Thursday, 22 March 2018

Comparative Nano-indentation Creep Study of Ductile Metal, Ductile Polymer and Polymer-fly Ash Composite


Anew study is conducted under same experimental creep conditions to investigate and compare the response of dissimilar materials (metals, polymers and composites) in relation to properties such as hardness and (unloading) ‘reduced modulus’ on changing the nano-indentation test parameters. The research uses nano-indentation technique to determine the resistance to plastic deformation in these broadly different materials as a function of maximum load, holding time and loading rate. Wear rate and cutting efficiency of these materials are examined and it is found that only maximum load alters these properties in the three materials. Hardness and ‘reduced modulus’ are found to be directly affected by increase or decrease in maximum load, holding time and loading rate.

H: Hardness;Er: Effective Modulus; h: Indentation Depth; hmax: Maximum Indentation Depth at Maximum Load; hc: Indentation Depth in contact with Indenter; hp: Height of Sink-in/pile-up; he: Elastic Recovery Height after Unloading; hc/hmax: Degree of Sink-in/ pile-up; H/Er ²: Rate of wear or Resistance to Plastic Deformation; A: Area of Indentation; S: Stiffness; β: Correction Factor for Indentation Shape; n value: Work Hardening Coefficient Value.

A concept of determining the mechanical properties of material on nano scale has given rise to the development of a powerful depth sensing nano-indentation technique which is capable of studying the various material properties such as unloading ‘reduced’ modulus, hardness, creep properties, and fracture toughness. Nano-indentation test procedure involves application of predetermined load in the range of μN to mN with the help of either spherical or pyramidal indenter in order to produce the indentation of the order of a few microns (measured in terms of nano-meters), followed by controlled unloading. The contact area of indentation is used to calculate hardness (H) of the material and the slope of unloading curve on load-displacement can be used for determining the ‘effective’ modulus or ‘reduced’ modulus (Er). Later modification in the method was achieved by holding at maximum load constant for some time before unloading (creep). This modification was done in order to study the visco-elastic and visco-plastic behavior of the materials where conventional nano-indentation method was based on the assumption that material behave in an elastic-plastic manner.

Wednesday, 21 March 2018

LECT2 – A New Cause of Hepatic Amyloidosis


Amyloidosis is caused by an abnormal deposition and accumulation of insoluble protein fibrils in multiple organs, often leading to diverse clinical presentations, and possible organ failure. On Congo-Red staining, amyloid fibrils form characteristic betapleated sheets that typically show apple, green birefringence upon polarization under light microscopy. The kidney is the most common organ affected in systemic amyloidosis. The liver is involved less frequently than the kidney. In this editorial we present a recently discovered amyloid protein - LECT2 (leukocyte chemotactic factor 2) that has been documented to affect the kidney and the liver. Of more than 30 types of amyloid protein fibrils discovered thus far, LECT2 is one of the most recently described. It was initially reported to present with slowly progressive renal failure and nephrotic syndrome.
In the United States, LECT2 protein has been found to be especially prevalent among people of Hispanic ethnicity. In an autopsy series, LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanics, and could represent an important but under-recognized etiology of chronic kidney disease in this population. Two large case series focusing on renal amyloidosis identified LECT2 as the second and third most common form of renal amyloidosis respectively. LECT2 fibrils are found in the glomeruli, renal vessels, and interstitium. Other organs including the liver, spleen, adrenals, and lungs but not myocardium or brain have been reported to be involved with LECT-2 amyloid protein.
A recent large case series identified LECT2 as the second most common form of hepatic amyloidosis. In this series LECT2 accounted for up to 25% of hepatic amyloid cases. LECT2 is synthesized mainly by the liver and is considered to be a hepatokine. The exact biological function of LECT2 is not precisely known. In the liver, it acts as is an eutrophilic chemotactic factor. It also plays a role in hepatocyte regeneration. Increased expression of LECT2 has been found in hepato cellular tumors. The LECT2 gene has been mapped to chromosome 5q31.1-q32 by fluorescence in situ hybridization. This region contains a cluster of cytokine genes that include IL-4, IL-5, and IL-9. Recently it was discovered that LECT2 may play an important role in insulin resistance and may promote atherosclerosis. As such, it is also suggested to play a role in the development of fatty liver and obesity.
Hepatic amyloid, when identified, is usually located in the sinusoids, portal tracts, and arterioles. Various morphological patterns of amyloid including linear, globular and mixed types have been identified. The Globular Hepatic Amyloid (GHA) sub-type is composed of round to oval globules, 5 to 40 micrometer in diameter that are found within the space of Disse as well as aggregated within the portal tracts. Chandran et al. found that GHA, although uncommon, is highly sensitive and specific for LECT2 amyloidosis and was also found more often in Hispanics. LECT2 has been described in a patient with non-cirrhotic portal HTN. It is possible that deposition of GHA in the vascular spaces of the liver can cause obstruction of the blood flow at the sinusoidal level resulting in non-cirrhotic portal hypertension.

Tuesday, 20 March 2018

A New History: The 2016 Revision of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissuess


Classification is thelanguage of medicine: diseases must be described, defined and named before they can be diagnosed, treated and studied. However, a critical feature of any classification of diseases is that it be periodically reviewed and updated to incorporate new information. For many years the diagnosis of leukemia was based solely on pathologic and cytological examination of bone marrow and peripheral blood smears; however, this classification does not always reflect the genetic and clinical diversity of the disease. In this way, the World Health Organization (WHO) proposed a classification to recognize and classify different subgroups of leukemia through clinical, morphological and genetic correlation.
The “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues” is one of the “blue book” monographs published by the International Agency for Research on Cancer (IARC; Lyon, France), created in collaboration with the Society for Hematopathology and the European Association for Haematopathology. Eight years have elapsed since the current fourth edition of the monograph was published in 2008, and remarkable progress has been made in the field in this time period. Despite this, a truly new fifth edition cannot be published for the time being, as there are still other volumes pending in the fourth edition of the WHO tumor monograph series. Therefore, the Editors of the “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues,” with the support of the IARC and the WHO, decided to publish an updated revision of the fourth edition that would incorporate new data from the past 8 years which have important diagnostic, prognostic, and therapeutic implications.
The major changes in the classification and their rationale are presented by Swerdlow S. et al. and Arber D. et al. for lymphoid and myeloid neoplasm respectively, however it’s important to note that although some provisional entities have been promoted to definite entities and a few provisional entities have been added to the revised WHO classification, no new definite entities were permitted according to IARC guidelines. The current revision is a much needed and significant update of the 2008 WHO classificationto incorporate clinical features, morphology, immunophenotyping, cytogenetics, and molecular genetics to provide better diagnostic categories and criteria, together with biological and clinical correlates, and facilitate state-of-theart patient care, future therapeutic advances, and basic research in this field. The WHO effort to keep up-dating the classification will continue on, and hopefully provide a model of cooperation between clinicians, pathologists, scientists and hematologists from all over the world. In the field of leukemia, many questions remain unanswered, however, this update is the first step toward a closer integration of genetic data into a clinicopathological classification. Based in this, the journal “Austin Leukemia” aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Leukemia that could be the basis for future classifications.

Monday, 19 March 2018

Lung Cancer Activity of Caralluma Species, an Overview

Genus Caralluma a perineal herb of Asclepiadaceae family, it is used as traditional medicine for the treatment number of diseases like diabetes, inflammation, leprosy, obesity, rheumatism, diseases of the blood helminthic diseases, stomach disorders, abdominal pains, septics, chronic lung diseases, such as tuberculosis and cancer. We focus critical evaluation of genus Caralluma use in the lung cancer treatment in this review.

Uncontrolled cell division that spreads throughout the body is cancer; it’s a group of diseases which can lead to death if not controlled. External factors (tobacco, infectious organisms, and unhealthy diet) and internal factors (inherited genetic mutations, hormones, and immune conditions) are the main causes of cancer. These i.e. external and internal may act composed or in order resulting cancer, it may pass a decade from exposure to detection of cancer. Among all types of cancers lung and breast cancers are most diagnosed and leading cause of deaths in men and women. WHO report states that the common causes of cancer deaths are cancers of lung (1.59 million deaths), liver (745 000 deaths), stomach (723 000 deaths), colorectal (694 000 deaths), breast (521 000 deaths), oesophageal cancer (400 000 deaths). Mainly cancer arises from the interaction of person’s genetic factors and three types of external factors like physical carcinogens (Ultraviolet and Ionizing radiation), chemical carcinogens (Tobacco, asbestos, smoke, aflatoxin, and arsenic) and biological carcinogens (virus, bacteria and parasites). 

The incidence of cancer is more in developed nations than less developed nations but mortality is more (65%) in less developed nations. Prostate cancer in men and lung cancer in women is leading death cause of cancer in more developed Nations, the burden of cancer is slowly shifting to less developed Nations due to the aging of the population and increasing pervasiveness. The genus Caralluma of Asclepiadaceae comprises of approximately 350 species all around the globe. Genus Caralluma normally prefers a dry habitat and decay when they are exposed to an excess of water. The support may be necessary, as they do not contain fibrous tissue. Some of the plants grow even up to a height of 100 cm under protection. Review of literature revealed medicinal uses of genus Caralluma. The distribution of Carallumas ranges from the Mediterranean to East Indies, mostly found in Southern Europe, Iran, Iraq, African countries like Kenya, Somalia, Sudan and Ethiopia, Arabian countries like Oman, UAE and Yemen and Asian countries like Afghanistan, Pakistan, India, Nepal, Burma and Sri Lanka.

Saturday, 17 March 2018

From Bench to Bedside: The Growing Use of Arabinoxylan Rice Bran (MGN-3/Biobran) in Cancer Immunotherapy

MGN-3/Biobran is a denatured hemicellulose obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. Over the last 24 years, our fundamental research objective has been to study the biotherapeutic activity of MGN-3 as a treatment for cancer based on its ability to activate the immune system. This objective has been pursued in vitro, and in animal and human studies. This review is focused on the immunomodulatory effects of MGN-3 and on its potential as an anticancer agent. In vitro studies showed that culturing different human and murine cancer cell lines with MGN-3 resulted in a reduction of the survival rate of cancer cells. In vivo studies have also shown that MGN-3 induces tumor regression in several models of animal bearing tumor, including gastric cancer, neuroblastoma, and Ehrlich carcinoma. In addition, the anti-cancer activity of MGN-3 has been shown in human clinical trials and in several case reports on patients with Hepatocellular Carcinoma (HCC) and progressive and partially metastasized cancer. Patients that were treated with MGN-3 in addition to Conventional Therapy (CT), as compared with CT alone, showed: 1) less recurrence of cancer, 2) higher survival rate and 3) improved Quality of Life (QOL) as characterized by improvements in physical activity, appetite, sleep, and digestion, and a decrease in pain and anxiety.
This review summarizes the preclinical and clinical research on MGN-3/ Biobran since it was first patented in 1992. Various animal studies and human clinical trials including different types of malignancies have demonstrated that MGN-3 is a potent Biological Response Modifier (BRM). MGN-3 enhances the cytotoxic reactivity of immune cells with anti-cancer activity such as NK and CD8+ T cells via increasing cell granularity, stimulates the production of interferons, IL-2 and IL-12, and functions as a natural adjuvant for Dendritic Cells (DC). Therefore, MGN-3 may be used in DC-based vaccine strategies against infections and cancer. Importantly, MGN-3 is a unique BRM because it is a safe non-toxic agent and does not exhibit hyporesponsiveness. MGN- 3 has the potential to be a novel and promising immune modulatory adjuvant that could complement the existing immunotherapeutic modalities for cancer patients.
Despite the last decade of advances in treatment options, cancer remains the second leading cause of death in the United States. Unfortunately the outcome of standard cancer treatments is often poor due to the emergence of Multidrug Resistance (MDR) during the course of treatment. MDR cells are a significant factor in the failure of chemotherapeutics as evidenced by high relapse rates for the majority of patients. Therefore, to increase cancer survival and improve symptom control, there is a strong need for new and better approaches to cancer treatment. Today, the National Cancer Institute (NCI) has acknowledged the importance of immune therapy for the treatment of cancer. NCI, other health organizations, and professionals in the field of oncology are currently working to harness the immune system to fight cancer and to expand immunotherapy in combination with other types of cancer treatment, such as targeted therapy, chemotherapy, and radiation therapy.

Friday, 16 March 2018

Two Cases of Peritonitis due to Pantoea Species at One Center with Different Outcomes

Peritonitisis a serious complication of peritoneal dialysis. A variety of microorganisms are identified in these cases and during recent years a new one was included, Pantoea species. In our report, we present 2 cases of patients on CCPD with a peritonitis episode caused by this organism. The source of infection in one of the cases was thought to be due to gardening of the plant Basil, while unknown in the other case. In microbiologic culture, this organism was identified and the patients were started on antibiotics with success in one case while the other requiring catheter removal. The number of reported cases with this organism has increased in last years and various infection localizations and clinical progress patterns have been identified. In peritoneal dialysis patients presenting with peritonitis, this organism must be kept in mind.
For patients on peritoneal diaysis, peritonitis is an important cause of mortality and morbidity. The treating physician needs to keep a high index of suspicion and treat peritonitis early to improve outcome and reduce complications. While usual gram positive and gram negative organisms make most of the cases, recently one unusual environmental gram negative family appeared to be the cause. The organism Pantoea, belongs to the family Enterobacteriaceae and is responsible for infectious diseases mainly from plant-thorn injuries, causing arthritis, osteoitis, osteomyelitis to bacteremia. Until now a number of clinical cases of peritonitis caused by this organism have been described. We present two cases (Case A and B) of peritonitis with Pantoea species at our center, both of which had different course and outcomes requiring different treatments.
Upon evaluation, there was diffuse abdominal tenderness but there were no signs of exit site or tunnel infection. The PD fluid was found to be cloudy and analysis showed White cell count of 1000 with 92% neutrophils. Other investigations revealed serum WBC count 7.6k/ul, ESR 30mm/hr, CRP 0.4mg/dl, Lactic acid 3.1mmol/L. Patient was started on empirical treatment including Intraperitoneal Ceftriaxone and Vancomycin. The Blood cultures were negative; however the PD fluid culture grew Pantoea species sensitive to Cephalosporins, Gentamycin and Tazobactam. The patient showed significant improvement and disappearance of symptoms on the third day. The PD fluid WBC dropped to 22k/ul with normalization of ESR and lactic acid levels and the fluid culture became negative after 5 days of treatment. Patient was discharged home and he completed 14 days of antibiotic therapy. Over the next one year, patient did not have any further episodes of peritonitis, and the repeated PET test did not show any changes on the membrane characteristics.

Thursday, 15 March 2018

Response of Potato to Water Stress in Southern Serbia


Aninvestigation was carried out on alluvium soil type in the river valley of Southern Morava, Southern Serbia during the seasons of 2008 and 2009, aiming to determine the response of potato to soil water deficit, using yield response factor. The values of yield response factor were derived from the linear relationship between relative seasonal evapotranspiration deficits and relative yield loss. Values of seasonal crop response factor of 1.14 indicate that potato is moderately sensitive to soil water stress in the climatic conditions of the Southern Serbia. Seasonal evapotranspiration was 495.0 mm and 291.2 mm in irrigated and rain-fed conditions respectively. A linear relationship was found between seasonal evapotranspiration and tuber yield. Potato yield in the variant with irrigation was 48.31 t ha-1 or 88.3% higher than in the variant without irrigation.

Production of potato (Solanum tuberosum L.) takes a very important place in world agriculture, with a production potential of about 368 million t harvested and 19.3 million ha planted area with an average yield of 19.1 t ha-1. Potato production ranks fourth in the world after rice, wheat and maize. In Serbia potato is grown at about 77,000 ha with an average yield of 10.2 t ha-1, and total production of 786,000 tones. In southern Serbia potato crop land is 55,000 ha with an average yield of 9.2 t ha-1, and total production of 55,000 tones. The yield of potato in Serbia is fourth times lower than this achieved in the leading potato growing countries. The low yields are the consequence of inadequate management practices, insufficient amount and unfavorable arrangement of precipitation in the growing season and inappropriate irrigation scheduling applied. In Serbia potato is cultivated under both irrigated and non-irrigated conditions. Portable sprinkler irrigation systems are commonly used. Due to the unpredicted amount and distribution of precipitation in the growing season, irrigation in Serbia is mainly supplemental. It is used primarily to supplement infrequent or irregular precipitation during drought periods.
Several authors and research groups reported results of experiments aimed at determining optimum soil moisture under different environmental and technical conditions. Bošnjak and Pejić, Milić et al., Pejić et al. found that the lower limit of optimum soil moisture for potatoes is 70% of field water capacity when this crop is grown in a soil with medium texture. Wright and Stark, King and Stark, Costa et al.  indicated that maximum yield of high quality potato tubers could only be achieved if the soil’s available water in the maximum active root zone would not drop below the 50% limit.