranasal. In this study, stable nanoparticles formed by curdlan-O-HTCC conjugate (CO NP) were prepared and characterized. Furthermore, the efficacy of CO NP was evaluated as a mucosal adjuvant in an intranasal influenza H1N1 subunit vaccine. The results revealed that CO NP exhibits uniform and spherical morphology, with a size of 190.53 ± 4.22 nm, and notably, it remains stable in PBS at 4 °C for up to 6 weeks. Biological evaluation demonstrated that CO NP stimulates the activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), both in vitro and in vivo. Furthermore, intranasal administration of CO NP effectively elicits cellular and humoral immune responses, notably enhancing mucosal immunity. Thus, CO NP emerges as a promising mucosal adjuvant for influenza subunit vaccines.

Bindarit encapsulated nanoparticles prevent venous neointimal hyperplasia and restenosis in a murine angioplasty model

Monocyte and macrophage recruitment occur to the injured vessel wall after percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVF) through increased expression of MCP-1 leading to venous neointimal hyperplasia (VNH) and venous stenosis (VS). We hypothesized that adventitial delivery of Bindarit, an oral selective inhibitor of MCP-1, -2, and -3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (BN NP) could prevent VNH/VS formation in a murine model of PTA with AVF. Scanning electron microscope and dynamic light scattering were used to characterize the BN NP and control nanoparticles (NP C). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to study drug release kinetics. Immediately after PTA, in a murine model of AVF stenosis, BN NP or NP C was administrated to the adventitia of outflow veins. Animals were sacrificed 3 and 21 days later for gene expression, histomorphometric, and immunohistochemical analyses. Doppler ultrasound was performed weekly. There was no difference in the size and storage modulus of BN NP compared to controls. The pharmacokinetic analysis demonstrated increased drug release from BN NP when compared to controls. BN NP-treated vessels had reduced MCP-1, MCP-2, and MCP-3 gene, and protein levels, reduced macrophage/monocyte abundance, proinflammatory cytokines, and venous fibrosis resulting in positive vascular remodeling and improved patency with reduced VNH/VS. There was increased peak velocity 21 days after PTA in the BN NP group. Adventitial administration of BN NP to the outflow vein after PTA results in decreased VNH/VS.

Nanoformulated Bumetanide Ameliorates Social Deficiency in BTBR Mice Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with few medication options. Bumetanide, an FDA-approved diuretic, has been proposed as a viable candidate to treat core symptoms of ASD, however, neither the brain region related to its effect nor the cell-specific mechanism(s) is clear. The availability of nanoparticles provides a viable way to identify pharmacological mechanisms for use in ASD. Here, we found that treatment with bumetanide, in a systemic and medial prefrontal cortex (mPFC) region-specific way, attenuated social deficits in BTBR mice. Furthermore, using poly (ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(bumetanide)], we showed that the administration of NP(bumetanide) in a mPFC region-specific way also alleviated the social deficits of BTBR mice. Mechanistically, the behavioral effect of NP(bumetanide) was dependent on selective microglia-specific targeting in the mPFC. Pharmacological depletion of microglia significantly reduced the effect of nanoencapsulation and depletion of microglia alone did not improve the social deficits in BTBR mice. These findings suggest the potential therapeutic capabilities of nanotechnology for ASD, as well as the relevant link between bumetanide and immune cells.

PHARMACOLOGICAL ACTIVITY OF COMBINATION OF CURCUMIN AND VITAMIN C AGAINST OXIDATIVE STRESS INDUCED BY NAPROXEN IN MALE RATS

The Aim: The goal of this study was to see if curcumin and vitamin C might protect male rats' blood from oxidative stress caused by naproxen using hematological criteria and antioxidant measures.
 Study Design: The rats were aged 2.5-3 months and contemplated (200-250) gm. The purpose of this study was to see if Cur and Vitamin C might protect male rats against oxidative damage caused by NP, as well as hematological.
 Place and Duration of Study: From April to October 2019, the experiment was conducted out on 48 male rats weighing between (200-250) gm and aged 2.5-3 months at the animal house of the faculty of science/university of Kufa.
 Methodology: The 48 male Wister albino rats were separated into six groups at random; Group (1) NP was administered orally to rats at a dose of 40 mg/kg (as positive control). Group (2) cur at a dose of 150 mg/kg was given orally to the rats as a treatment. Group (3) During a 14-day period, rats were given 150 mg/kg of vitamin C by oral administration. Group (4) cur (150 mg/kg) and Vitamin C (150 mg/kg) were given orally to the rats as a treatment. Group (5) The oral administration of NP (40 mg/kg) plus Cur (150 mg/kg) plus Vit C (150 mg/kg) was performed on rats. Group (6) normal saline solution was given to the rats orally during the experiment (as negative control).
 Results: Finishing the experiments, the findings displayed a considerable decrease (p<0.05) in the average of body weight, hemoglobin concentration (HB) and haematocrit ( HCT) while considerable increase (p<0.05) in the white blood cells(WBC) counts in the animals treated with NP compared to the control and other treated groups , while the results offered considerable increase (p <0.05) in the average of body contemplate , HB, HCT and a considerable decrease (p<0.05) in WBC rate in the animals treated with Cur, VitC, Cur+Vit C, Cur +Vit C+ Np compared the control group .
 Conclusion: In conclusion, whereas naproxen has a harmful impact on the body by increasing oxidative stress, curcumin and vitamin C operate as powerful antioxidant supplements that reduce malonal di aldehyde (MDA) and boost overall antioxidant capacity by increasing superoxide dismutase (SOD) in the body.

Oral administration of TiO2 nanoparticles during early life impacts cardiac and neurobehavioral performance and metabolite profile in an age- and sex-related manner

BackgroundNanoparticles (NPs) are increasingly incorporated in everyday products. To investigate the effects of early life exposure to orally ingested TiO2 NP, male and female Sprague–Dawley rat pups received four consecutive daily doses of 10 mg/kg body weight TiO2 NP (diameter: 21 ± 5 nm) or vehicle control (water) by gavage at three different pre-weaning ages: postnatal day (PND) 2–5, PND 7–10, or PND 17–20. Cardiac assessment and basic neurobehavioral tests (locomotor activity, rotarod, and acoustic startle) were conducted on PND 20. Pups were sacrificed at PND 21. Select tissues were collected, weighed, processed for neurotransmitter and metabolomics analyses.ResultsHeart rate was found to be significantly decreased in female pups when dosed between PND 7–10 and PND 17–20. Females dosed between PND 2–5 showed decrease acoustic startle response and when dosed between PND 7–10 showed decreased performance in the rotarod test and increased locomotor activity. Male pups dosed between PND 17–20 showed decreased locomotor activity. The concentrations of neurotransmitters and related metabolites in brain tissue and the metabolomic profile of plasma were impacted by TiO2 NP administration for all dose groups. Metabolomic pathways perturbed by TiO2 NP administration included pathways involved in amino acid and lipid metabolism.ConclusionOral administration of TiO2 NP to rat pups impacted basic cardiac and neurobehavioral performance, neurotransmitters and related metabolites concentrations in brain tissue, and the biochemical profiles of plasma. The findings suggested that female pups were more likely to experience adverse outcome following early life exposure to oral TiO2 NP than male pups. Collectively the data from this exploratory study suggest oral administration of TiO2 NP cause adverse biological effects in an age- and sex-related manner, emphasizing the need to understand the short- and long-term effects of early life exposure to TiO2 NP.

T. brucei infections abrogate diverse plasma cell-mediated effector B cell responses, independently of their specificity, affinity and host genetic background.

Antibody-mediated parasite killing is considered the most effective host immune response against extracellular trypanosome parasites. However, due to host-parasite co-evolution pressure, these parasites have “learned” how to hijack the host immune system via the development of immune evasion strategies. Hereby they prevent elimination and promote transmission. In the past, our group has shown that African trypanosome parasites are able to “shut down” the host B cell compartment, via the abolishment of the homeostatic B cell compartment. In line with this, we have reported that trypanosome infections result in detrimental outcomes on auto-reactive and cancer B cells. To unravel the immune mechanisms involved in these processes we adopted here a well-defined B cell vaccine model, i.e. the thymo-dependent hapten-carrier NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin) emulsified in Alum adjuvant. Results show that T. brucei infections abrogate the circulating titres of vaccine-induced CGG-specific as well as NP-specific IgG1+ antibodies, a hallmark of memory B cell responses in this model. This happens independently of their affinity and IFNɣ signalling. Next, we demonstrate that T. brucei infections also induce a decrease of anti-NP IgG3+ antibodies induced by the administration of NP coupled to Ficoll, a thymo-independent antigen. Confirming the non-specificity of the infection-associated immunopathology, this report also shows that trypanosome infections abolish vaccine-induced memory response against malaria parasite in BALB/c mice. Together, these data indicates that T. brucei infections impair every stages of B cell development, including effector plasma B cells, independently of their specificity and affinity as well as the host genetic background.

Possible involvement of alpha B-crystallin in the cardioprotective effect of n-butanol extract of Potentilla anserina L. on myocardial ischemia/reperfusion injury in rat

BackgroundIt has been reported that n-butanol extract of Potentilla anserina L (NP) had protective effect against acute myocardial ischemia/reperfusion (I/R) injury in mice. Because of limited phytochemical study on NP, its bioactive compounds and underlying protective mechanisms are largely unclear. PurposeThe purpose of this study was to investigate the major bioactive compounds and possible mechanism for the cardioprotective effect of NP on rat with I/R injury. MethodsWe analyzed the phytochemical isolation of NP and identified the structure of compounds, which was elucidated by a combination of spectroscopic analyses. An I/R model was established by I-30 min/R-2 h in Sprage-Dawley rats. The rats were given intragastric administration of NP (49.3, 98.6, and 197.2 mg•kg−1) continuously for 10 days before I/R operation. The morphological changes and apoptosis of cardiomyocytes were observed by H&E staining, Transmission electron microscope and TUNEL staining respectively. The activities or contents of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in plasma were detected. Apoptosis related factors were also measured by RT-PCR and western blot. In order to discover the underlying mechanism of NP on I/R, we performed proteomic analysis using two-dimensional gel electrophoresis (2D-DIGE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) to describe differential proteins expression. Potential target protein resulted from 2D-DIGE coupled to MALDI-TOF/MS analysis were further confirmed by immunohistochemical staining, RT-PCR, and western blot. ResultsWe isolated and identified 14 compounds, of which 7 compounds belong to triterpenes. Rats pretreated with NP showed a significant increase on the activities of GSH, SOD and CAT, and remarkable decrease on the content of MDA. NP significantly inhibited the apoptosis of cardiomyocyte and decreased the expression of Cyt C and cleaved-caspase-3. Proteomic analysis revealed that alpha B-crystallin (CryAB) might participate in the NP protective effect against I/R. NP enhanced the level of pCryAB Ser59, whereas the expression of CryAB was decreased. ConclusionNP was showed to alleviate I/R injury and inhibit myocardial apoptosis, which might be associated with reduction on oxidative stress and apoptosis. CryAB as a possible target involved in the NP protective effect. This study supplied valuable information to develop novel cardioprotective agents from NP extract.

Effect of curcumin nanoparticles on the cisplatin-induced neurotoxicity in rat

The present study is conducted to evaluate the neuroprotective effect of curcumin nanoparticles (CUR NP) against the neurotoxicity induced by cisplatin (CP) in rat. Rats were divided into control group that received saline solution, CP-treated rats that received a single i.p. injection of CP (12 mg/kg body wt), and CP-treated rats that received a single i.p injection of CP (12 mg/kg body wt) followed by a daily oral administration of CUR NP (50 mg/kg body wt) for 14 days. At the end of the experiment, the motor activity of rats was evaluated by open field test. The neurochemical and histopathological changes were investigated in the cerebral cortex. A significant decrease in motor activity was observed in CP-treated rats. This was associated with a significant increase in the cortical levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, caspase-3, and acetylcholinesterase activity. However, CP induced a significant decrease in reduced glutathione levels and Na+, K+-ATPase activity. In rats treated with CP and CUR NP, no significant changes were recorded in the parameters of the open field test as compared to control. In addition, treatment with CUR NP prevented all the neurochemical changes induced by CP except the increased value of nitric oxide. CUR NP also reduced the histopathological changes induced by CP. It is clear from the present data that CUR NP could ameliorate the neurotoxic effect induced by cisplatin.

A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer.

Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metal-inducible and stress-inducible genes, stress kinase cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration. Cancer Res; 77(11); 2964-75. ©2017 AACR.

Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model.

TiO2 nano-particle (TiO2 NP) is widely used in industrial, household necessities, as well as medicinal products. However, the effect of TiO2 NP on liver metabolic function has not been reported. In this study, after mice were orally administered TiO2 NP (21nm) for 14days, the serum and liver tissues were assayed by biochemical analysis, real time quantitative polymerase chain reaction, western blot and transmission electron microscopy. The serum bilirubin was increased in a dose dependent manner. Deposition of TiO2 NP in hepatocytes and the abnormality of microstructures was observed. Expression of metabolic genes involved in the endogenous and exogenous metabolism was modified, supporting the toxic phenotype. Collectively, oral administration of TiO2 NP (21nm) led to deposition of particles in hepatocytes, mitochondrial edema, and the disturbance of liver metabolism function. These data suggested oral administration disrupts liver metabolic functions, which was more sensitive than regular approaches to detect material hepatotoxicity. This study provided useful information for risk analysis and regulation of TiO2 NPs by administration agencies.

The Effect of Multiple Sclerosis on Carotid Baroreflex Control of Heart Rate and Blood Pressure

Multiple sclerosis (MS), a progressive neurological disease, can result in impairments in autonomic control of cardiovascular function. We tested the hypothesis that patients with MS (n=5) exhibit a blunted response following baroreflex perturbation compared to sex and age matched healthy controls (CON: n=5). At rest, 5‐sec pulses of neck suction (NS; ‐60 Torr) and neck pressure (NP; +40 Torr) were applied to simulate carotid hypertension and hypotension, respectively. Mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR) were continuously measured in response to the perturbations. Following NS, responses in MAP (MS: ‐11±5 mmHg, CON: ‐10±3 mmHg; p=0.59) and HR (MS: ‐8±3 BPM, CON: ‐8±4 BPM; p=0.93) were similar between groups. While HR response (MS: 5±5 BPM, CON: 5±4 BPM; p=0.94) following NP was no different, a difference in MAP approached significance (MS: 6±2 mmHg, CON: 8±2 mmHg; p=0.09). These data suggest that patients with MS demonstrate a diminished ability to increase MAP to hypotensive stimuli compared to healthy controls.
 Supported by NIH R15HL117224 and National MS Society RG4696A

DOX-MTX-NPs augment p53 mRNA expression in OSCC model in rat: effects of IV and oral routes.

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1- oxide induced OSCC. RESULTS showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX- MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

Preparation and Evaluation of Microemulsion Formulations of Naproxen for Dermal Delivery

Naproxen (Np) is an example of a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of pain and inflammation. In order to develop an alternative formulation for the topical administration of Np, microemulsions were evaluated as delivery vehicles. Four formulations were prepared using isopropyl myristate (IPM) as oil phase, Span 80, Labrafil M, Labrasol, Cremophor EL as surfactants, ethanol as co-surfactant and distilled water or 0.5 N NaOH solution as aqueous phase. The final concentration of Np in the microemulsion system was 100 mg/g (w/w). The physicochemical properties such as electrical conductivity, droplet size, viscosity, pH and phase inversion temperature of microemulsions were measured. Stability tests of the formulations were also performed at 5±2, 25±2 and 40±2°C. The abilities of various microemulsions and selected commercial (C) formulation to deliver Np through the skin were evaluated in vitro using diffusion cells fitted with rat skins. The in vitro permeation data showed that microemulsions increased the permeation rate of Np between 4.335-9.040 times over the C formulation. Furthermore Np successfully permeated across the skin from the microemulsion with the highest flux rate (1.347±0.005 mg·cm(-2)·h(-1)) from a formulation (M4Np) consisting of IPM (2.36 g), Labrosol (0.13 g), Span 80 (0.62 g), ethanol (5.23 g), 0.5 N NaOH solution (0.66 g) and Np (1 g). According to the histological investigations, no obvious skin irritation was observed for the studied microemulsions. These results indicate that the microemulsion formulation may be appropriate vehicles for the topical delivery of Np.

Intratracheal Administration of a Nanoparticle-Based Therapy with the Angiotensin II Type 2 Receptor Gene Attenuates Lung Cancer Growth

Targeted gene delivery, transfection efficiency, and toxicity concerns remain a challenge for effective gene therapy. In this study, we dimerized the HIV-1 TAT peptide and formulated a nanoparticle vector (dTAT NP) to leverage the efficiency of this cell-penetrating strategy for tumor-targeted gene delivery in the setting of intratracheal administration. Expression efficiency for dTAT NP-encapsulated luciferase or angiotensin II type 2 receptor (AT2R) plasmid DNA (pDNA) was evaluated in Lewis lung carcinoma (LLC) cells cultured in vitro or in vivo in orthotopic tumor grafts in syngeneic mice. In cell culture, dTAT NP was an effective pDNA transfection vector with negligible cytotoxicity. Transfection efficiency was further increased by addition of calcium and glucose to dTAT/pDNA NP. In orthotopic tumor grafts, immunohistochemical analysis confirmed that dTAT NP successfully delivered pDNA to the tumor, where it was expressed primarily in tumor cells along with the bronchial epithelium. Notably, gene expression in tumor tissues persisted at least 14 days after intratracheal administration. Moreover, bolus administration of dTAT NP-encapsulated AT2R or TNF-related apoptosis-inducing ligand (TRAIL) pDNA markedly attenuated tumor growth. Taken together, our findings offer a preclinical proof-of-concept for a novel gene delivery system that offers an effective intratracheal strategy for administering lung cancer gene therapy.

Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses

BackgroundThe sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, “universal” vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd) expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.Methodology/Principal FindingsIn BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Conclusion/SignificanceMucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study

BackgroundThe objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis.MethodsAn 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo were given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]).ResultsEighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 ± 2.3 vs 11.8 ± 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 ± 1.4 vs 9.9 ± 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 ± 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups.ConclusionIn this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contributing factor to the other benefits.

Phellodendron and Citrusextracts benefit cardiovascular health in osteoarthritis patients: a double-blind, placebo-controlled pilot study

BackgroundThe objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on cardiovascular protective properties in overweight and normal weight adults diagnosed with osteoarthritis of the knee.MethodsAn 8-week, placebo-controlled, randomized, double-blind study was conducted with four groups, comparing the effects of NP 06-1 to placebo in overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo was given in a dose of two capsules (370 mg each) twice daily. The outcome measures reported are lipid levels, weight, BMI, blood pressure and fasting glucose. Analyses of variance were used to compare changes of physiological measures over the trial period and between groups.ResultsEighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. NP 06-1 administration was associated with a general improvement in lipid levels. Both the overweight and normal weight treatment groups had significant reductions in triglycerides and LDL-cholesterol, as well as a significant increase in HDL-cholesterol compared to their respective control groups.Overall there were decreases in blood pressure in both overweight and normal weight treatment groups compared to respective placebo groups. There was also a significant decrease in fasting glucose levels in the overweight treatment group compared to the start of the study and to the overweight placebo group. There was no change in fasting blood sugar for the normal weight groups.Both overweight and normal weight treatment groups lost a significant amount of weight compared to their respective placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks, which was associated with a significant loss in BMI over time.ConclusionIn this pilot study NP 06-1 had a beneficial effect on cardiovascular risk factors; namely lipid levels, blood pressure and fasting glucose levels. Administration of NP 06-1 was also associated with weight loss.

Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages

The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle–indinavir (NP–IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP–IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP–IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide “proof of concept” for the use of macrophage-based NP delivery systems for human HIV-1 infections.

P-Nonylphenol pretreatment during the late neonatal period has no effect on 3,2′-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in male F344 rats

The modifying effects of late neonatal administration of p-nonylphenol (NP), a suspected xenoestrogen, on 3,2′-dimethyl-4-aminobiphenyl (DMAB)-induced prostatic carcinogenesis were investigated in male F344 rats. Three-week-old rats received 25, 250 or 2000 ppm of NP in the diet for 3 weeks prior to DMAB treatment and were sacrificed at 67 weeks of age for histopathological assessment of lesions and Ki-67 immunohistochemical analysis of cell cycle kinetics. Dietary administration of NP during the sexually immature period had no effects on maturation of male sex organs. Incidence, multiplicity and areas of neoplastic lesions in the prostate and seminal vesicles, and Ki-67 labeling indices in normal-looking epithelium were not significantly different among the experimental groups. These results indicate that late neonatal treatment with NP has no modulating effects on DMAB-induced rat prostatic carcinogenesis.