Lipids,Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

Background

Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.

Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes

Guillain-Barré syndrome (GBS), characterised by limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases, and Campylobacter jejuni is the most frequent antecedent pathogen. GBS subsequent to C jejuni enteritis is associated with a severe, pure motor axonal variant and IgG antibodies against GM1, GM1b, GD1a, or GalNAc-GDla, gangliosides expressed in human peripheral nerves. Lipopolysaccharides of C jejuni isolated from GBS patients have ganglioside-like epitopes. Cytomegalovirus is the most common viral antecedent infection. Patients with demyelinating GBS who have had a recent CMV infection have severe sensory deficits and anti-GM2 IgM antibody. CMV-infected fibroblasts express the GM2 epitope. Fisher syndrome (FS), characterised by ophthalmoplegia, ataxia, and areflexia, is a GBS variant associated with anti-GQ1b IgG antibody. GQ1b is enriched in the cranial nerves that innervate the extraocular muscles. Some patients develop FS after C jejuni infection, and the lipopolysaccharide present bears the GQ1b epitope. Molecular mimicry is a possible cause of GBS and FS.     

Cardioprotective and antiarrhythmic effects ofβ-blockers,propranolol, bisoprolol,and nipradilol in a canine model of regional ischemia

Summary Cardioprotective and antiarrhythmic effects of three-blockers with different pharmacological properties were investigated in 33 anesthetized dogs with a 2-h coronary occlusion. Dogs were divided into 4 groups and received physiological saline or one of the following drugs using a 10-min infusion at 25 min before the occlusion: saline or control (n=12), propranolol (0.3 mg/kg,n=7), bisoprolol (0.05 mg/kg,n=7), and nipradilol (0.2 mg/kg,n=7) groups.Blood pressure did not significantly differ among the 4 experimental groups throughout the entire observation period. On the contrary, the postocclusion change (fall) in heart rate from the preocclusion value was significantly (P<0.05–0.01) greater in the drug-treated groups than in the control group. Each of the-blockers effectively prevented the development of ventricular arrhythmias associated with the 2-h coronary occlusion. In terms of assessing a cardioprotective effect, the respiratory control index and rate of oxygen consumption in State III in mitochondria, and lysosomal enzyme activities (N-acetyl--glucosaminidase or-glucuronidase) in myocardial tissues, all prepared from both ischemic and non-ischemic areas, were measured using the respective, established methods. The 2-h coronary occlusion induced a mitochondrial dysfunction and leakage of lysosomal enzymes in the control group, whereas each-blocker significantly (P < 0.05–0.01) protected mitochondria against ischemia and prevented the lysosomal enzyme leakage. The results indicate that the antiarrhythmic effects of-blockers on ischemic myocardium are, at least in part, due to their cardioprotective action, and these effects appear to be unrelated to the ancillary pharmacological properties of these drugs.     

Treatment of Crohn’s disease of inflammatory,stenotic, and fistulizing phenotypes

Opinion statement The heterogeneous nature of Crohn’s disease (CD) is reflected in the diversity of treatment options available for individual patients. The stratification of CD patients into more homogeneous groups based on disease location and disease behavior may provide clinicians with a more focused approach to therapeutic decision-making. Uncomplicated disease behaviors are typically treated medically. When complications arise and patterns of disease become more aggressive, combined medical and surgical approaches are often necessary and yield favorable results. The surgical management of CD can be as complex as the disease itself, and should involve a surgeon who professes a special expertise in inflammatory bowel disease. Progress in our understanding of the role of the interaction between the environment and the immune system in disease development has led to major advancements in the area of CD therapeutics. Current therapies target the various elements of the inflammatory cascade implicated in the pathogenesis of CD. The anti-inflammatory properties of the pharmacologic therapies presented in this review vary from actions that are extremely broad to those that are cellular or cytokine specific. Maximizing the efficacy of CD-directed therapies while minimizing their toxicity remains the principal objective in developing management strategies for CD patients. Maintaining good quality of life and maximizing adherence to therapies are also important considerations. Despite the various therapeutic options available for CD patients, chosen therapies should be based on the overall treatment goal for individual patients. Therapeutics can be broadly categorized as induction therapies (goal to treat active disease) and maintenance therapies (goal to prevent relapse of disease).     

Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-α, TGF-β, bFGF and Vimentin) in cultured and transplanted rat islets

Aims/hypothesis. The vascularisation of newly transplanted islets originates from the recipients. Because islets transplanted into a diabetic do less well than those transplanted into a euglycaemic environment, we examined the hypothesis that gene expression of angiogenic factors in grafts is delayed in diabetes. These factors include hepatocyte growth factor (HGF) and its receptor c-MET, and urokinase plasminogen activator (uPA) and its receptor uPAR, basic fibroblast growth factor (bFGF), TGF-α and TGFβ-1.¶Methods. Isolated rat islets were studied in vitro under normoxic and hypoxic culture conditions and gene expression was determined with semi-quantitative multiplex RT-PCR. We found that HGF but not c-MET expression was induced by hypoxia in vitro. Using syngeneic Lewis rats, gene expression was also studied in grafts on days 1, 3, 5, 7 and 14 after transplantation.¶Results. In grafts of normoglycaemic rats, HGF expression was enhanced on day 3 and maintained whereas expression of c-MET fell and remained down until day 14. Expression of uPA was up at day 3 and remained high; expression of uPAR was also up at day 3 but then fell to control levels at day 14. Expression of bFGF, TGF-α and TGFβ-1 persisted throughout. Vimentin, a marker of fibroblasts, had increased expression at day 1 which was further enhanced in subsequent days. In the grafts of diabetic recipients the expression of HGF, uPA and uPAR were delayed, being clearly expressed at day 5 rather than day 3. Vimentin expression was similarly delayed.¶Conclusion/interpretation. This apparent delay in angiogenesis provides a potential mechanism for the less favourable outcomes of islets transplanted into diabetic recipients. [Diabetologia (2000) 43: 763–772]     

Imaging and pathological characteristics,treatment, and prognosis of pulmonary sequestration—A retrospective study of 13 cases

Objective

This study aimed to summarize and analyze the characteristics of pulmonary sequestration to improve our understanding of this disease.

Methods

Between January 2019 and April 2023, the clinical data of 13 patients with pulmonary sequestration underwent surgical treatment at the First Affiliated Hospital of Gannan Medical University.

Results

The male-to-female ratio was 4:9, the age was 0.5 to 60 years, and the average age was 38 ± 19 years. There were 10 and 3 cases of intralobar and extralobar pulmonary sequestration, respectively. Chest enhanced computed tomography (CT) and three-dimensional vascular reconstruction showed that the abnormal blood vessels were derived from the descending thoracic aorta in nine cases and from other blood vessels in four cases. Three patients underwent thoracoscopic lobectomy, two underwent thoracoscopic segmentectomy, and eight underwent thoracoscopic wedge resection. All the patients successfully completed the surgery and were discharged postoperatively.

Conclusions

Some patients with pulmonary sequestration exhibit no obvious symptoms. Patients with clinical symptoms are easily confused for pneumonia, bronchial cysts, lung abscesses, and lung tumors; therefore, patients with pulmonary sequestration are prone to missed diagnosis and misdiagnosis. Currently, enhanced chest CT combined with three-dimensional vascular reconstruction can accurately show the course, branches, and relationship with the mass of the feeding artery. Routine pathological examination is helpful to further clarify the diagnosis of pulmonary sequestration. Minimally invasive thoracoscopic surgery is the preferred treatment for patients with pulmonary sequestration. Surgical resection is safe and feasible, and satisfactory results are typically obtained.     

Occurrence and morphology of some predatory fungi, amoebicidal, rotifericidal and nematodicidal, in the surface waters of Białystok region

Studies concerned the occurrence of some predatory fungi in the surface waters: springs, rivers, lakes and ponds of Bia?ystok region, collected in years 1999-2002. The following species of predatory fungi, amoebicidal, rotifericidal and nematodicidal were found: Arthrobotrys oligospora Fresenius, Zoophagus insidians Somlnestorff, Somnuerstorffia spinosa Arnaudov, Dactylaria brochopaga Drechsler, Euryancale sacciospora Dreschler and Zoopage phanera Drechsler. Physico-chemical parameters of waters in basins and water-courses did not prove important effect on existence of fungi. A little more species of predatory fungi were recorded in samples of water in early spring and late autumn.     

Disorders of Blood Pressure Regulation—Role of Catecholamine Biosynthesis,Release, and Metabolism

Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension. This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments.     

Estradiol and regulation of anti-Müllerian hormone, inhibin-A, and inhibin-B secretion: analysis of small antral and preovulatory human follicles' fluid

CONTEXT: In ovaries surgically removed for fertility preservation, hormone concentrations in fluid from small antral follicles were determined. Levels were compared with those found in preovulatory follicular fluid. OBJECTIVE: The objective of this study is to measure intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-A, inhibin-B, estradiol, and progesterone. SETTING: The study was set in a university hospital. PATIENTS: Patients were 22 women suffering from a cancer disease and 16 women undergoing assisted reproduction. INTERVENTIONS: Fluid from 35 follicles (diameter, 3-8 mm) was included and compared with that of 32 preovulatory follicles. MAIN OUTCOME MEASURES: The main outcome measures were intrafollicular concentrations of the measured hormones and their possible correlation. RESULTS: Concentrations of AMH in small antral follicles were almost three orders of magnitude higher than in follicle fluid of preovulatory follicles, 790 +/- 95 vs. 1.17 +/- 0.14 ng/ml (mean +/- sem), respectively. There was a significant negative correlation between estradiol and AMH in fluid from small antral follicles, whereas inhibin-A and inhibin-B were correlated positively with estradiol concentrations. Progesterone showed a similar correlation to levels of AMH but only in fluid of preovulatory follicles. CONCLUSIONS: The high expression of AMH in granulosa cells of small antral follicles actually translates into very high follicle fluid AMH concentrations. This most likely explains the correlation between serum AMH levels and the number of small antral follicles as previously demonstrated. The negative correlation between estradiol and AMH suggests that FSH down-regulates AMH expression. Thus, the microenvironment of the follicle shows profound changes with developmental stage and highlights the importance of studies to understand the mechanisms that regulate follicular growth and development during antral stages of development.     

The Influence of Episode Severity on Caregiver Recall,Care-seeking,and Treatment of Diarrhea among Children 2–59 Months of Age in Bihar,Gujarat, and Uttar Pradesh,India

Increased diarrheal episode severity has been linked to better 2-week recall and improved care-seeking and treatment among caregivers of children under five. Using cross-sectional data from three Indian states, we sought to assess the relationship between episode severity and the recall, care-seeking, and treatment of childhood diarrhea. Recall error was higher for episodes with onset 8–14 days (31.2%) versus 1–7 days (4.8%) before the survey, and logistic regression analysis showed a trend toward increased severity of less recent compared with more recent episodes. This finding indicates that data collection with 2-week recall underestimates diarrhea prevalence while overestimating the proportion of severe episodes. There was a strong correlation between care-seeking and dehydration, fever, vomiting, and increased stool frequency and duration. Treatment with oral rehydration salts was associated with dehydration, vomiting, and higher stool frequency, and trends were established between therapeutic zinc supplementation and increased duration and stool frequency. However, state and care-seeking sector were stronger determinants of treatment than episode severity, illustrating the need to address disparities in treatment quality across regions and delivery channels. Our findings are of importance to researchers and diarrhea management program evaluators aiming to produce accurate estimates of diarrheal outcomes and program impact in low- and middle-income countries.     

What differentiates normal lung repair and fibrosis? Inflammation, resolution of repair, and fibrosis

There has been ongoing controversy related to what differentiates normal lung repair and fibrosis. For example, the current prevailing concept has been that idiopathic forms of pulmonary fibrosis are due only to epithelial injury in response to some unknown cause that results in persistent evolving fibrosis without preceding inflammation. This concept would suggest that the lung responds to injury in a different manner than other organs, such as the liver, kidney, and heart. However, that would seem to contradict known established pathological concepts. To address this controversy, concepts were presented as follows: (1) loss of basement membrane integrity is critical in determining the "point of no return," and contributes to the inability to reestablish normal lung architecture with promotion of fibrosis; (2) loss of epithelial cells, endothelial cells, and basement membrane integrity in usual interstitial pneumonia associated with idiopathic pulmonary fibrosis leads to destroyed lung architecture and perpetual fibrosis; (3) transforming growth factor-beta is necessary, but not entirely sufficient, to promote permanent fibrosis; (4) persistent injury/antigen/irritant is critical for the propagation of fibrosis; (5) idiopathic pulmonary fibrosis is an example of a process related to the persistence of an "antigen(s)," chronic inflammation, and fibrosis; and (6) unique cells are critical cellular players in the regulation of fibrosis. In keeping with the theme of the Aspen Lung Conference, it is hoped that more questions are raised than answered in this presentation, in support of the continued need for research in this area to address these important concepts.     

Distribution,Size, and Origin of Juvenile Chinook Salmon in Shallow-Water Habitats of the Lower Columbia River and Estuary, 2002–2007

Abstract

We monitored fish assemblages monthly at estuarine and tidal freshwater sites in the lower Columbia River and estuary from January 2002 through September 2007 in order to identify specific salmon stocks and migration stages that may benefit from habitat restoration initiatives. We report landscape-scale and seasonal variation in abundance, size, hatchery production (based on adipose fin clips), and genetic stock of origin of juvenile Chinook salmon Oncorhynchus tshawytscha. From fish implanted with coded wire tags (CWTs), we also determined the sites of release and inferred migration patterns. Chinook salmon were found in diverse life history stages and forms, including fry migrants, fingerlings, and (fewer) yearlings. Abundance increased in February and decreased in August, but salmon were present in all months each year. Spatial gradients in abundance and size were strong, with fewer but larger fish in brackish than in tidal freshwater zones. Overall, 30% of the Chinook salmon measured were fry (≤60 mm) that were likely naturally produced fish. These occurred at higher mean monthly proportions in tidal freshwater than in estuarine zones. In contrast, most larger fish were probably raised in hatcheries. Genetic stock assessment revealed that the majority of the Chinook salmon analyzed were from fall-run stock groups originating in the lower Columbia River, with 15% originating from other stock groups. Of these minority contributors, about 6% were identified as upper Columbia River summer–fall-run Chinook salmon while seven other stock groups accounted for the remainder, including 3% from transplants originating in southern Oregon's Rogue River. Recaptures of tagged fish revealed maximum migration times of 143 d for subyearlings and 52 d for yearlings, and both CWT and genetic data indicated that fall Chinook salmon from coastal rivers occasionally entered the estuary. These data demonstrated a widespread temporal and spatial distribution of subyearling Chinook salmon in shallow-water habitats of the lower Columbia River and estuary.

Received June 28, 2011; accepted February 28, 2012