Assessing the potential of lignin nanoparticles as drug carrier: Synthesis, cytotoxicity and genotoxicity studies.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.

Characterization of the rumen and fecal microbiome in bloated and non-bloated cattle grazing alfalfa pastures and subjected to bloat prevention strategies.

Frothy bloat is an often fatal digestive disorder of cattle grazing alfalfa pastures. The aim of this study was to investigate ruminal and fecal microbiota dynamics associated with development of alfalfa-induced frothy bloat and to further explore how bloat prevention strategies influence the composition of these microbial communities. In a 3 × 3 crossover experiment, twelve rumen-cannulated steers were sequentially subjected to: (1) pure alfalfa pasture, (2) pure alfalfa pasture supplemented with the pluronic detergent ALFASURE, and (3) alfalfa - sainfoin mixed pasture. Eleven out of 12 steers in pure alfalfa pasture developed clinical bloat, whereas ALFASURE treatment prevented the development of bloat in all 12 steers and alfalfa - sainfoin prevented bloat in 5 out of 11 steers. Development of bloat was associated with considerable shifts in the microbiota profile of rumen contents. In particular, the microbiota of solid rumen contents from bloated steers contained higher species richness and diversity. Streptococcus, Succinivibrio and unclassified Myxococcales were enriched in the rumen microbiota of bloated steers, whereas Fibrobacter and Ruminococcus were overrepresented in the rumen contents of non-bloated steers. Our results provide novel insights into bloat-associated shifts in the composition and predicted functional properties of the rumen microbiota of cattle grazing alfalfa pasture.

In Vitro Toxicity Evaluation of Lignin-(Un)coated Cellulose Based Nanomaterials on Human A549 and THP-1 Cells.

A significant amount of research toward commercial development of cellulose based nanomaterials (CNM) is now in progress with some potential applications. Using human A549 and THP-1 cells, we evaluated the biological responses of various CNMs, made out of similar material but with functional and morphological variations. While A549 cells displayed minimal or no cytotoxic responses following exposure to CNMs, THP-1 cells were more susceptible to cytotoxicity, cellular damage and inflammatory responses. Further analysis of these biological responses evaluated using hierarchical clustering approaches was effective in discriminating (dis)-similarities of various CNMs studied and identified potential inflammatory factors contributing to cytotoxicity. No correlation between cytotoxicity and surface properties of CNMs was found. This study clearly highlights that, in addition to the source and characteristics of CNMs, cell type-specific differences in the recognition/uptake of CNMs along with their inherent capability to respond to external stimuli are crucial for assessing the toxicity of CNMs.

Nasobronchial allergy and pulmonary function abnormalities among coir workers of Alappuzha.

BACKGROUND: Coir is a commercially important natural fiber obtained from the coconut husk. Coir can be woven into strong twine or rope, and is used for padding mattresses, upholstery, etc. Coir industry provides a major share of occupation to the natives of Alappuzha district of Kerala State. It has been noticed earlier that there is increased incidence of nasobronchial allergy among the population involved in this industry. OBJECTIVES: This study was aimed at recognizing the symptomatology and pulmonary functional impairment among symptomatic coir workers. DESIGN: All coir workers who attended our institute over a period of three years were included in the study. Detailed occupational history was taken; symptom profile was studied in detail, clinical examination and pulmonary function tests conducted. RESULTS: Among the 624 symptomatic coir workers selected for this purpose, 64 patients had purely nasal symptoms, while 560 had symptoms of nasobronchial allergy. 357 patients had reversible obstruction on PFT, while 121 had only small airway obstruction. CONCLUSIONS: We conclude that coir work induced nasobronchial allergy and pulmonary function abnormalities. In absence of CT scan and bronchial challenge testing it may be inappropriate to label coir work as occupational hazard. However the present study may be used as thought provoking study to initiate further understanding.

Integrity of gastric mucosa in reared piglets--effects of physical form of diets (meal/pellets), pre-processing grinding (coarse/fine) and addition of lignocellulose (0/2.5%).

The aim of the present study was to investigate the potential effects of different particle fractions in non-pelleted (meal) and pelleted diets on the development of pre-ulcerative gastric alterations. Furthermore, the effect of increased crude fibre supply (lignocellulose) on the integrity of gastric mucosa were investigated. For that purpose, 49 piglets were divided into eight feeding groups and fed pelleted diets differing in grinding intensity (very coarse/coarse/fine/very fine) and addition of lignocellulose (0/2.5%) for 6 weeks. A coarsely ground meal was used as control diet. Mucosal integrity of the pars non-glandularis was characterised by macroscopical and histological score and basal epithelial conductance. Feed structure was assessed by sieve analysis (wet/dry). The use of coarsely ground meal (25% >2 mm, 29% <0.4 mm) had almost no negative effects on the gastric wall: three of seven pigs had slight histological and none had macroscopical lesions. Irrespective of the original grinding intensity before pelleting, offering pelleted diets led to mucosal changes similar in severity (one out of seven pigs fed coarsely ground and pelleted diets had no macroscopical alterations, whereas all pigs fed finely ground and pelleted diets showed altered tissues). Increasing the proportion of coarse particles in the pellet (from 25 to 29% >2 mm) did not show any ulceroprotective effect. An increase of crude fibre content (42-54 g/kg dm) by adding lignocellulose did not result in a decreased ulcerogenity. Unpelleted diets are recommended as more favourable for alleviating the problem of gastric ulcers in pigs as the pelleting process is equal to a secondary grinding process. According to our results, an upper level of fine particles seems to be reasonable (a minimum level of coarse particles is not ulceroprotective). In this study, an amount of 30% <0.4 mm resulted in higher risks for ulcerations.

Uso do óxido crômico e do LIPE® na estimativa do consumo de matéria seca por bezerros de corte / Use of chromic oxide and LIPE® as external markers to estimate dry matter intake by beef calves

Avaliou-se a eficiência do óxido crômico e da lignina purificada e enriquecida (LIPE®), fornecidos uma vez ao dia, para a estimativa do consumo de matéria seca (CMS). Foram utilizados 12 bezerros de corte, de ambos os sexos, com uma média de idade de 210 dias e peso médio de 168kg, pastejando Brachiaria decumbens, distribuídos em um delineamento inteiramente ao acaso, em esquema de parcelas subdivididas. Os valores estimados de consumo, entre machos e fêmeas, foram semelhantes nos dois tratamentos. Entre os indicadores, as estimativas, da produção fecal e do consumo, foram menores para o óxido crômico. O CMS de forragem, o CMS total, o CMS em relação ao peso vivo e o CMS em relação ao peso metabólico, estimados pelos indicadores óxido crômico e LIPE®, foram, respectivamente, 2,03 e 4,50kg; 2,71 e 5,18kg; 1,62 e 3,10 por cento e 58,10 e 111,32g/kg PV0,75. O consumo estimado pelo LIPE® foi mais condizente com as exigências e com o desempenho observado nos animais.

Six male and six female calves, seven-month-old, averaging 168kg bw, grazing on Brachiaria decumbens, were used in a split plot design to compare the efficacy of two external markers: chromic oxide (Cr2O3) and purified and enriched lignin (LIPE®) simultaneously dosed once a day to predict dry matter intake (DMI). For both, Cr2O3 and LIPE®, no differences in DMI according to gender were observed. Comparing the efficacy of the two markers to predict fecal output and pasture intake, the estimates obtained with chromic oxide were lower. Forage DMI, total DMI, DMI as percentage of body weight, and DMI in relation to metabolic weight were: 2.03 and 4.50kg; 2.71 and 5.18kg; 1.62 and 3.10 percent, and 58.10 and 111.32g/kg bw0.75 for Cr2O3 and LIPE®, respectively. These results suggest that estimates obtained from LIPE® were more appropriate to the dry matter requirements and performance of the calves.

[Hygienic evaluation of hydrolytic lignin waste, by using alternative test models].

Chemical analysis showed that lignin samples contained phenols, phenanthrene, and methanol. The highest total content of organic compounds was noted in the lignin samples taken directly at a manufacturing plant. Phenols prevailed in the upper layers of stored lignin samples and methanol predominated in the lower ones. Studies on Tetrahymena pyriformis infusoria indicated that the fresh lignin samples are most toxic. A number of the samples exerted pronounced cytotoxic and genotoxic effects when the mollusks Limneae stagnalis and murine embryonic fibroblasts were examined.

[Investigation of allergenic properties of olipiphat]. / Issledovanie allergicheskikh svoistv olipifata.

Olipiphat, which is experimentally capable of antitumor action, did not induce any immediate hypersensitivity, but lowered such response to horse serum; nor did it stimulate delayed hypersensitivity to full Freund adjuvant or sharp venous return after concavalin A. No skin or eye mucosa irritation was reported.

[Ecological and hygienic evaluation of the lignin by-products utilization]. / Ekologo-gigienicheskaia otsenka produktov utilizatsii ligninnykh otkhodov.

Main trends in utilization of lignin wastes formed in complex wood processing are discussed. Toxicological and hygienic characteristics of lignins and products of their biotransformation and chlorination are presented. Ecology and hygiene of fertilizers, preserving agents, and construction materials based on lignins are evaluated.