Salivary biochemical markers as potential acute toxicity parameters for acute radiation injury: A study on small experimental animals.

Researchers have been evaluating several biodosimetric/screening approaches to assess acute radiation injury, related to mass causality. Keeping in mind this background, we hypothesized that effect of whole-body irradiation in single fraction in graded doses can affect the secretion of various salivary components that could be used as acute radiation injury/toxicity marker, which can be used in screening of large population at the time of nuclear accidents/disaster. Thirty Sprague Dawley rats treated with whole-body cobalt-60 gamma irradiation of dose 1-5 Gy (dose rate: 0.95 Gy/min) were included in this study. Whole mixed saliva was collected from all animals before and after radiation up to 72 h postradiation. Saliva was analyzed for electrolytes, total protein, urea, and amylase. Intragroup comparison of salivary parameters at different radiation doses showed significant differences. Potassium was significantly increased as the dose increased from 1 Gy to 5 Gy (p < 0.01) with effect size of difference (r > 0.5). Sodium was significantly altered after 3-5 Gy (p < 0.01, r > 0.5), except 1 and 2 Gy, whereas changes in sodium level were nonsignificant (p > 0.5). Urea, total protein, and amylase levels were also significantly increased as the radiation dose increased (p < 0.01) with large effect size of difference (r > 0.5). This study suggests that salivary parameters were sensitive toward radiation even at low radiation dose which can be used as a predictor of radiation injury.

Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aß42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain.

Impact of polymeric nanoparticles on oral pharmacokinetics: a dose-dependent case study with estradiol.

The present study reports the significance of polymeric nanoparticles in oral drug delivery from pharmacokinetic perspective. Impact of different dose polymeric nanoparticulate formulations on various pharmacokinetic parameters has been reported. All nano-formulations were found to have significant effect on important pharmacokinetic parameters like C(max), T(max), AUC, absolute bioavailability, absorption rate constant (K(a)), elimination rate constant (K(el)), elimination half life (t(1/2)), mean residence time (MRT) and mean absorption time (MAT). Further, drug in polymeric nanoparticles exhibited the flip-flop pharmacokinetics suggesting its slow and sustained release from the polymeric matrix. Together, polymeric nanoparticles hold promise for the oral delivery of molecules having pharmacokinetic hurdles in their delivery approach.

Pharmacodynamic evaluation of oral estradiol nanoparticles in estrogen deficient (ovariectomized) high-fat diet induced hyperlipidemic rat model.

PURPOSE: It is believed that estrogen deficiency contributes importantly to the pathogenesis of menopausal metabolic syndrome and symptoms can be ameliorated with estradiol therapy. The present study reports efficacy of 17-beta estradiol encapsulated nanoparticles in treating the postmenopausal dyslipidemic condition. MATERIALS AND METHODS: Estradiol encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles were prepared by emulsion-diffusion-evaporation method and evaluated in estrogen deficient (ovariectomized) high fat diet induced hyperlipidemic rat model. RESULTS: The results obtained showed that estradiol nanoparticles were equally/more effective in treatment of estrogen deficient hyperlipidemic conditions at three times reduced dose and frequency in comparison to that of drug suspension administered orally. CONCLUSION: Together, these results demonstrate the ability of nanoparticles in improving oral bioavailability/efficacy of estradiol.

Inactivation of MS2 F(+) coliphage on lettuce by a combination of UV light and hydrogen peroxide.

The efficacy of a produce decontamination method based on a combination of UV light (254 nm) and hydrogen peroxide (H2O2) to inactivate the MS2 F(+) coliphage inoculated onto iceberg lettuce was evaluated. Lettuce inoculated with 6.57 log PFU of MS2 was reduced by 0.5 to 1.0 log unit when illuminated with UV light alone for 20 to 60 s (12.64 to 18.96 mJ/cm2). In contrast, a 3-log reduction in MS2 was achieved with 2% (vol/vol) H2O2 spray delivered at 50 degrees C. No significant increase in log count reduction (LCR) was observed when H2O2 and UV light were applied simultaneously. However, H2O2 sprayed onto lettuce samples for 10 s, followed by a further 20-s UV illumination, resulted in an LCR of 4.12 that compares with the 1.67 obtained with 200 ppm of calcium hypochlorite wash. No further increase in MS2 inactivation was achieved by the use of either longer H2O2 spray or UV illumination times. The extent of MS2 reduction was significantly (P < 0.05) decreased when the H2O2 spray was delivered at 10 or 25 degrees C compared with 50 degrees C. In the course of aerobic storage at 4 degrees C, lettuce treated with UV light and H2O2 (10 or 25 degrees C) developed discoloration (polyphenol accumulation) within 6 days. In contrast, lettuce treated with UV light and H2O2 at 50 degrees C developed less discoloration within this time period and was comparable to untreated controls. This study demonstrated that the combination of UV light and H2O2 represents an alternative to hypochlorite-based washes to reduce the carriage of viruses on fresh produce.

PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug.

The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 +/- 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 +/- 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 +/- 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.

Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo.

The present investigation was aimed at optimization of estradiol loaded PLGA nanoparticulate formulations resulting in improved oral bioavailability and sustained release of estradiol by varying the molecular weight and copolymer composition of PLGA. Nanoparticles were prepared following emulsion-diffusion-evaporation method employing didodecyldimethyl ammonium bromide (DMAB) as stabilizer. The effect of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) has been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release was obtained with low molecular weight (14,500 and 45,000 Da) PLGA, while high molecular weight (85,000 and 213,000 Da) and different copolymer compositions followed square root of time (Higuchi's pattern) dependent release. The bioavailability of estradiol from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg estradiol/rat. The in vivo performance of the nanoparticles was found to be dependent on the particle size, polymer molecular weight and copolymer composition. The C(max) of drug in the plasma was dependent on the polymer molecular weight and composition while particle size was found to influence the duration of release, suggesting smaller is better. The histopathological examination revealed absence of any inflammatory response with the formulations prepared of low/high molecular weight or high lactide content polymers for the studied period. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of estradiol having great potential to address the dose related issues of estradiol.

Protective role of dietary fibre on N-nitrosopyrrolidine-induced toxicity in hypercholesterolemic rats.

N-nitrosopyrrolidine (NPYR) is an important carcinogen, frequently present in the environment and food chain. Oral administration of NPYR to experimental rats evoked severe biochemical and pathological changes. In the present investigation, the protective role of dietary fibre on NPYR-induced toxicity in hypercholesterolemic rats was studied. Supplementation of chickpea seed coat fibre in the diet reduced the hepato-toxic effects of NPYR, as evident from the decreased hepatic degeneration and improved liver weight index compared to control. Administration of NPYR resulted in an increase in the osmotic fragility of erythrocytes in the experimental animals. The antioxidant potential of experimental animals decreased in the NPYR-fed group, which was evident from the increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NPYR. Administration of NPYR resulted in a substantial and significant increase in LPO in all tissues, to a varying degree, though the effect was maximum in the case of the liver. Inclusion of chickpea seed coat fibre considerably reduced the peroxidative damage caused by NPYR in all tissues. The effect of NPYR administration on antioxidant potential was variable in different tissues, but the effect was reduced considerably on inclusion of chickpea seed coat fibre in the diet, providing reasonable protection against NPYR-induced oxidative stress, and, hence, its toxicity. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups. However, the pathological effects of NPYR administration were markedly reduced with the addition of chickpea seed coat fibre in the diet.

Efficacy of radio frequency cooking in the reduction of Escherichia coli and shelf stability of ground beef.

The effectiveness of radio frequency (RF) cooking on the inactivation of Escherichia coli in ground beef and its effect on the shelf stability of ground beef were investigated with a comparison to hot water-bath cooking. E. coli K12 was used as a target bacterium instead of E. coli O157:H7. The ground beef samples inoculated with E. coli K12 (ampr) were heated until the centre temperature of each sample reached 72 degrees C. These samples were then stored at 4 degrees C for up to 30 days. The enumeration of E. coli K12, background E. coli and coliform counts in ground beef samples was carried out for shelf-life study. Although both methods significantly reduced E. coli K12 (ampr), E. coli and coliform counts and extended the shelf-life, RF cooking had a shorter cooking time, and more uniform heating. Thus, RF cooking of meat has a high potential as a substitute for the hot water-bath cooking.

Carcinoid tumor of bile duct.

We report a 38-year-old lady with carcinoid tumor of the extrahepatic biliary tract who presented with recurrent obstructive jaundice and previous surgery for suspected choledocholithiasis. MRCP revealed a large bile duct tumor extending from the confluence up to the superior aspect of the pancreas; this was completely excised, with bilio-enteric anastomosis. These tumors are characteristically slow growing and, therefore, are amenable to aggressive surgical excision, which offers the best chance of cure.

Radio frequency cooking of ground, comminuted and muscle meat products.

The effect of radio frequency (RF) cooking, on the quality (colour, water holding capacity, texture), heating rate, and temperature history of three types of meat products (ground, comminuted and muscle), was investigated after heating to centre temperature of 72 °C in a 1.5 kW RF heater operating at 27.12 MHz. The results were compared with that obtained from heating in a water bath. RF cooking of processed meat products resulted in a decreased cooking time (5.83, 13.5, and 13.25 min for ground beef, comminuted meat, and muscle, respectively compared to 151, 130, and 109 min in water bath), lower juice losses, acceptable colour, water holding capacity and texture. The results indicate that when using RF, ground beef has the highest power efficiency (60.17%) followed by comminuted meat (44.41%), and muscle (43.38%). However, the texture of ground beef was too chewy and elastic. The muscle's colour was inferior. The comminuted and muscle meat products exhibited average energy efficiency with improved texture. The comminuted meat displayed a large cross-sectional temperature differential, possible due to uneven salt distribution. The well mixed comminuted and ground meat products appeared to be most promising for RF cooking.

Treatment of AA amyloidosis in rheumatoid arthritis.

Four patients of rheumatoid arthritis (RA) with biopsy confirmed AA amyloidosis were treated with chlorambucil. All had established but uncontrolled RA with a persistently raised ESR. Moderate (> 1 gm, < 3.5 gm/d) to nephrotic range (> 3.5 gm/d) proteinuria and a relatively well preserved renal function was noted in three patients. One patient had deranged renal function and required dialysis. On chlorambucil, there was complete recovery, partial improvement and no improvement in one patient each. The fourth patient required haemodialysis, did not tolerate chlorambucil and succumbed to the illness. Therapy with chlorambucil can benefit some patients of RA with AA amyloidosis. Leucopenia is the most important dose limiting side effect.

Adrenal histoplasmosis.

A 60 year old diabetic was admitted with the history of low grade fever and weight loss of six weeks duration. After investigations, he was detected to have bilateral adrenal masses which on biopsy proved to be due to histoplasmosis. He was treated with itraconazole and made complete recovery.

Neuroleptic malignant syndrome occurring in a suspected case of systemic lupus erythematosus.

The case of a 40 year old female patient of SLE who developed fatal neuroleptic malignant syndrome following administration of serenase (haloperidol) is reported. Relevant literature has been reviewed.

'Sustained remission' in a case of SLE following megadose cyclophosphamide.

Cytotoxic therapy, especially with cyclophosphamide in the dose 8-20 mg/kg used as intermittent pulses, has been shown to improve both patient and renal survival in systematic lupus erythematosus (SLE), but to date there is no cure for the disease. Owing to the paucity of recognisable clones, the rationale and goal of cytotoxic immunosuppressive therapy in the treatment of immune-mediated diseases as against malignancies is to suppress the aberrant inflammation and immune-mediated reactions responsible for tissue damage, without dangerously suppressing the normal host defence mechanism(s). We report the case of a patient suffering from SLE with nephritis who has remained in sustained remission over the past 8 years without any maintenance therapy following an accidental administration of a single dose of 5000 mg of intravenous cyclophosphamide (44.2 mg/kg body weight). The patient recovered fully from pancytopenia following the injection. Presently, she is asymptomatic and working gainfully. Her laboratory parameters including blood counts, urine analysis, FANA and anti-dsDNA have reverted to normal. Cyclophosphamide in the dose of 30-160 mg/kg has been safely and effectively used in various neoplastic conditions with the aim of destroying every possible tumour cell. The experience of the present case suggests that such an approach may be applicable to SLE.

Regulating the use of degraded oil/fat in deep-fat/oil food frying.

During frying, the degradation of oil produces harmful compounds. Improper monitoring of oil-discard times in restaurants either risks the public health or causes financial losses to industries. Measuring the oil quality is a complex problem and an online sensor is needed. The process of frying reviewed includes moisture, heat and fat/oil transfer, crust formation and various structural, textural and chemical changes in the product, and degradation of frying medium. Some of the European nations and the U.S. have specific regulations against the use of deteriorated frying oils. Due to the absence of a suitable online frying oil quality sensor for restaurant situations, it is difficult to implement any regulation against the use of deteriorated frying oil. Based on various regulations, a model regulation to increase the safety and quality of fried foods is discussed. Background and requirements for developing an online sensor to measure frying oil quality are discussed. Other related areas reviewed in this article are factors affecting oil penetration and absorption by the food, surfactant theory of frying, analytical indices, quick tests and acceptability of frying oil.