Orally fed EGCG coronate food released TiO2 and enhanced penetrability into body organs via gut.

Owing to unique nano-scale properties, TiO2-NPs (T-NPs) are employed as food-quality enhancers in >900 processed food products. Whereas, epigallocatechin-3-gallate (EGCG), a green tea polyphenol is consumed in traditional brewed tea, globally. Taken together, we aimed to investigate whether human gastric-acid digested T-NPs and complex tea catechins yield ionic species (Ti4+, Ti3+ etc.) and active EGCG forms to meet favourable conditions for in vivo bio-genesis of EGCG-coronated TiO2-NPs (ET-NPs) in human gut. Secondly, compared to bare-surface micro and nano-scale TiO2, i.e., T-MPs and T-NPs, respectively, how EGCG coronation on ET-NPs in the gut facilitates the modulation of intrinsic propensity of internalization of TiO2 species into bacteria, body-organs, and gut-microbiota (GM), and immune system. ET-NPs were synthesized in non-toxic aqueous solution at varied pH (3-10) and characterised by state-of-the-arts for crystallinity, surface-charge, EGCG-encapsulation, stability, size, composition and morphology. Besides, flow-cytometry (FCM), TEM, EDS, histopathology, RT-PCR, 16S-rRNA metagenomics and ELISA were also performed to assess the size and surface dependent activities of ET-NPs, T-NPs and T-MPs vis-a-vis planktonic bacteria, biofilm, GM bacterial communities and animal's organs. Electron-microscopic, NMR, FTIR, DLS, XRD and EDS confirmed the EGCG coronation, dispersity, size-stability of ET-NPs, crystallinity and elemental composition of ET-NPs-8 and T-NPs. Besides, FCM, RT-PCR, 16S-rRNA metagenomics, histopathology, SEM and EDS analyses exhibited that EGCG coronation in ET-NPs-8 enhanced the penetration into body organs (i.e., liver and kidney etc.) and metabolically active bacterial communities of GM.

Dosimetric analysis of intracavitary brachytherapy applicators: a practical study.

PURPOSE: Intracavitary brachytherapy is one of the important methods of gynecological cancer treatment. The effect of attenuation is not considered in the dose calculation method released by the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43). In this study, the effect of high-dose rate (HDR) brachytherapy applicators on dose distribution was measured using Gafchromic films and well-type ionization chamber. MATERIALS AND METHODS: A plan created by the treatment planning system was first executed using a well-type ionization chamber with a water equivalent elasto-gel in place for charge collection. Again, same plan was executed using central tandems of various angulations with different diameters of vaginal cylinders and charge collection was measured. For in vitro dose measurements this plan was also executed on tandem and vaginal cylinder assembly with Gafchromic films fixed on the surface of vaginal cylinder. RESULTS: The results show that the central tandem when used with different vaginal cylinders resulted in increase in effective attenuation of the beam. The central tandem of 300 angulations when used with a 35-mm diameter vaginal cylinder results in maximum attenuation whereas the 0º tandem when used with 20-mm diameter vaginal cylinder results in least attenuation of the beam. CONCLUSION: Due to the attenuation by various applicators used in brachytherapy for the treatment of gynecological cancers, it can be concluded that the difference between practical dose and the treatment planning system calculated dose should be considered for the correct estimation of the dose to the target and the organs-at-risk.

Tremor after long term lithium treatment; is it cortical myoclonus?

INTRODUCTION: Tremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult. METHODS: We identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum. RESULTS: Seven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42-77) after lengthy exposure to lithium (range 7-40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse. CONCLUSIONS: A synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.

Biochemical, histopathological, and transmission electron microscopic ultrastructural changes in mice after exposure to silver nanoparticles.

Four-week-old mice, weighing about 25-35 g were divided into five groups (8 mice in each group): vehicle control, low- (0.5 g/kg), middle- (1 g/kg), high- (3 g/kg), and exceptionally high-dose (5 g/kg). After first and second weeks of intraperitoneal exposure to AgNPs, biochemical, histopathological, and electron microscopic ultrastructural changes were investigated. No significant changes were observed in SGOT and ALP levels after first week of exposure, while the level of SGPT significantly increased (p < 0.05) in 2nd week treated mice, indicating that inflammatory of liver might be induced by high-dose (3 and 5 g/kg) of AgNPs. No obvious changes were observed for UA and BUN in all groups of treated mice. However, significant (p < 0.05) decrease in CR level was noticed in all groups of treated mice only at high-dose (3 and 5 g/kg). No remarkable changes in lipid profile were observed. Light microscopic histopathological investigation shows that first week treatment had not perceptible effect on the cytoarchitecture on liver, kidney, and spleen; while, second week treatment had only sporadic mild effects on these organs. However, no ultrastructural electron microscopic changes were observed in liver, kidney, and spleen of mice treated with 0.5, 1, and 3 g/kg of AgNPs when sacrificed on first and second week; while, exceptionally high-dose (5 g/kg) of AgNPs resulted in slight nuclear chromatin condensation and irregularities in nuclear membrane. The results suggested that AgNPs could be well tolerated in mice when given intraperitoneally and no death has been found during the experiment in any groups of treated mice. Interestingly, significant (<0.05) decrease in glucose levels in all experiment group is suggestive of curious hypoglycemic role of AgNPs warranting further study to explore its possible therapeutic potential in hyperglycemic conditions as well as its mechanism of action at molecular level. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 945-956, 2016.

Riboflavin Arrests Cisplatin-Induced Neurotoxicity by Ameliorating Cellular Damage in Dorsal Root Ganglion Cells.

Cis-Diamminedichloroplatinum II- (CP-) induced neurotoxicity is one of the least explored aspects of this drug. Dorsal root ganglia (DRG) cells are considered as the primary target, and their damage plays a vital role in pathogenesis and etiology of CP-induced neurotoxicity. The present study is aimed at confirming if riboflavin (RF) has any protective role in shielding the DRG from CP-induced toxicity. After conducting the established treatment strategy on mice under photoillumination, it was observed that, despite the fact that RF alone is partially toxic, its combination with CP significantly ameliorated the drug-induced damage in DRG cells as evidenced by histological analysis. In addition, it was interesting to observe that the combination group (RF + CP) was able to induce apoptosis in the target cells up to a significant extent which is considered as the most preferred way of countering cancer cells. Therefore, RF can act as an effective adjuvant compound in CP-based chemoradiotherapy to improve clinical outcomes in the contemporary anticancer treatment regimes.

Histomorphometry of preterm and term human placentas / Histomorfometría de placentas de pretérmino y término

The intra-uterine existence of foetus is dependent on placenta, a major organ of nutrition and homeostasis.The present study was carried out to compare morphometric and histological changes in preterm and term human placentas. Eighty placentas collected from Department of Obstetrics and Gynecology, JNMCH, AMU, Aligarh, were divided into group first of preterm placentas up to 36 weeks (n =30) and second group of full term placentas i.e. 37 to 40 weeks ( n = 50) respectively. The samples were fixed in 10 percent formol-saline solution. The gross morphological variables of placentas were studied. There was a significant increase in the placental weight, decidual area and umbilical cord diameter of term placenta as compared to that of the preterm ones. From each placenta whole thickness tissue blocks were taken and processed for paraffin sectioning. Five µ-thick sections were stained with Haematoxylin-eosin and Van Gieson stains and processed for light microscopy. A total of 200 villi were studied in each sample under high power field and occurrence of different features was expressed as percentages for each parameter. The appearance of microvilli and syncytial bud on the syncytium were almost absent in the villi of term placentas. It was concluded that with increasing gestational age there was a gradual increase in the number of capillaries in villi from preterm to term placenta.There was a significant increase in syncytial knot count, fibrinoid necrosis, vasculosyncytial membrane and decrease in the percentage of villi showing cytotrophoblastic cells and number of Hofbauer cells in term group as compared to preterm group.

La existencia intrauterina del feto depende de la placenta, el mayor órgano de nutrición y homeostasis. El estudio se llevó a cabo para comparar los cambios morfométricos e histológicos de la placenta humana de término y pretérmino. Ochenta placentas fueron obtenidas del Departamento de Obstetricia y Ginecología, JNMCH, AMU, Aligarh y se dividieron en grupos, el primer grupo de placentas de pretérmino hasta 36 semanas (n = 30) y el segundo grupo de placentas de término, de 37 a 40 semanas (n = 50 ). Las muestras fueron fijadas en solución de formol-salina al 10 por ciento. Se estudiaron las variables morfológicas macroscópicas de las placentas. Hubo un aumento significativo en el peso de la placenta, el área de decidua y el diámetro del cordón umbilical de la placenta a término en comparación con la de los prematuros. De cada placenta se tomaron y se procesaron bloques de tejido para incluirlos en parafina. Cortes de 5 µm fueron teñidos con HE y Van Gieson para microscopía óptica. De cada muestra fueron estudiadas 200 vellosidades, bajo campo de alta resolución y la aparición de diferentes características se expresó como porcentajes para cada parámetro. La aparición de las microvellosidades y brote sincitial en el sincitio estaban casi ausente en las vellosidades de las placentas de término. Se puede concluir que al aumentar la edad gestacional hubo un aumento gradual en el número de capilares en las vellosidades de la placenta de término. Existe un aumento significativo en el recuento de nudo sincitial, necrosis fibrinoide, membrana vasculosincisial y disminución en el porcentaje de las vellosidades que muestran células citotrofoblástica y número de células de Hofbauer en las placentas del término de grupo en comparación con el grupo de pretérmino.

Dosimetric Consistency of Co-60 Teletherapy Unit- a ten years Study.

OBJECTIVE: The goal of the Radiation standards and Dosimetry is to ensure that the output of the Teletherapy Unit is within ±2% of the stated one and the output of the treatment dose calculation methods are within ±5%. In the present paper, we studied the dosimetry of Cobalt-60 (Co-60) Teletherapy unit at Sher-I-Kashmir Institute of Medical Sciences (SKIMS) for last 10 years. Radioactivity is the phenomenon of disintegration of unstable nuclides called radionuclides. Among these radionuclides, Cobalt-60, incorporated in Telecobalt Unit, is commonly used in therapeutic treatment of cancer. Cobalt-60 being unstable decays continuously into Ni-60 with half life of 5.27 years thereby resulting in the decrease in its activity, hence dose rate (output). It is, therefore, mandatory to measure the dose rate of the Cobalt-60 source regularly so that the patient receives the same dose every time as prescribed by the radiation oncologist. The under dosage may lead to unsatisfactory treatment of cancer and over dosage may cause radiation hazards. Our study emphasizes the consistency between actual output and output obtained using decay method. METHODOLOGY: The methodology involved in the present study is the calculations of actual dose rate of Co-60 Teletherapy Unit by two techniques i.e. Source to Surface Distance (SSD) and Source to Axis Distance (SAD), used for the External Beam Radiotherapy, of various cancers, using the standard methods. Thereby, a year wise comparison has been made between average actual dosimetric output (dose rate) and the average expected output values (obtained by using decay method for Co-60.). RESULTS: The present study shows that there is a consistency in the average output (dose rate) obtained by the actual dosimetry values and the expected output values obtained using decay method. The values obtained by actual dosimetry are within ±2% of the expected values. CONCLUSION: The results thus obtained in a year wise comparison of average output by actual dosimetry done regularly as a part of Quality Assurance of the Telecobalt Radiotherapy Unit and its deviation from the expected output data is within the permissible limits. Thus our study shows a trend towards uniformity and a better dose delivery.

Cisplatin-induced neurotoxicity in vivo can be alleviated by riboflavin under photoillumination.

Cisplatin (CP)-induced neurotoxicity is one of the major clinical problems in CP-based chemoradiotherapy, leading to its discontinuation depending upon their severity. In the present investigation, the photosensitizing property of riboflavin (RF) has been used to ameliorate the CP-induced neurotoxicity. According to dosing plan, the healthy mice were given RF, CP, and their combinations under photoillumination with their controls without any light exposure. After the treatment, antioxidant enzymes, cellular reductants, glutathione-S-transferase, brain markers, and oxidation products were assessed besides histopathology in their brain samples. These parameters revealed that RF ameliorates CP-induced neurotoxicity in a dose-dependent manner under photoillumination. Hence, inclusion of RF in CP-based chemoradiotherapy can be an effective strategy to counter CP-induced neurotoxicity.

Characterization of clinical strains of MSSA, MRSA and MRSE isolated from skin and soft tissue infections and the antibacterial activity of ZnO nanoparticles.

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). MRSA is an important pathogen in the healthcare sector that has neither been eliminated from the hospital nor community environment. In humans, S. aureus causes superficial lesions in the skin and localized abscesses, pyogenic meningitis/encephalitis, osteomyelitis, septic arthritis, invasive endocarditis, pneumonia, urinary tract infections and septicemia. Investigations focused in the search of other alternatives for the treatment of MRSA infections are in progress. Among the range of compounds whose bactericidal activity is being investigated, ZnO nanoparticles (ZnO-NPs) appears most promising new unconventional antibacterial agent that could be helpful to confront this and other drug-resistant bacteria. The aim of present study is to investigate the antibacterial potential of ZnO-NPs against Staphylococcus species isolated from the pus and wounds swab from the patients with skin and soft tissue infections in a tertiary care hospital of north India. ZnO-NPs (≈19.82 nm) synthesized by sol-gel process were characterized using scanning electron microscopy, X-ray diffraction , and Atomic force microscopy. The antibacterial potential was assessed using time-dependent growth inhibition assay, well diffusion test, MIC and MBC test and colony forming units methods. ZnO-NPs inhibited bacterial growth of methicillin-sensitive S. aureus (MSSA), MRSA and methicillin-resistant S. epidermidis (MRSE) strains and were effective bactericidal agents that were not affected by drug-resistant mechanisms of MRSA and MRSE.

Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

Synthesis and characterization of the antibacterial potential of ZnO nanoparticles against extended-spectrum ß-lactamases-producing Escherichia coli and Klebsiella pneumoniae isolated from a tertiary care hospital of North India.

The reemergence of infectious diseases and the continuous development of multidrug resistance among a variety of disease-causing bacteria in clinical setting pose a serious threat to public health worldwide. Extended-spectrum ß-lactamases (ESBLs) that mediate resistance to third-generation cephalosporin are now observed all over the world in all species of Enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae. In this work, ZnO nanoparticles (NPs) were synthesized by the sol-gel method and characterized by powder X-ray diffraction, scanning electron microscopy (SEM) and atomic force microscopy (AFM). The image of synthesized ZnO NPs appeared spherical in SEM with a diameter of ≈19 nm and as hexagonal crystal in AFM. Clinical isolates were assessed for ESBL production and shown to be sensitive to ZnO NPs by different methods such as minimal inhibitory concentration (MIC) and minimal bactericidal concentration, time-dependent growth inhibition assay, well diffusion agar methods and estimation of colony forming units (CFU) of bacteria. The lowest MIC value for E. coli and K. pneumoniae was found to be 500 µg/ml. The results showed that ZnO NPs at 1,000 µg/ml completely inhibit the bacterial growth. The antibacterial effect of ZnO nanoparticles was gradual, but time- and concentration-dependent. The maximum inhibition zone at100 µg/ml for E. coli and K. pneumoniae was 22 and 20 mm, respectively. With the increasing ZnO NP loading, there is significant reduction in the numbers of CFU. At the concentration of 1,000 µg/ml, the decline in per cent survival of E. coli and K. pneumoniae was found to be 99.3% and 98.6%, respectively.

RD antigen based nanovaccine imparts long term protection by inducing memory response against experimental murine tuberculosis.

BACKGROUND: The absence of certain genomic loci that are present in most of the virulent strains of Mycobacterium tuberculosis as well as lack of lasting memory responses are some of the major causes attributed to the non effectiveness of Bacille Calmette-Gue'rin (BCG) vaccine. Immunization schedules addressing these issues can offer better strategy for protection against tuberculosis. METHODS: The immunological responses evoked upon administration of archaeosome based antigen delivery system comprising T cell antigen, Rv3619c (an ESAT-6 family protein), has been assessed against experimental murine tuberculosis in BALB/c mice. RESULTS: Archaeosome based subunit vaccine has been found to elicit type-1 cytokines in the immunized mice. Besides effective T cell memory response, the Rv3619c based vaccine was able to reduce mycobacterial burden in the animals challenged with Mycobacterium tuberculosis infection. CONCLUSION: The data of the present study suggest that archaeosome encapsulated RD gene products offer substantial protection against M. tuberculosis infection.

Tuftsin augments antitumor efficacy of liposomized etoposide against fibrosarcoma in Swiss albino mice.

Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma.

Focal dystonia after removal of a parietal meningioma.

A patient presented at the age of 50 years with a right-sided, writing-specific dystonia which settled without treatment. Ten years later she developed focal seizures affecting the right leg and occasionally spreading to the right arm. A left parietal meningioma was removed and 2 years later she developed dystonic movements of her right hand. Gliotic changes were seen on magnetic resonance imaging in the superficial left parietal lobe. Mechanisms involved in the generation of dystonia associated with cortical injury are discussed.