https://escholarship.org/content/qt5h57v276/qt5h57v276.pdf?t=pqtny0

High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children.

Haptoglobin is an acute phase protein that scavenges haemoglobin in the event of intravascular or extravascular haemolysis. The protein exists in humans as three main phenotypes, Hp1-1, Hp2-2 and Hp2-1. Accumulated data on the protein's function has established its strong association with diseases that have inflammatory causes. These include parasitic (malaria), infectious (HIV, tuberculosis) and non-infectious diseases (diabetes, cardiovascular disease and obesity) among others. Phenotype-dependent poor disease outcomes have been linked with the Hp2-2 phenotype. The present review brings this association into perspective by looking at the functions of the protein and how defects in these functions associated with the Hp2 allele affect disease outcome. A model is provided to explain the mechanism, which appears to be largely immunomodulatory.

Haptoglobin, inflammation and disease.

Here, we review a novel concept namely the compensatory immune-regulatory reflex system (CIRS) as applied to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). There is evidence that a substantial subset of individuals with MDD and BD exhibit an activation of the immune-inflammatory response system (IRS), as indicated by an increased production of macrophagic M1 and T helper (Th)-1 pro-inflammatory cytokines, interleukin (IL)-6 trans-signaling, positive acute phase proteins (APPs), and complement factors. These immune aberrations appear to be evident during the course of major affective episodes of either depressive or (hypo) manic polarity. Here, we review (a) the current state of the art of CIRS functions in both mood disorders and (b) the possible role of CIRS-related biomarkers for the understanding of affective disorders within the framework of precision psychiatry that could also provide novel drug targets for both MDD and BD. CIRS-related abnormalities in mood disorders include elevated Th-2 and T regulatory (Treg) activities with increased IL-4 and IL-10 production, classical IL-6 signaling, increased levels of sIL-1R antagonist (sIL-1RA), soluble IL-2 (sIL-2R) and tumor necrosis factor–α- receptors, and positive APPs, including haptoglobin, hemopexin, α1-acid glycoprotein, α1-antitrypsin, and ceruloplasmin. It is concluded that CIRS is involved in MDD and BD by regulating the primary immune-inflammatory response, thereby contributing to spontaneous and antidepressant-promoted recovery from the acute phase of illness. Signs of activated IRS and CIRS pathways are observed in the remitted phases of both disorders indicating that there is no return to the original homeostasis after an acute episode, while later episodes of mood disorders are characterized by sensitized IRS and CIRS responses. New z-unit weighted composite biomarker scores are proposed, which reflect different aspects of IRS versus CIRS activation and may be used to estimate different IRS/CIRS activity ratios in mood and other neuroimmune disorders.

The Compensatory Immune-Regulatory Reflex System (CIRS) in Depression and Bipolar Disorder

https://escholarship.org/content/qt0vk0d612/qt0vk0d612.pdf?t=ot10p3

Fetal Exposure to Maternal Depressive Symptoms Is Associated With Cortical Thickness in Late Childhood

Background: Patients with obesity, diabetes, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. Methods: We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m 2 ), and stage 2-4 CKD (estimated glomerular filtration rate [eGFR] 15-90 mL/min/1.73 m 2 with persistent proteinuria). Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria. Results: Seven subjects randomized to exercise and 4 control subjects completed the study. Exercise training resulted in an increase in exercise duration during treadmill testing, which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria. Exercise did not alter GFR, hemoglobin, glycated hemoglobin, serum lipids, or Creactive protein (CRP). Caloric intake and body weight and composition also did not change with exercise training. Conclusion: Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits. A large-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD is planned.

/pdf/aerobic-exercise-in-obese-diabetic-patients-with-chronic-3fyjm4f3cv.pdf

Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study

SPECIFIC AIMSCollagen turnover and cell migration are regarded as essential processes of arterial restructuring but components and regulatory mechanisms of arterial restructuring are still unclear....

Acute-phase protein haptoglobin is a cell migration factor involved in arterial restructuring.

The present invention provides compounds and methods for the treatment and prophylaxis of ischemia reperfusion injury. In particular the invention provides compounds which function to suppress Toll-like Receptor 2 biological function or expression.

Use of tlr-2 antagonists for treatment of reperfusion injury and tissue damage

Since it was first described in 1990, subintimal angioplasty (SIA) has proven to be a valuable alternative for bypass surgery in patients with atheroocclusive disease of the superficial femoral artery (SFA).1 In this minimally invasive technique, a guidewire is intentionally placed between the intima and the media to create a new track along the vessel wall, bypassing the atherosclerotic occlusion.2 However, to our knowledge, the exact route of this subintimal track has never been confirmed with histopathology.

There have been debates about the exact route of the guidewire during this procedure. Bolia et al2 were the first to report on this technique and emphasized that during subintimal passage, the guidewire does not pass the medial layer. On the other hand, Reekers et al3 observed that large, extensive, medial calcifications often result in the inability to perform this technique and concluded that the passage through the medial layer is necessary. Reekers et al, therefore, preferred to call this technique percutaneous intentional extraluminal revascularization.

In this case report, we present a patient from whom an endarterectomy specimen of an occluded SFA was obtained 2 months after an SIA procedure, which gave the unique opportunity to study the exact route of the subintimal track using histopathology.

### Case

A …

Images and Case Reports in Interventional Cardiology Subintimal Angioplasty Track of the Superficial Femoral Artery A Histological Analysis

The present invention relates to a method of predicting the risk of a subject developing a cardiovascular event, comprising determining the presence of a biomarker that is indicative of the risk of developing a cardiovascular event in an exosome sample from the subject. The exosomes are suitably isolated from a body fluid selected from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, saliva, in particular serum. Alternatively, the exosomes are present in a body fluid, in particular serum. The biomarker is selected- from the proteins Vitronectin, Serpin F2, CD14, Cystatin C, Plasminogen, Nidogen 2, Serpin Gl or any combination of two or more of these proteins. The invention further relates to a method of diagnosing the occurrence of acute coronary syndrome in a subject, comprising determining the presence of a biomarker that is indicative of the occurrence of acute coronary syndrome in an exosome sample from the subject. In this method the biomarker is selected from Serpin F2, CD14, Cystatin C or combinations thereof.

Exosomal biomarkers for predicting cardiovascular events

Composition and method for treatment of reperfusion injury and tissue damage

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