The effect of physical exercise on reverse cholesterol transport

High-density lipoproteins (HDL) are recognized for their role in coronary artery disease (CAD) risk reduction. Plasma HDL plays a pivotal role in the reverse cholesterol transport (RCT) process. Physical exercise is well recognized as a modality that affects HDL metabolism. The purpose of this discussion is to describe the effects of physical exercise on RCT.     

Treatment of multidrug-resistant pulmonary tuberculosis with delamanid based on Japanese guideline recommendations

BackgroundIn Japan, a new anti-tuberculous drug, delamanid, was recognized as the drug of choice to treat multi-drug resistant pulmonary tuberculosis in July 2014.MethodsWe treated 28 cases of multidrug-resistant tuberculosis (MDR-TB) and three cases of extensively drug-resistant tuberculosis (XDR-TB) with delamanid from July 2014 to June 2018 at our hospital.ResultsThere were 21 men and 10 women, with the mean age of 48 and 37 years, respectively. We used an average of 4.4 sensitive anti-tuberculous drugs for the MDR-TB cases and 4.7 for the XDR-TB cases with delamanid. We used linezolid in 19 of 31 cases, although it has not been recognized as an anti-tuberculous drug in Japan. On electrocardiography, QTc prolongation of more than 450 ms was seen in two cases (6.4%), but they were asymptomatic, thus the treatment with delamanid could be continued. In 10 cases, surgical resection was performed.We completed the treatment in 20 cases and continued the treatment in seven cases; however, the treatment was discontinued in four cases because of side effects. In all cases, the sputum cultures were negative.ConclusionsDelamanid is a relatively safe drug with few side effects. However, some patients could not continue it because of difficulty of use in combination, therefore delamanid should be prescribed considering the side effects of all therapies in the regimen.     

Systemic effects of chronic obstructive pulmonary disease: what we know and what we don't know (but should)

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. The latter is likely to contribute significantly to the pathobiology of numerous extrapulmonary effects of the disease--the so-called systemic effects of COPD. The clinical relevance of these systemic effects has been recently recognized; however, many important questions about its pathophysiology remain unanswered. This article reviews what is known about it and, more importantly, highlights what is not (but should be) known in order to stimulate research in this area, in the hope that a better understanding of this field may lead to better treatment options for patients with COPD.     

Bisphosphonates and Osteonecrosis of the Jaws: A Review of Clinical Features and the Drug Effect on Oral Soft Tissues

The beneficial effects of the nitrogen-containing bisphosphonate drugs have been clearly defined, especially for the treatment for osteoporosis, metastatic or primary bone malignancies, and some rare bone diseases. The adverse effects of these drugs on oral hard and soft tissues are significant and recognized with increasing frequency. The clinical, radiographic, and histopathologic features of osteonecrosis of the jaws (ONJ) are well characterized; the effects of bisphosphonates on oral soft tissues are an emerging area of study. This review will provide an overview of ONJ from a clinical perspective and also discuss recent findings related to bisphosphonate-induced soft tissue pathology.     

Vitamin D deficiency: Implications for acute care in the elderly and in patients with chronic illness

There is evidence that the vast majority of hospitalized patients have vitamin D deficiency. Vitamin D deficiency is a poorly recognized pandemic with evidence to indicate inadequate testing and monitoring of response to treatment in high‐risk populations. Vitamin D receptors are ubiquitous in the human body and while the endocrine effects of vitamin D are well recognized, the autocrine and paracrine effects of this steroid hormone are less well appreciated. These functions include antimicrobial and immunomodulation effects as well benefits on cardiovascular health, autoimmune disease, cancer and metabolism. Vitamin D deficiency increases mortality and even a modest amount of vitamin D may enhance longevity. Emerging evidence suggests that a vitamin D replete state carries significant health benefits in acute illness. In this review, we discuss the role of vitamin D deficiency and potential benefits in treating this deficiency focusing on the implications for managing acute illness in elderly patients and those with an underlying chronic illness. Geriatr Gerontol Int 2011; 11: 395–407.     

Central and peripheral testosterone effects in men with heart failure: An approach for cardiovascular research

Heart failure (HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action. The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures. Central effects include influences on cardiomyocytes and electrophysiology. Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis. Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.     

Hepatitis C virus and the lung: implications for therapy

Hepatitis C virus (HCV) infection is a chronic blood-borne disease that affects > 4,000,000 individuals in the United States. The majority of individuals with HVC infection acquire a chronic hepatitis that predisposes them to the complications of cirrhosis and hepatoma. Chronic HCV infection is, however, associated with multiple extrahepatic manifestations as well, including recently recognized effects on the lung. These include primary effects on lung function, as well as secondary effects in the settings of progressive liver disease and drug treatment for HCV. In this article, we discuss the emerging clinical data that support a role for HCV infection in lung disease, describe the multiple pulmonary manifestations of this viral infection, and outline the therapies available for specific pulmonary complications of chronic HCV infection.     

Time course of vagal effects studied in clinical electrocardiograms

We consider the transient effects of brief bursts of vagal stimulationon cardiac excitation and conduction as manifested in the clinicalelectrocardiogram. We hypothesize that such vagal effects maybe more frequent than commonly recognized and that they mayaccount for some types of arrhythmias that are commonly ascribedto other mechanisms. We first briefly review the direct chronotropicand dromotropic effects of brief vagal stimulus bursts in animalsand man. We next consider the effects of brief vagal burstson heart period in various arrhythmias in man, particularlyventriculophasic sinus arrhythmia with various degrees of A–Vblock, and various patterns of A–V dissociation. We illustratethese points with numerous clinical ECGs from our patient population,and with other cases from the literature. We next consider theeffects of brief vagal bursts on A–V conduction time,and illustrate this with clinical cases of: (a) prolongationof A–V conduction after premature beats, (b) ‘supernormal’A–V conduction, (c) Wenckebach periodicities, and (d)alternation of A–V conduction times. We review the evidencethat brief vagal bursts are generated in vivo, and are a naturallyoccurring reflex phenomenon. We therefore suggest that suchbrief vagal effects should perhaps be considered more commonlywhen ascribing mechanisms to some complex and often difficultto interpret arrhythmias.     

Modes of action of aspirin-like drugs: Salicylates inhibit Erk activation and integrin-dependent neutrophil adhesion

The anti-inflammatory effects of high-dose salicylates are well recognized, incompletely understood and unlikely due entirely to cyclooxygenase (COX) inhibition. We have previously reported a role for activation of the kinase Erk in CD11b/CD18 integrin-dependent adhesiveness of human neutrophils, a critical step in inflammation. We now report the effects of salicylates on neutrophil Erk and adhesion. Exposure of neutrophils to aspirin or sodium salicylate (poor COX inhibitor) inhibited Erk activity and adhesiveness of formylmethionyl-leucyl-phenylalanine- and arachidonic acid-stimulated neutrophils, consistent with anti-inflammation but not COX inhibition (IC₅₀s = 1–8 mM). In contrast, indomethacin blocked neither Erk nor adhesion. Inhibition of Mek (proximal activator of Erk) also blocked stimulation of Erk and adhesion by formylmethionyl-leucyl-phenylalanineand arachidonic acid. Salicylate inhibition of Erk was independent of protein kinase A activation and generation of extracellular adenosine. These data are consistent with a role for Erk in stimulated neutrophil adhesion, and suggest that anti-inflammatory effects of salicylates may be mediated via inhibition of Erk signaling required for integrin-mediated responses.     

Modulating atherosclerosis through inhibition or blockade of angiotensin

Angiotensin-convertng enzyme (ACE) inhibitors are well recognized for their benefits in treating hypertension and congestive heart failure and preventing postmyocardial infarction heart failure or left ventricular (LV) dysfunction. Recently, blockade of the angiotensin II type 1 (AT1) receptor was shown to reduce cardiovascular events in hypertensive subjects with LV hypertrophy. Several lines of evidence are now converging to show that ACE inhibitors may affect the atherosclerotic process itself. Emerging clinical data indicate that angiotensin-receptor blockers (ARBs) may possibly modulate atherosclerosis as well. The antiatherogenic properties of ACE inhibitors and ARBs may derive from inhibition or blockade of angiotensin II, now recognized as an agent that increases oxidative stress.Angiotensin-converting enzyme inhibition and angiotensin-receptor blockade also increase endothelial nitric oxide formation, which improves endothelial function. In contrast to the effects of ARBs, the vascular effects of ACE inhibitors may, in part, be mediated by an increase in bradykinin. This article reviews some of the biologic mechanisms whereby ACE inhibitors and ARBs may modulate atherosclerosis.     

Clinical considerations for the management of residual diabetes following bariatric surgery

Residual diabetes following bariatric surgery is increasingly recognized despite initial weight loss. It occurs more commonly following banding and sleeve gastrectomy procedures than with gastric bypass, is associated with long duration and advanced stages of diabetes and is exacerbated by weight regain. Long-term diabetes management following various gastric restrictive surgery (i.e. lap banding) requires targeting weight loss, insulin resistance and insulin secretion defects with antidiabetic agents that have weight negative or neutral effects. In contrast, re-emergence of hyperglycaemia following gastric bypass may require targeting β-cell failure with insulin analogues. Revisional bariatric surgery is also a consideration. On the basis of our experience, we propose a clinical approach for long-term management of diabetes following various bariatric procedures in the presence and absence of weight regain that is based on recognized pathophysiological effects of these procedures on diabetes remission.     

Distinct patterns of peripheral HIV-1-specific interferon- gamma responses in exposed HIV-1-seronegative individuals

It is unclear how human immunodeficiency virus (HIV) type 1-specific immune responses in exposed seronegative (ESN) individuals differ from those in HIV-1-infected subjects. By use of overlapping peptides spanning Gag, Tat, Nef, Vif, Vpr, and Vpu, peripheral blood mononuclear cells from ESN individuals, their seropositive (SP) partners, and unexposed seronegative control subjects were screened for interferon- gamma production. Responses were more frequent (95.7% vs. 20%), of a higher magnitude (9-fold), and of wider breadth (median number of peptides recognized, 18 vs. 2.5) in SP than in ESN individuals. Peptides recognized by ESN individuals were less frequently recognized by their SP partners. SP subjects infrequently recognized peptides from Vif, and such responses were subdominant; among ESN individuals, this HIV-1 protein was most frequently recognized. Immunodominant peptides recognized by SP subjects tended to be from relatively conserved regions, whereas peptides recognized by ESN individuals were associated with slow disease progression.     

Gender Dimorphisms in Progenitor and Stem Cell Function in Cardiovascular Disease

Differences in cardiovascular disease outcomes between men and women have long been recognized and attributed, in part, to gender and sex steroids. Gender dimorphisms also exist with respect to the roles of progenitor and stem cells in post-ischemic myocardial and endothelial repair and regeneration. Understanding how these cells are influenced by donor gender and the recipient hormonal milieu may enable researchers to further account for the gender-related disparities in clinical outcomes as well as utilize the beneficial effects of these hormones to optimize transplanted cell function and survival. This review discusses (1) the cardiovascular effects of sex steroids (specifically estradiol and testosterone); (2) the therapeutic potentials of endothelial progenitor cells, mesenchymal stem cells, and embryonic stem cells; and (3) the direct effect of sex steroids on these cell types.     

Successful treatment with rituximab of an infant with refractory autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is a rare disease in infants, for which steroids are recognized as a first-line therapy for patients. Rituximab, a humanized monoclonal antibody raised against CD20, has been used in the treatment of autoimmune diseases, including AIHA, in adults and children. Due to limited follow-up study of the use of rituximab in the treatment for AIHA, its long-term efficacy, adverse effects, and immunological reconstitution of B cells have not been fully evaluated in infants. Here, we report a 3-month-old female patient with refractory AIHA, who was successfully treated with rituximab. Hemolytic anemia improved rapidly, and there were no severe adverse effects caused by rituximab. After 4.5 months following rituximab treatment, peripheral B cells were gradually reconstituted and required no intravenous immunoglobulin replacement thereafter. The patient has remained disease-free for more than 30 months without any additional treatment. This case suggests that rituximab may be a valuable therapeutic option, given its efficacy and minimal adverse effects in infants with therapy-resistant AIHA.     

Basic evaluation of older persons with hypertension

To achieve the objectives of the baseline evaluation of older persons with hypertension, age-related changes that affect blood pressure measurement, assessment of target-organ effects, cardiovascular disease risk, and comorbidities need to be recognized. Careful attention to recommended procedures for blood pressure measurement, conducting a history, performing a physical examination, and using laboratory tests will allow the physician to confirm the presence of hypertension; to assess its effects on target organs; to determine cardiovascular risk status relating to other factors; and to identify other diseases, laboratory abnormalities, or psychosocial factors that may affect subsequent management.     

New insights into the renin-angiotensin system and hypertensive renal disease

The role of the renin-angiotensin system in hypertension and end organ damage has long been recognized. Recent advances in genetic models and newly available pharmacologic tools have allowed dissection of the mechanisms of actions of the renin-angiotensin system in hypertensive kidney disease. The newly cloned AT2 receptor is now recognized to oppose many of the AT1 receptor’s actions. The renin-angiotensin system is now recognized to be linked to induction of plasminogen activator inhibitor-1 (PAI-1), possibly via the AT4 receptor, thus promoting both thrombosis and fibrosis. Interactions of the reninangiotensin system with aldosterone and bradykinin may have impact on both blood pressure and tissue injury. The effects of angiotensin 1 converting enzyme inhibitors versus those of the newly available AT1 receptor antagonists on blood pressure and organ damage are undergoing evaluation in clinical trials. Finally, polymorphisms of genes relevant to the renin-angiotensin system appear to affect response to treatment, although this effect varies in different populations.     

Faut-il avoir peur des corticoïdes inhalés chez l’enfant ?

Inhaled corticosteroids are recognized as the most effective anti-inflammatory therapy in asthmatic children. Concerns have been raised about potential systemic effects. Systemic availability of inhaled corticosteroids is influenced by many factors such as potency and the pharmacodynamic properties of the molecule, delivery methods, or patient characteristics. Few studies take into account these parameters. Available studies suggest that systemic effects are absent or negligible for doses up to 500 μg/day of beclomethasone or equivalent. Significant biological modifications are observed for higher doses concerning the hypothalamic-pituitary-adrenal axis and bone metabolism. Clinical relevance of these modifications remains unknown. No definite growth retardation could be demonstrated, even for high doses of inhaled corticosteroids.     

Influenza D Virus: A Review and Update of Its Role in Bovine Respiratory Syndrome

Bovine respiratory disease (BRD) is one of the most prevalent, deadly, and costly diseases in young cattle. BRD has been recognized as a multifactorial disease caused mainly by viruses (bovine herpesvirus, BVDV, parainfluenza-3 virus, respiratory syncytial virus, and bovine coronavirus) and bacteria (Mycoplasma bovis, Pasteurella multocida, Mannheimia haemolytica and Histophilus somni). However, other microorganisms have been recognized to cause BRD. Influenza D virus (IDV) is a novel RNA pathogen belonging to the family Orthomyxoviridae, first discovered in 2011. It is distributed worldwide in cattle, the main reservoir. IDV has been demonstrated to play a role in BRD, with proven ability to cause respiratory disease, a high transmission rate, and potentiate the effects of other pathogens. The transmission mechanisms of this virus are by direct contact and by aerosol route over short distances. IDV causes lesions in the upper respiratory tract of calves and can also replicate in the lower respiratory tract and cause pneumonia. There is currently no commercial vaccine or specific treatment for IDV. It should be noted that IDV has zoonotic potential and could be a major public health concern if there is a drastic change in its pathogenicity to humans. This review summarizes current knowledge regarding IDV structure, pathogenesis, clinical significance, and epidemiology.     

Hypopituitarism due to sports related head trauma and the effects of growth hormone replacement in retired amateur boxers

Traumatic brain injury (TBI) has been recently recognized as a leading cause of pituitary dysfunction. Current data clearly demonstrated that sports related head trauma due to boxing, kickboxing, and soccer might results in pituitary hormone deficiencies, isolated growth hormone (GH) deficiency in particular. In the present report physiologic dose GH replacement therapy (GHRT) was performed in two GH deficient retired amateur boxers for the first time. The boxers received recombinant GH for 6 months. After 6 months of GHRT there were substantial improvements, but not complete normalization, in the body composition parameters, lipid profiles and quality of life scores in both boxers. These preliminary results suggest that GHRT may have beneficial effects in retired boxers with severe isolated GH deficiency due to sports related head trauma. But more data with higher number of boxers and longer GHRT duration are warranted.     

An Analysis of Kikuchi Lines Observed with a RHEED Apparatus for a TiO2-Terminated SrTiO3 (001) Crystal

In this study, electron diffraction patterns observed under high vacuum conditions for an SrTiO₃ surface were interpreted in detail while paying special attention to the features of inelastic effects. The surface of the SrTiO₂ was carefully prepared to enforce its termination with single domains of TiO₂ layers at the top. The inelastic patterns were interpreted using analytical models. Two types of Kikuchi lines are recognized in this paper: those which can be described with the Bragg law and those which appear due to surface wave resonance effects. However, we also discuss that there exists a formal connection between the two types of the Kikuchi lines observed.