Arterial renin--partial characterization and its possible role in the pathogenesis of hypertension

1) Renin-like enzyme of rat aorta was purified by chromatography with DEAE-cellulose and Sephadex G-200. 2) The molecular weight of renin-like enzyme was 124,000 and 72,000 on Sephadex G-200 gel filtration. The isozymes, however, migrated as a single band with molecular weight of 71,000 on SDS/polyacrylamide gel electrophoresis. These isozymes showed the same optimal pH (6.5) and temperature (37 degrees C). 3) Renin-like enzyme showed high activity in the microsomal fraction of the aorta. 4) In one-clip, two-kidney Goldblatt hypertensive rats, the aortic renin concentration increased significantly, but not parallel with the activity in plasma. 5) Renin, widely distributed in subcellular fractions of the aorta, may play a possible role in the local control of vascular tone. It is likely that renin in vascular wall is of local origin.     

Short report: possible Cryptosporidium muris infection in humans

Oocysts of cryptosporidia whose morphology resembled that of Cryptosporidium muris were found in the stool of 2 healthy girls in Surabaya, Indonesia. The oocysts were predominantly oval and measured 7.75+/-0.17 x 5.55+/-0.13 microm (mean+/-SD). The number of oocysts excreted were more than 10(5) per gram of stool. The oocysts were well stained with fluorescein-conjugated monoclonal antibody to Cryptosporidium. The specimens from both girls containing the oocysts showed a positive result by the polymerase chain reaction (PCR) using primers specific for the genus Cryptosporidium, but a negative result by the PCR using primers specific for C. parvum. The 2 girls passed oocysts for 5 and 6 days, respectively. They did not complain of any symptoms during the passage of oocysts.     

Short report: detection of Orientia tsutsugamushi in clinical samples by quantitative real-time polymerase chain reaction

Orientia tsutsugamushi infection causes scrub typhus, a common zoonosis of rural Asia. Orientia tsutsugamushi was recently detected by a real-time quantitative polymerase chain reaction (qPCR) assay in animal specimens. We evaluated the same qPCR assay in specimens obtained from patients with serologically proven scrub typhus infections. The 47-kDa qPCR assay was more sensitive than was mouse inoculation; it was reactive in whole blood specimens from all 10 isolate-positive patients and in 7 of 17 isolate-negative individuals (P = 0.003, Fisher's two-tailed exact test). As few as 1,076 O. tsutsugamushi copies/microL were detected in whole blood. Four of 7 sera from isolate-proven scrub typhus infections were also reactive by qPCR. The assay was unreactive in all 12 individuals without scrub typhus infection. This is the first demonstration of a sensitive and specific real-time qPCR assay for human scrub typhus infection.     

Gastroesophageal reflux and its possible role in the pathogenesis of upper aerodigestive tract disorders

Associations have been reported between gastroesophageal reflux (GER) and a variety of upper and lower respiratory tract conditions. Respiratory conditions and GER are common and would be expected to coexist in many patients. Whether there is a relationship between GER and these conditions, its nature still remain controversial, the data available are frequently conflicting and furthermore the direct association between symptoms and reflux is often difficult to establish. For this reason, the majority of clinicians still treat extraesophageal manifestations of GER empirically as esophageal pH testing is not routinely used in the ear, nose and throat (ENT) practice. Purpose of this paper is to examine the relationship between GER and these conditions both in adults and children, through a PubMed database systematic review.     

环状RNA在心血管疾病中的发病机制及临床应用

环状RNA(circRNA)在细胞中广泛存在且稳定表达,可作为重要的调控元件充当微小RNA和RNA结合蛋白的海绵,参与调控转录、翻译、剪切等过程,影响心脏炎性反应信号通路、血管平滑肌细胞功能、心肌细胞肥厚与凋亡、脂质代谢等过程.该文介绍了circRNA心血管疾病早期诊断、治疗靶点、风险分层的基本特点.     

Adherence of mycoplasmas: Phenomena and possible role in the pathogenesis of disease

Mycoplasma pneumoniae attaches to a variety of surfaces. Adherence to inert surfaces such as glass requires an intact energy metabolism. Interaction with sheep erythrocytes occurs via a binding protein on the mycoplasma surface. The protein reacts with a receptor containing sialic acid. Adherence to other erythrocytes may involve different mechanisms. Different results have been reported on interaction with tissue cells. The various mechanisms probably cooperate and thereby facilitate the colonization of the human respiratory tract.     

Placental ferritin in coeliac disease: relation to clinical stage, origin, and possible role in the pathogenesis of malignancy.

Placental ferritin is a tumour associated antigen present in the serum of patients with active Hodgkin's and non-Hodgkin's lymphoma, and the serum values fall during remission of the disease. There is no correlation between placental and total blood ferritin values. Because of the strong association between coeliac disease and lymphoma, 19 children with active and 25 with inactive coeliac disease were screened for the presence of placental ferritin. Thirty two children with other intestinal disorders served as controls. Placental ferritin was identified by using a monoclonal antibody in an ELISA procedure. The mean (SEM) placental ferritin value in the control serum was 12.6 (2.4) while the values in serum of patients with active and inactive coeliac disease were 117 (22.8) and 43.8 (10.2) U/ml respectively. Patients with active coeliac disease differed significantly from both control subjects (p = 0.0004) and those with inactive disease (p = 0.03). Peripheral blood lymphocytes contained no placental ferritin. It was present, however, in lamina propria lymphocytes of intestinal biopsy specimens from active coeliacs. Placental ferritin was also found in some of the better differentiated malignant cells in two patients with adult onset enteropathy associated lymphoma. Placental ferritin is known to have an immunosuppressive effect, and this may be one of the necessary steps in the development of malignancy associated with coeliac disease. Gluten free diet, by reversing this state, may have a role in the prevention of lymphoma.     

Atrial natriuretic factor--its possible role in the pathogenesis and therapy of arterial hypertension

Using radioimmunoassay the authors investigated the plasma concentration of the immunoreactive atrial natriuretic factor (IR-ANF) and its content in the atria of 4-, 8-, 12-, 16-, and 20-weeks-old spontaneously hypertensive rats (SHR), and compared the results with data obtained in normotensive Wistar-Kyoto rats of the same age. With hypertension accelerating in SHR between the 8th and the 20th weeks of life, IR-ANF content in the atrium gradually decreased, and the plasma IR-ANF concentration increased. The decline in IR-ANF was due to its decrease primarily in the left atrium. Long-term (6-day) administration of synthetic ANF to SHR with fully developed hypertension led to normalization of BP. The results do not support the hypothesis that arterial hypertension in SHR is induced by a primary deficiency of ANF. The changes in IR-ANF in the atria and plasma occur rather as an adaptive and regulatory response to increasing BP. Prolonged administration of ANF to SHR had a hypotensive effect. Therapeutic application of ANF in man depends on the development of oral and long-acting analogues.     

Functional dyspepsia： The role of visceral hypersensitivity in its pathogenesis

Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.     

Wegener's granulomatosis: Possible role of environmental agents in its pathogenesis

OBJECTIVE: To investigate the possibility that environmental agents contribute to the pathogenesis of Wegener's granulomatosis (WG). METHODS: We undertook an extensive search for possible environmental exposures by developing a comprehensive questionnaire that was administered by telephone interview to 53 patients with WG and 2 control groups: one with osteoarthritis and the other with gout. Questions focused on hobbies and vocations, work, home, and allergies. Exact logistic regression was used to calculate odds ratios and 95% confidence intervals after adjusting for potential confounders. After adjusting for age and sex, data are reported for all exposures with odds ratios >2.0 against either control group or for any allergic propensity. RESULTS: Results suggest that mercury and perhaps lead exposure were positively associated with WG as compared with either control group, although the number of patients exposed was small. A prior history of allergy was also associated with WG as compared with either control group. CONCLUSION: We conclude that heavy metal exposure and a prior history of allergy may play a role in the etiopathogenesis of Wegener's granulomatosis.     

The possible role of postprandial hyperglycaemia in the pathogenesis of diabetic complications

It is both common and wise practice to adjust the treatment of diabetic patients to obtain plasma glucose concentrations as close as possible to the "normal range", correcting both postprandial hyperglycaemic spikes and the less increased, but persistently high, plasma glucose concentration between meals. The Diabetes Control and Complications Trials (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have provided evidence that intensive treatment can prevent complications associated with diabetes mellitus. In both studies, effectiveness of hyperglycaemic treatment was assessed by means of the glycated haemoglobin level. This is an integrated measure of both postprandial and fasting hyperglycaemia. The absolute and relative importance of the two conditions, however, could differ depending upon the organ or system suffering from diabetic complications and other more or less known individual factors. This paper aims to emphasize the effects of acute hyperglycaemia, in particular, postprandial hyperglycaemia, on the development of diabetic complications. The role of oxidative stress as a mediator of acute hyperglycaemia is further discussed. More investigation in this area is required so that treatment can be eventually individualised. Perhaps, in some patients, efforts could be concentrated on the control of hyperglycaemic spikes and/or specific organ or system susceptibility to either acute or chronic hyperglycaemia.     

The possible role of hepatitis A virus in the pathogenesis of atherosclerosis

The possible association between hepatitis A virus (HAV) infection and coronary artery disease (CAD) was studied. Blood from 391 patients undergoing coronary angiography was tested for serum IgG antibodies to HAV and C-reactive protein (CRP). Of the 391 patients, 205 (52%) had anti-HAV IgG antibodies. CAD prevalence was 74% in HAV-seropositive and 52% in HAV-seronegative patients (P<.0001); significance persisted after adjustment for either traditional CAD risk factors or for risk factors plus other infectious agents (cytomegalovirus, Chlamydia pneumoniae, Helicobacter pylori, and herpes simplex virus). In addition, CRP levels were significantly higher in HAV-seropositive than in HAV-seronegative patients (P=. 013) in both univariate and multivariate analyses. Logistic regression analysis demonstrated that HAV seropositivity is an independent predictor of risk for CAD and elevated CRP levels. HAV infection is therefore associated with CAD, which raises the possibility that this virus may play a causal role in atherogenesis.     

Ghrelin in neonatal rats: distribution in stomach and its possible role

Ghrelin, a 28 amino acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. The fact that administration of ghrelin, centrally or peripherally, stimulates both food intake and GH secretion suggests that stomach ghrelin has an important role in the growth of rats. We used immunohistochemistry and radioimmunoassay to determine the age at which ghrelin-immunostained cells begin to appear in the rat stomach. Ghrelin-immunoreactive cells were found to be expressed in the fetal stomach from pregnancy day 18. The number of ghrelin-immunoreactive cells in the fetal stomach increased as the stomach grew. The amount of ghrelin in the glandular part of the rat stomach also increased, in an age-dependent manner, from the neonatal stage to adult. Eight hours of milk restriction significantly decreased the ghrelin concentration in the stomachs of 1-week-old rats, and increased the ghrelin concentration in their plasma. Administration of ghrelin to 1- and 3-week-old rats increased plasma GH concentrations. The daily subcutaneous administration of ghrelin to pregnant rats from day 15 to day 21 of pregnancy caused an increase in body weight of newborn rats. In addition, daily subcutaneous administration of ghrelin to neonatal rats from birth advanced the day of vaginal opening from day 30.7+/-0.94 to day 27.9+/-0.05. These results suggest that ghrelin may be involved in neonatal development.     

Lymphocyte homing and its role in the pathogenesis of IBD

Inflammatory bowel disease (IBD) is an idiopathic disorder of chronic inflammation of the gastrointestinal tract. Experimental models of IBD and results from human genomewide linkage studies suggest that the primary defect that leads to IBD is an inappropriate mucosal immune response to normal intestinal microbes. Genetic alterations not only confer increased susceptibility to IBD but also appear to determine the nature and location of the intestinal inflammation, as is evident in patients with genetic alterations of NOD2 and their susceptibility for ileal Crohn's disease. IBD has traditionally been classified into 2 subtypes, namely, ulcerative colitis (UC) and Crohn's disease (CD), based on histological appearance and anatomical distribution. However, an increasing body of data supports the concept that IBD is an umbrella diagnosis encompassing a variety of disorders with distinct genetic, microbial, and environmental determinants that cluster either into a UC or CD phenotype. The shared common pathway is uncontrolled intestinal inflammation. A key element in the pathogenesis of intestinal inflammation in both UC and CD is increased leukocyte recruitment from the circulation, and this provides a potential target for pharmaceutical inhibition. In this article we review the current understanding of the molecules that determine leukocyte trafficking to the gut and highlight opportunities where their inhibition could be exploited to treat IBD.(Inflamm Bowel Dis 2008).