Pathogenesis of migraine

Endothelial cells are not just a semipermeable membrane that forms a barrier between the blood and the vascular smooth muscles. This cell system is a highly active metabolic endocrine organ. It not only produces a number of important substances in vascular and neural homeostasis but also inactivates vasoactive substances such as serotonin and bradykinin. In addition, it produces endothelin-1 and angiotensin II; more importantly in the context of migraine, endothelial cells produce the vasodilators prostacyclin and EDRF-NO, both of which are local (paracrine) hormones. The physiologic function of endothelial cells is affected by aspirin, which prevents prostacyclin formation but has little effect on normal blood pressure. From this information, one can infer that endothelial cell production of prostacyclin does not play an important part in normal cardiovascular control. On the other hand, the administration of Ng-monomethyl-L-arginine causes immediate increases in blood pressure. Because the administration of this substance inhibits the release of EDRF-NO, it appears that this paracrine endothelial hormone actively dilates the normal circulation. It is of cardinal importance that damage or flow perturbations of cell membranes of the endothelial lining of blood vessels cause an increased production of prostaglandins. However, smooth muscle cells underlying the endothelial lining also synthesize prostacyclin. This mechanism is thought to be held in reserve to reinforce local production of prostacyclin and vasodilatation when cell damage to the endothelial lining occurs and EDRF-No is not produced. Many theories for the causation of migraine have been proposed, and some have been reviewed. Those holding sway tend to ignore inconsistencies and cite supporting evidence in favor of their pet explanation only. I therefore have no hesitation to show that the best explanation at present, based on the most recent cellular evidence, explains all features of migraine and the response of migraineurs to therapy. The endothelial cell is the most likely site of the primary abnormality (Fig. 1). Although under physiologic circumstances perivascular innervation and endothelial systems closely interact in the control of vascular tone during pathologic conditions such as ischemia, the dominant role in protecting the circulation is endothelium-mediated. The biology of headache is so diverse and our ignorance sufficiently pervasive that the investigation of endothelial cell function may solve the mystery of migraine. To match the postulated crucial role of the endothelial cell in the pathogenesis of migraine, another cell would have to be ubiquitously present throughout the vasculature and not just confined to the central nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pathogenesis of holoprosencephaly

Holoprosencephaly (HPE), the most common human forebrain malformation, occurs in 1 in 250 fetuses and 1 in 16,000 live births. HPE is etiologically heterogeneous, and its pathology is variable. Several mouse models of HPE have been generated, and some of the molecular causes of different forms of HPE and the mechanisms underlying its variable pathology have been revealed by these models. Herein, we summarize the current knowledge on the genetic alterations that cause HPE and discuss some important questions about this disease that remain to be answered.     

Pathogenesis of asthma

There is now strong evidence that airway inflammation is a predominant underlying problem in patients with asthma, and it has been suggested that ongoing inflammation may lead to airway injury and remodeling. There is also recent evidence that longstanding asthma could be associated with loss of elastic recoil, which can enhance airway obstruction and worsen asthma control [82,83]. Therefore, the use of anti-inflammatory therapy has been advocated in all guidelines, including the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report [84] and its recent update [85] that recommended inhaled steroids as a first mode of therapy for patients with mild, moderate, or severe, persistent asthma. There is preliminary evidence that early institution of anti-inflammatory therapy might lead to disease modification and limit the progression of subepithelial fibrosis and airway remodeling. The pathogenesis of asthma clearly involves many cells and mediators, although the contribution of each individual factor is probably different from patient to patient depending on the setting and stimulus. Although currently available therapies are highly effective in controlling asthma symptoms and limiting exacerbations in the majority of patients, there is still a subset of patients that proceed to develop severe asthma with decreased lung function, lack of responsiveness to therapy, or frequent exacerbations. It is hoped that rapid progress in the area of asthma genetics and pharmacogenetics will yield a more precise and patient-specific understanding of asthma pathogenesis and allow practitioners to prescribe therapies that are designed for a particular patient or exacerbation. That will undoubtedly help to improve the care of asthma, limit its morbidity, and reduce the side effect of medications.     

曲霉的致病机制

曲霉是一种自然界中广泛分布的真核生物,免疫抑制状态的患者吸入其孢子可导致严重的肺部感染[1].曲霉感染率随免疫抑制人群的增长而迅速上升[2].曲霉感染后症状无特异性,易被忽视,病死率高[3].曲霉病临床表现多样,其中甚为重要的类型是侵袭性曲霉病,侵袭性曲霉感染是指曲霉侵入人体组织、血液,并在其中生长繁殖引致组织损害、器官功能障碍和炎症反应的病理改变及病理生理过程,特征即为曲霉菌丝侵袭血管[4-5]. 即使及时、合理的使用抗真菌药物,侵袭性曲霉病全身播散治疗的有效率仍仅为9%～18%[6].体外实验表明灭活的曲霉菌丝仍能侵入血管内皮细胞,造成损害[5].这从另一方面表明仅仅使用抗真菌药物来改善曲霉感染预后的效果可能很有限,因而必须在曲霉致病机制上有所突破.     

Pathogenesis of asthma

The conception of the pathogenesis of a disease is probably as important in determining the selection of therapies as is the evidence provided by outcome studies of their efficacy. The recent evolution in our understanding of the pathogenesis of asthma has nicely paralleled advances in clinical research on new forms of treatment. This evolution has occurred so smoothly that we may not be fully aware how far it has taken us. Airflow obstruction is still regarded as the fundamental cause of the characteristic asthmatic symptoms of shortness of breath, chest tightness, and wheezing, while the factors leading to airflow obstruction are still assumed to include spasm of airway smooth muscle, thickening of the airway wall, and inspissation of viscid plugs of mucus in the airway lumen. What is new is the recognition of asthma as a chronic disease of the lower airways associated with characteristic inflammatory changes (involving lymphocytes, mast cells, and eosinophils), and possibly irreversible "remodeling" of the airways (by deposition of collagen and proteoglycans, proliferation and transformation of resident cells, and infiltration with inflammatory cells). This modern conception of asthma differs dramatically from the former perception of the disease as an episodic illness characterized by disturbance of the contractile function of airway smooth muscle. The new interpretation has important implications not just for the development of future therapies based on the inflammatory mechanisms involved in the pathogenesis of asthma, but also for the ways in which current therapies should be used.     

Pathogenesis of COPD

Chronic obstructive pulmonary disease (COPD) is not a single disorder. Rather, it is a collection of disorders characterized by the progressive development of airflow limitation. Patients afflicted with COPD experience systemic effects that are often responsible for major clinical problems. Lesions with differing pathogenetic bases can contribute to airflow limitation, and these differing and overlapping pathogenetic mechanisms account for the heterogeneous clinical features of COPD.     

Pathogenesis of edematous states

Edema is a clinical sign reflecting an increased volume of sodium and water in the interstitial space. Two types of abnormal renal sodium handling have been described in edema forming states. In the first, a primary disturbance in renal function leads to sodium retention, plasma volume expansion and, ultimately, edema formation. This type of edema is called primary edema, an "over-flow" or "nephritic" edema. By contrast, in the other type of edema, renal sodium retention seems to be attributable to a decreased effective arterial blood volume. This is "underfill" or "nephrotic" edema.     

Pathogenesis of gastrointestinal infection

The last 30 years has seen the recognition of many intestinal pathogens, through a combination of microscopy, tissue availability and open minds. In the developing world the challenge to eradicate such infections continues, especially in infancy and early childhood. In developed communities, however, the challenge is shifting to pathogens ('super bugs') arising from our own interventions and lifestyles which will occupy many future careers.