SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Offal

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Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals.

Concepts: Kidney, Liver, Renal cortex, Renin, Offal, Herbicide, Glyphosate, Roundup

27

Abstract Background: Malaria remains a major global health concern in developing regions of the world. Homeopathy, a holistic system of medicine, has a lot to offer in protecting against malaria. Methods: In the present study, antimalarial efficacy of combination of two homeopathic drugs Chelidonium 30 and nosode 30 has been evaluated in vivo against Plasmodium berghei (P. berghei) infection using Peters 4-day test. Biochemical assays have been performed to assess the levels of hepatic and renal function biomarkers upon drug treatment using diagnostic kits. Results: The combination of the drugs demonstrated considerable in vivo antimalarial activity with chemosuppression of 91.45% on day 7. The combination also significantly (p<0.0005) enhanced the mean survival time of mice which was calculated to be 22.5±6.31 days, whereas it was 8.55±0.83 days in infected control. The increase in levels of the liver function marker enzymes tested in serum of treated mice were significantly less (p<0.0005) than those observed in infected control on day 10. The serum urea and creatinine used for assessment of renal sufficiency were slightly elevated above normal, but were statistically significant (p<0.0005) as compared to infected control. Conclusions: The study establishes the effectiveness of the combination against P. berghei in vivo along with the safety of the drugs to the liver and kidney functions of the host.

Concepts: Kidney, Statistics, Blood urea nitrogen, Liver, Peritoneum, Urea, Offal, Homeopathy

27

Long-acting lanreotide (LAN) 120 mg every 4 weeks reduces liver volume (LV) in patients with polycystic liver diseases (PCLD). Animal studies demonstrated that the inhibition of hepatic and renal cystogenesis is dose dependent.

Concepts: Cancer, Glucose, Cirrhosis, Liver, Organ, Liver disease, Offal, Liver biopsy

27

Recently, organic-inorganic hybrids composed of derivatives of dextran, a polysaccharide, and magnetite nanoparticles have attracted much attention as novel thermoseeds. If they can be fabricated into microspheres of size 20-30 μm, they are expected to show not only hyperthermia effects but also embolization effects in human liver and kidney cancers. In this study, we examined the fabrication of carboxymethyldextran/magnetite microspheres using a water/oil emulsion as the reaction medium. Improvement of the chemical stability of the microcapsules by coating with silica using a sol-gel process was also investigated. The obtained hollow microspheres contained particles of size 20-30 μm. Silica coating using an appropriate catalyst for hydrolysis and polycondensation of alkoxysilanes was found to be effective for preventing dissolution and collapse in simulated body environments.

Concepts: Vitamin D, Glucose, Liver, Polymer, Sol-gel, Colloid, Peritoneum, Offal

27

Mouse serum alkaline phosphatase (ALP) is frequently measured and interpreted in mammalian bone research, however; little is known about the circulating ALPs in mice and their relation to human ALP isozymes and isoforms. Mouse ALP was extracted from liver, kidney, intestine, and bone from vertebra, femur and calvaria tissues. Serum from mixed strains of wild-type (WT) mice and from individual ALP knockout strains were investigated, i.e., Alpl(-/-) (a.k.a. Akp2 encoding tissue-nonspecific ALP or TNALP), Akp3(-/-) (encoding duodenum-specific intestinal ALP or dIALP), and Alpi(-/-) (a.k.a. Akp6 encoding global intestinal ALP or gIALP). The ALP isozymes and isoforms were identified by various techniques and quantified by high-performance liquid chromatography. Results from the WT and knockout mouse models revealed identical bone-specific ALP isoforms (B/I, B1, and B2) as found in human serum, but in addition mouse serum contains the B1x isoform only detected earlier in patients with chronic kidney disease and in human bone tissue. The two murine intestinal isozymes, dIALP and gIALP, were also identified in mouse serum. All four bone-specific ALP isoforms (B/I, B1x, B1, and B2) were identified in bone tissues from mice, in good correspondence with those found in human bones. All mouse tissues, except liver and colon, contained significant ALP activities. This is a notable difference as human liver contains vast amounts of ALP. Histochemical staining, Northern and Western blot analysis confirmed undetectable ALP expression in liver tissue. ALP activity staining showed some positive staining in the bile canaliculi for BALB/c and FVB/N WT mice, but not in C57Bl/6 and ICR mice. Taken together, while the main source of ALP in human serum originates from bone and liver, and a small fraction from intestine (<5%), mouse serum consists mostly of bone ALP, including all four isoforms, B/I, B1x, B1, and B2, and two intestinal ALP isozymes dIALP and gIALP. We suggest that the genetic nomenclature for the Alpl gene in mice (i.e., ALP liver) should be reconsidered since murine liver has undetectable amounts of ALP activity. These findings should pave the way for the development of user-friendly assays measuring circulating bone-specific ALP in mice models used in bone and mineral research.

Concepts: Bone, Liver, Alkaline phosphatase, Liver function tests, Chromatography, Small intestine, Mice, Offal

9

Rapalogs, inhibitors of mTORC1 (mammalian target of rapamycin complex 1), increase lifespan and delay age-related phenotypes in many species. However the molecular mechanisms have not been fully elucidated. We determined gene expression changes comparing 6 and 24-month old rats in the kidney, liver and skeletal muscle, and asked which of these changes were counter-regulated by a clinically-translatable (short-term and low-concentration) treatment, with a rapalog (RAD001). Surprisingly, RAD001 had a more pronounced effect on the kidney under this regimen in comparison to the liver or skeletal muscle. Histologic evaluation of kidneys revealed that the severity of chronic progressive nephropathy lesions was lower in kidneys from 24-month old rats treated with RAD001 compared with vehicle. In addition to other gene expression changes, c-Myc, which has been shown to regulate aging, was induced by aging in the kidney and counter-regulated by RAD001. RAD001 caused a decrease in c-Myc protein, which could be rescued by a proteasome inhibitor. These findings point to settings for use of mTORC1 inhibitors to treat age-related disorders, and highlight c-Myc regulation as one of the potential mechanisms by which mTORC1 inhibition is perturbing age-related phenotypes.

Concepts: DNA, Gene, Gene expression, Molecular biology, Glucose, Proteasome, Renin, Offal

7

As of 2009, anticoagulation with citrate was standard practice in continuous renal replacement therapy (CRRT) for critically ill patients at the University Medical Centre of Saarland, Germany. Partial hepatic metabolism of citrate means accumulation may occur during CRRT in critically ill patients with impaired liver function. The aim of this study was to evaluate the actual influence of hepatic function on citrate-associated complications during long-term CRRT.

Concepts: Medicine, Liver, Glycogen, Liver function tests, Derivative, Peritoneum, Liver disease, Offal

3

Autophagy is an intracellular degradation system activated, across species, by starvation. Although accumulating evidence has shown that mammalian autophagy is involved in pathogenesis of several modern diseases, its physiological role to combat starvation has not been fully clarified. In this study, we analysed starvation-induced gluconeogenesis and ketogenesis in mouse strains lacking autophagy in liver, skeletal muscle or kidney. Autophagy-deficiency in any tissue had no effect on gluconeogenesis during starvation. Though skeletal muscle- and kidney-specific autophagy-deficiency did not alter starvation-induced increases in blood ketone levels, liver-specific autophagy-deficiency significantly attenuated this effect. Interestingly, renal as well as hepatic expression of HMG-CoA synthase 2 increased with prolonged starvation. Furthermore, during starvation, mice lacking autophagy both in liver and kidney showed even lower blood ketone levels and physical activity than mice lacking autophagy only in liver. Starvation induced massive lipid droplet formation in extra-adipose tissues including liver and kidney, which was essential for ketogenesis. Moreover, this process was impaired in the autophagy-deficient liver and kidney. These findings demonstrate that hepatic and renal autophagy are essential for starvation-induced lipid droplet formation and subsequent ketogenesis and, ultimately, for maintaining systemic energy homeostasis. Our findings provide novel biological insights into adaptive mechanisms to combat starvation in mammals.

Concepts: Vitamin D, Metabolism, Glucose, Liver, Glycogen, Peritoneum, Renin, Offal

2

Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium/glucose co-transporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg, p.o.) treatment did not influence the impaired renal function; however, it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared with the vehicle group). Additionally, canagliflozin significantly increased cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial carbohydrate fermentation in the intestine. Analysis of the cecal microbiota showed that canagliflozin significantly altered microbiota composition in the renal failure mice. These results indicate that canagliflozin exerts intestinal effects that reduce the accumulation of uremic toxins including p-cresyl sulfate. Reduction of accumulated uremic toxins by canagliflozin could provide a potential therapeutic option in chronic kidney disease.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Dialysis, Bacteria, Gut flora, Offal

1

Abdominal compartment syndrome (ACS) sometimes occurs in critically ill patients following damage control surgery. The purpose of the present study was to develop a model of ACS and to evaluate its pathologic impact on liver, kidney, and lung morphology.

Concepts: Present, Time, Illness, English-language films, Modern history, Offal, Abdominal cavity, Compartment syndrome