Effect of insulin on small intestinal transit in normal mice is independent of blood glucose level

BACKGROUND: Insulin is the drug of choice in the management of diabetes mellitus (DM). About 76 % of diabetic patients suffer from gastrointestinal (GI) disorders. Therapy of DM with insulin primarily involves lowering of elevated blood glucose levels. Hence, on any organ in addition to insulin's effect, hypoglycaemic effect also prevails. A systematic study exploring the effect of insulin on small intestinal transit in normal laboratory animals is lacking. Hence, in the present study, the possible effect of insulin with or without associated hypoglycaemia on small intestinal transit in normal mice was examined. RESULTS: Insulin in all the doses tested (2 μ, 2 m and 2 U/kg) elicited a significant acceleration of SIT. The lower doses of insulin (2 μ and 2 m U/kg) produced significant acceleration of SIT and were associated with normal blood glucose levels. However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT that was associated with significant fall in blood glucose levels. Further, the 2 m and 2 U doses of insulin significantly elevated serum insulin and C-peptide levels. CONCLUSION: Insulin at the lowest dose produced an acceleratory effect on SIT that was independent of blood glucose and serum insulin levels in normal mice

Assessment of safety and efficacy of a dietary supplement KaraLiv™ in supporting liver health: a double-blind, parallel, placebo-controlled randomized clinical trial

Background: The liver is responsible for many critical functions within the body. If the liver becomes diseased or injured, loss of those critical functions can cause significant damage to the body. KaraLivTM is a novel herbal formulation which contains a blend of different herbal extract ingredients. The current study tested the safety and efficacy of KaraLivTM versus a placebo control in supporting liver function.Methods: The study is a randomized, double-blind, parallel, and placebo-controlled study. A total of 60 patients were divided into 2 groups of 30 each. One group was given KaraLivTM and the other group was given a placebo for a period of 56 days. Treatment results were assessed by evaluating the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and alkaline phosphatase (ALP) in both groups.Results: The herbal supplement KaraLivTM significantly supported healthy liver function compared to the placebo following the 56 days of treatment. The treatment (KaraLivTM) group showed a statistically significant improvement in assessed liver enzyme levels compared to the placebo group.Conclusions: The all-natural herbal supplement KaraLivTM is a safe and effective product that can significantly help support healthy liver function

A randomized, double-blind, parallel, placebo-controlled study to evaluate efficacy and safety of a synergistic multi-herbal extract blend KaraHeart™ in supporting healthy cholesterol levels

Background: Hyperlipidemia is a condition involving abnormally high levels of lipids in the blood. Hyperlipidemia is a major risk factor for cardiovascular diseases and refers to either high levels of triglycerides (TGL) or cholesterol. Herbal supplements have been used in the management of cholesterol levels in Ayurveda, a complete medical system originating in India. KaraHeart™ is a multi-herbal extract synergistic blend that may help in the management of healthy cholesterol levels. The current study tested the efficacy, tolerability, and safety of KaraHeart™ versus a placebo in the management of cholesterol levels of patients with mild hyperlipidemia.Methods: This was a randomized, double-blind, parallel, and placebo-controlled study. A total of 100 patients were divided into two groups. One group was given KaraHeart™ and the other group was given a placebo for 120 days. Treatment results were assessed by checking the lipid profile parameters such as total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and TGL.Results: The study found that the herbal supplement KaraHeart™ significantly reduced levels of LDL, VLDL, TGL, and total cholesterol, while increasing the levels of HDL in the blood. Additionally, the study concluded that KaraHeart™ was safe to use.Conclusions: KaraHeart™ was shown to be safe and effective in the management of cholesterol levels

A Dynamic Model for the Forward Curve

This paper develops and estimates a dynamic arbitrage-free model that models the current forward curve as the sum of (i) an unconditional component, (ii) a maturity-specific component and (iii) a date-specific component. The model combines features of the Preferred Habitat model, the Expectations Hypothesis and affine yield curve models. We show how to construct alternative parametric examples of the three components from a sum of exponential functions, verify that the resulting forward curves satisfy the Heath-Jarrow-Morton conditions, and derive the risk-neutral dynamics for the purpose of pricing interest rate derivatives. We select a model from alternative affine examples that are fitted to the Fama-Bliss Treasury data over an initial training period and use it to generate out-of-sample forecasts for forward rates and yields. For forecast horizons of 6-months or longer, the forecasts of this model significantly outperform forecasts from common benchmark models

Targeted microbubbles: a novel application for the treatment of kidney stones

Kidney stone disease is endemic. Extracorporeal shockwave lithotripsy was the first major technological breakthrough where focused shockwaves were used to fragment stones in the kidney or ureter. The shockwaves induced the formation of cavitation bubbles, whose collapse released energy at the stone, and the energy fragmented the kidney stones into pieces small enough to be passed spontaneously. Can the concept of microbubbles be used without the bulky machine? The logical progression was to manufacture these powerful microbubbles ex vivo and inject these bubbles directly into the collecting system. An external source can be used to induce cavitation once the microbubbles are at their target; the key is targeting these microbubbles to specifically bind to kidney stones. Two important observations have been established: (i) bisphosphonates attach to hydroxyapatite crystals with high affinity; and (ii) there is substantial hydroxyapatite in most kidney stones. The microbubbles can be equipped with bisphosphonate tags to specifically target kidney stones. These bubbles will preferentially bind to the stone and not surrounding tissue, reducing collateral damage. Ultrasound or another suitable form of energy is then applied causing the microbubbles to induce cavitation and fragment the stones. This can be used as an adjunct to ureteroscopy or percutaneous lithotripsy to aid in fragmentation. Randall's plaques, which also contain hydroxyapatite crystals, can also be targeted to pre-emptively destroy these stone precursors. Additionally, targeted microbubbles can aid in kidney stone diagnostics by virtue of being used as an adjunct to traditional imaging methods, especially useful in high-risk patient populations. This novel application of targeted microbubble technology not only represents the next frontier in minimally invasive stone surgery, but a platform technology for other areas of medicine

Assessment of safety and efficacy of Karallief® Easy ClimbTM, an herbal extract blend for supporting joint health: a double-blind, placebo-controlled, randomized clinical trial

Background: Osteoarthritis is common among the aging population worldwide. The current techniques to manage osteoarthritis focus on relieving pain and slowing the progression of the disease. Herbal or natural supplements have shown promise in achieving both these treatment goals. Two new proprietary herbal extract blends, Karallief® Easy ClimbTM (KEC) and herbal extracts with glucosamine (HEG), are combinations of several natural products shown to be effective in the treatment of knee osteoarthritis. The current study tested the efficacy and safety of KEC and HEG versus a placebo control.Methods: This is a randomized, double-blind and placebo-controlled study. A total of 120 patients were divided into 3 groups and were given KEC, HEG and Placebo in the ratio 1:1:1. Treatment results were assessed using the 30 second chair stand test, WOMAC test, knee flexion test and joint space measurement using X-rays of the knee joint.Results: The study found that the herbal supplements HEG and KEC significantly reduced osteoarthritis-related knee pain and increased joint mobility and were safe to use during 120 days of treatment. Both supplements resulted in an improvement in the 30 second chair stand test results, WOMAC pain scores, knee flexion, and joint space width as measured by X-ray, as compared to the placebo.Conclusions: Natural supplements such as HEG and KEC improve knee osteoarthritis symptoms and can be a safe and effective treatment option for patients with osteoarthritis

mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft

<p>Abstract</p> <p>Background</p> <p>Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA) levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted ρ⁰counterparts grown in culture and as tumor xenografts in immune-deficient mice.</p> <p>Results</p> <p>Cultured A549 ρ⁰cells were respiration-deficient and showed enhanced levels of transcripts relevant to metal homeostasis, initiation of the epithelial-mesenchymal transition, and glucuronidation pathways. Several well-established HIF-regulated transcripts showed increased or decreased abundance relative to the parental cell line. Furthermore, growth in culture versus xenograft has a significantly greater influence on expression profiles, including transcripts involved in mitochondrial structure and both aerobic and anaerobic energy metabolism. However, both <it>in vitro </it>and <it>in vivo</it>, mtDNA levels explained the majority of the variance observed in the expression of transcripts in glucuronidation, tRNA synthetase, and immune surveillance related pathways. mtDNA levels in A549 xenografts also affected the expression of genes, such as <it>AMACR </it>and <it>PHYH</it>, involved in peroxisomal lipid metabolic pathways.</p> <p>Conclusion</p> <p>We have identified mtDNA-dependent gene expression profiles that are shared in cultured cells and in xenografts. These profiles indicate that mtDNA-depleted cells could provide informative model systems for the testing the efficacy of select classes of therapeutics, such as anti-angiogenesis agents. Furthermore, mtDNA-depleted cells grown culture and in xenografts provide a powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.</p

Synthesis, spectral characterization, anti-bacterial, cytotoxic evaluation and docking studies of new urea and thiourea derivatives

Isoniazid is one of the main API’s used in the combination treatment of tuberculosis recommended by the WHO. Urea and its derivatives are an important class of heterocyclic compounds that possess a wide range of therapeutic and pharmacological properties, while thiourea is an organosulphur compound in that it resembles urea except that the atom oxygen has been replaced by a Sulphur atom, but the properties of urea and thiourea are significantly different. The current work concerns the synthesis of a new class of urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates in the presence of trimethylamine. The IR and NMR spectral data were performed for the urea and thiourea derivatives of the compounds [(3c &amp; 3f) &amp; (3d &amp; 3e)], respectively. Molecular docking studies of the compounds (3a-h) revealed the binding mode involved in the active site of DNA gyrase. The synthesized urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates were tested for their antibacterial activity against gram-positive and gram-negative bacteria using the “disc diffusion method”. Of all compounds tested, the urea derivatives (3a &amp;3d), the thiourea derivatives (3e &amp; 3g) showed more potent activity than the other compounds. The MTT assay revealed concentration dependent cytotoxic effects over a concentration range 25-200 µg/mL

Human and great ape red blood cells differ in plasmalogen levels and composition

<p>Abstract</p> <p>Background</p> <p>Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease.</p> <p>Results</p> <p>In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the <it>sn</it>-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the <it>sn</it>-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues.</p> <p>Conclusion</p> <p>We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross-species differences in tissue plasmalogen levels could influence organ functions and processes ranging from cognition to reproduction to aging.</p