Correction: Toivio et al. Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice. 2024, , 18.

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Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice.

Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases. However, little is known of how the fat source of these diets influences the intestinal barrier. Herein, we studied the impact of four-week feeding with KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) on paracellular permeability of the intestine to iohexol in healthy male C57BL/6J mice.

Adverse effects of an aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286), on inflamed rat colon.

Recently, we described local aldosterone production in the murine large intestine. Upregulated local aldosterone synthesis in different tissues has been linked with inflammatory conditions, which have been attenuated by the aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286). Therefore, we investigated the effect of inhibition of intestinal aldosterone synthesis on the development of intestinal inflammation.

Local aldosterone synthesis in the large intestine of mouse: An incubation study.

Objective: To investigate the regulation of local aldosterone synthesis by physiological stimulants in the murine gut.

Methods: Male mice were fed for 14 days with normal, high (1.6%) or low (0.

Renin-angiotensin system in intestinal inflammation-Angiotensin inhibitors to treat inflammatory bowel diseases?

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects.

Randomised Controlled Trial: Partial Hydrolysation of Casein Protein in Milk Decreases Gastrointestinal Symptoms in Subjects with Functional Gastrointestinal Disorders.

Unspecific gastrointestinal symptoms associated with milk consumption are common. In addition to lactose, also other components of milk may be involved. We studied whether the partial hydrolysation of milk proteins would affect gastrointestinal symptoms in subjects with functional gastrointestinal disorders.

Local ocular renin-angiotensin-aldosterone system: any connection with intraocular pressure? A comprehensive review.

The renin-angiotensin system (RAS) is one of the oldest and most extensively studied human peptide cascades, well-known for its role in regulating blood pressure. When aldosterone is included, RAAS is involved also in fluid and electrolyte homeostasis. There are two main axes of RAAS: (1) Angiotensin (1-7), angiotensin converting enzyme 2 and Mas receptor (ACE2-Ang(1-7)-MasR), (2) Angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor (ACE1-AngII-AT1R).

A Single Drop in the Eye - Effects on the Whole Body?

Introduction: Although the local adverse effects of ophthalmic drugs, including allergic reactions, are well recognized, less is known about the systemic side- effects of eye drops, especially during pregnancy, breast-feeding and early childhood. Ophthalmologists should also be aware of unusual, in some cases even life-threatening, effects of commonly used eye drops.

Conclusion: This brief review outlines the routes of systemic absorption and the kinetics of active components present in eye drops, and identifies the clinically relevant systemic adverse effects.

Many Faces of Renin-angiotensin System - Focus on Eye.

The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs.

Vascular Calcification, Vitamin K and Warfarin Therapy - Possible or Plausible Connection?

Atherosclerosis is a pathological process underpinning many cardiovascular diseases; it is the main cause of global mortality. Atherosclerosis is characterized by an invasion of inflammatory cells, accumulation of lipids and the formation of fatty streaks (plaques) which subsequently allow accumulation of calcium and other minerals leading to a disturbance in the vascular endothelium and its regulatory role in arterial function. Vascular calcification is a different process, stringently regulated mainly by local factors, in which osteoblast-like cells accumulate in the muscular layer of arteries ultimately taking on the physiological appearance of bone.

Local corticosterone production and angiotensin-I converting enzyme shedding in a mouse model of intestinal inflammation.

Aim: To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine.

Methods: Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water.

Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored.

[Renin-angiotensin system (RAS) in the bowel].

The significance of the renin-angiotensin system (RAS) in blood pressure regulation is indisputable. In addition to the heart and circulatory system, its components have recently been shown to be expressed also in the digestive tract, pancreas, brain and eyes, raising the idea that the significance of RAS for the functions of the body may be much more complex than currently thought. Its effects in the digestive tract could involve regulation of smooth muscle of the blood vessels and bowel, changes in permeability of the gut mucosa, or functioning as a digestive enzyme.

Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

Background: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature.

Low serum enterolactone concentration is associated with low colonic Lactobacillus-Enterococcus counts in men but is not affected by a synbiotic mixture in a randomised, placebo-controlled, double-blind, cross-over intervention study.

The aims of the present study were to assess the possible differences in faecal microbiota between men with a low serum enterolactone concentration and those with a high concentration, and to investigate the impact of a synbiotic mixture on serum enterolactone concentration in men with a low concentration. We compared faecal microbiota between ten men with the lowest serum enterolactone concentration and ten men with the highest concentration at recruitment (n 84). Furthermore, we carried out a randomised, double-blind, placebo-controlled, cross-over intervention study (6-week intervention periods and 4-week washout period) to investigate the impact of a synbiotic mixture (two Lactobacillus strains, one Bifidobacterium strain, one Propionibacterium strain and galacto-oligosaccharides (32 g/l)) on serum enterolactone concentration in fifty-two men who had a concentration < 20 nmol/l.

Antihypertensive effects of bioactive tripeptides-a random effects meta-analysis.

A meta-analysis of possible antihypertensive effects of small doses of bioactive tripeptides isoleucine-proline-proline and valine-proline-proline in commercial milk products or tablets was carried out. A random effects model was used on 19 randomized, placebo-controlled clinical intervention trials (published 1996-October 2010) consisting of about 1500 prehypertensive or mildly hypertensive subjects.The overall blood pressure lowering for systolic blood pressure was -4.

Plant sterols and casein-derived tripeptides attenuate blood pressure increase in spontaneously hypertensive rats.

In this study, we investigated the synergistic effects of plant sterols (PS) and casein-derived tripeptides on arterial tone and blood pressure in experimental hypertension. We hypothesized that PS and tripeptides could have positive, synergistic effects on the development of hypertension and endothelial dysfunction in young spontaneously hypertensive rats (SHR). Six-week-old male SHR were divided into 3 groups to receive milk products containing PS, or PS with tripeptides, or a control containing no active components for 8 weeks.

Flavonoids eupatorin and sinensetin present in Orthosiphon stamineus leaves inhibit inflammatory gene expression and STAT1 activation.

Cytokines and other inflammatory mediators, such as prostaglandin E₂ (PGE₂) and nitric oxide (NO) produced by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, activate and drive inflammation and therefore serve as targets for anti-inflammatory drug development. Orthosiphon stamineus is an indigenous medicinal plant of Southeast Asia that has been traditionally used in the treatment of rheumatoid arthritis, gout, and other inflammatory disorders. The present study investigated the anti-inflammatory properties of Orthosiphon stamineus leaf chloroform extract (CE), its flavonoid-containing CE fraction 2 (CF2), and the flavonoids eupatorin, eupatorin-5-methyl ether (TMF), and sinensetin, identified from the CF2.

A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and plant sterols has antihypertensive and cholesterol-lowering effects.

Lifestyle intervention is recommended as the primary treatment for mild hypertension and hypercholesterolemia. We studied the effects of a spread containing bioactive milk peptides IPP and VPP, as well as plant sterols, on cardiovascular risk factors in 104 hypertensive, hypercholesterolemic subjects in a randomised, placebo-controlled double-blind intervention. Middle-aged subjects consumed 20 g day⁻¹ of a spread containing 4.

Downregulation of Bradykinin type 2 receptor expression in cardiac endothelial cells during senescence.

Objectives: Bradykinin type 2 receptor (BK-2R) knockout mice develop microvascular dysfunction and cardiac hypertrophy. In aged human cardiac microvascular endothelium, dysfunction develops before heart failure symptoms. Since endothelial aging is an independent risk factor for cardiovascular disease, we aimed to clarify the role of kinin receptors in age-related endothelial senescence.

High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension.

Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to have antihypertensive effects in human subjects and to attenuate the development of hypertension in experimental models. The aim of the present study was to investigate the effect of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established hypertension, endothelial dysfunction and aortic gene expression. Male spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP) of 195 mmHg were given either active milk (tripeptides and plant sterols), milk or water ad libitum for 6 weeks.

Ile-Pro-Pro and Val-Pro-Pro tripeptide-containing milk product has acute blood pressure lowering effects in mildly hypertensive subjects.

Casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure (BP) in long-term clinical studies. Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro as well as plant sterols. Twenty-five subjects with untreated mild hypertension received in random order 250 g of study product (25 mg peptides and 2 g plant sterols) or placebo.

Local ocular renin-angiotensin system - a target for glaucoma therapy?

An active local intraocular renin-angiotensin system (RAS) has recently been shown to exist in the human eye, and evidence is now accumulating that antihypertensive drugs acting on RAS can also lower intraocular pressure. They seem also to work as neuroprotective agents against retinal ganglion cell loss in vivo; though no compounds are in ophthalmological use at present. Classically, the highly vasoconstrictive angiotensin II (Ang II) is the key peptide in the circulatory RAS.

Metabolism of ophthalmic timolol: new aspects of an old drug.

Glaucoma is a common eye disease that can cause irreversible blindness if not diagnosed and treated in the early stages of progression. This disease is often, albeit not always, associated with increased intraocular pressure, which is also the most important risk factor for glaucoma. Currently, the only treatment option of glaucoma is reduction of intraocular pressure.

Effects of flavonoids on prostaglandin E2 production and on COX-2 and mPGES-1 expressions in activated macrophages.

Prostaglandin E2 (PGE2) has a central role in inflammation and both cyclooxygenase-2 (COX-2) and prostaglandin E synthases are critical enzymes in its synthesis. In inflammation, bacterial products and cytokines enhance the expression of COX-2 and inducible microsomal prostaglandin E synthase-1 (mPGES-1) which are functionally coupled to result in increased PGE2 formation in macrophages and tissue cells. In the present study, we systematically investigated the effects of 26 naturally occurring flavonoids on PGE2 production and on COX-2 and mPGES-1 expression in activated macrophages.