Generalized Vascular Dissection on Pathological Examination in a Patient With Polycystic Kidney Disease and Acute Aortic Dissection

Polycystic kidney disease (PKD) is a multiple cystic disease involving both the kidneys. Some studies have reported cases of patients with PKD and concurrent aortic dissection; however, autopsy has been performed in only few of these cases. Here, we present the case of a 62-year-old male patient with PKD who showed generalized vascular degeneration, including aortic dissection. The patient had a family history of autosomal dominant PKD and was brought to our hospital because of cardiopulmonary arrest. He was diagnosed with Stanford type A aortic dissection and died on the same day, despite being under cardiopulmonary resuscitation. Autopsy detected multiple cysts in the kidneys, liver, pancreas, and testes. Moreover, multiple tears in the vascular wall of the splenic artery and superior mesenteric artery, including the aorta, were observed. The case findings indicate that patients with PKD may develop associated generalized vascular disease; however, development of cerebral aneurysms and aortic dissections with PKD is particularly serious. Therefore, suitable screening tests must be developed for the early diagnosis and disease characterization, thus, ensuring that the appropriate treatment is administered to the patients.     

High-Fat Diet–Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice Are Reduced by Inhibiting Sialidases

High-fat diet (HFD)–induced inflammation and steatosis of adipose tissue and liver are associated with a variety of serious health risks. Sialic acids are found as the distal terminal sugar on glycoproteins, which are removed by sialidases (neuraminidases). In humans and mice, pulmonary fibrosis is associated with up-regulation of sialidases, and injections of sialidase inhibitors attenuate bleomycin-induced pulmonary fibrosis. Sialidase levels are altered in obese rodents and humans. This report shows that for mice on an HFD, injections of the sialidase inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid inhibit weight gain, reduce steatosis, and decrease adipose tissue and liver inflammation. Compared with control, mice lacking the sialidase neuraminidase 3 have reduced HFD-induced adipose tissue and liver inflammation. These data suggest that sialidases promote adipose and liver inflammation in response to a high-fat diet.

In the United States, approximately 40% of adults are obese (body mass index, ≥30 kg/m²), leading to an estimated annual medical cost of $150 billion and approximately 200,000 deaths.1, 2, 3 Obesity is one of the most prominent risk factors for many chronic diseases, including type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Approximately 25% of adults in highly industrialized nations have nonalcoholic fatty liver disease, with approximately 5% of them having nonalcoholic fatty liver disease with liver inflammation (hepatitis), a more serious condition called nonalcoholic steatohepatitis.4, 5, 6 Up to 40% of individuals with nonalcoholic steatohepatitis progress to advanced liver fibrosis and eventually cirrhosis.⁷Obesity is the accumulation of body fat as the result of excessive food intake and/or lack of exercise. Obesity induces adipocyte metabolic dysregulation and the production of inflammatory cytokines, leading to systemic metabolic dysregulation, such as the inability to effectively control systemic glucose levels (insulin resistance), elevated lipid levels (dyslipidemia), and immune cell recruitment to, and activation in, adipose tissue and liver (inflammation).⁸ Excess calories lead to elevated circulating levels of glucose and free fatty acids, which force adipocytes to accumulate more lipid and expand in size, leading to increased oxidative stress in adipocytes and local hypoxia of the tissue, due to the inability of oxygen to diffuse across the tissue.^8,9 These processes lead to adipocyte cell death, initiating the activation of adipose tissue macrophages.^9,10 In the liver, excess calories lead to Kupffer cell (hepatic macrophage) activation, which promotes inflammation and increased hepatocyte fatty acid synthesis, leading to hepatic steatosis (abnormal retention of lipids within the hepatocytes) and eventual fibrosis or cirrhosis.^8,11Sialic acids are often found as the distal terminal sugar on the oligosaccharide chains of glycoconjugates, such as glycoproteins. Sialidases (alias neuraminidases) are enzymes that remove this sialic acid from glycoconjugates.¹² Neuraminidase (NEU) 1 to 4 are the four sialidases seen in mammals.¹³ N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) inhibits mammalian sialidases.¹⁴ Previous studies have found that injections of DANA or lack of NEU3 both attenuate bleomycin-induced lung fibrosis in mice.^15,16 The role of sialidases in the regulation of high-fat diet–induced obesity is unclear, with up-regulation or down-regulation of different sialidase proteins in different tissues, suggesting a complex association between obesity and sialidases.17, 18, 19 Changes in sialidase levels appear to lead to the dysregulation of insulin signaling and glucose metabolism.^18,19Because excess calories lead to adipose tissue and liver inflammation, steatosis, and fibrosis, and because injections of DANA and lack of endogenous NEU3 both inhibit bleomycin-induced lung inflammation and fibrosis, this study examined whether injections of DANA and/or endogenous NEU3 could inhibit obesity-induced adipose tissue, liver inflammation, and steatosis in a mouse model.     

Factors predisposing to exercise-induced late asthmatic responses

Seventeen children developed reproducible early and late asthmatic responses (dual reactions) after cycle ergometer exercise. There was a significant correlation between the magnitude of their early and late reactions, emphasizing the direct relationship of these events. No significant differences were observed in the clinical severity of asthma, diurnal variations in FEV1, and extent of the early reaction after exercise between children with dual responses and 19 children with single reactions. These findings suggest that the occurrence of late reactions after exercise is not determined by differences in severity of disease or baseline airway reactivity in the asthmatic subjects. This view is supported by the finding that there was no significant difference in the dose of acetylcholine necessary to elicit a 20% decrease in FEV1 between eight children with dual response and seven children with single early response after exercise. The rate of spontaneous recovery from early reactions was slower in children with dual responses, suggesting that this variable may predict development of late-phase reactions in exercise-induced asthma.     

Eustachian tube function: physiology,pathophysiology, and role of allergy in pathogenesis of otitis media

Otitis media may be the result of Eustachian tube dysfunction or inflammation of the middle ear, or both. The Eustachian tube may be either abnormally patent (patulous or semipatulous) or, more commonly, obstructed. Functional obstruction is most likely due to either lack of tubal stiffness or an abnormal active opening mechanism, e.g., inefficient tensor veli palatini muscle. Mechanical obstruction may be secondary to extrinsic causes such as a nasopharyngeal tumor or possibly an adenoid mass. Intrinsic obstruction can result from an upper respiratory tract infection. Even though proof that allergy is causally related to otitis media is lacking, recent studies indicate that the Eustachian tube can become partially obstructed when upper respiratory allergy is present. In addition, there is now some evidence that in a small percentage of children with upper respiratory allergy, the middle ear may be a “shock organ.” Future studies are needed to define the role of allergy in the pathophysiology of the Eustachian tube and the pathogenesis of otitis media. Randomized clinical trials will be required to determine the efficacy of the currently popular forms of immunotherapy and allergy control in the prevention of otitis media.