Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Sensitivity and specificity of a self-administered questionnaire for familial screening of adult-onset dystonia.

We developed a self-administered questionnaire for screening the most common adult-onset dystonias. It was tested in 90 first-degree relatives of 22 adult-onset dystonia patients, yielding 79% sensitivity and 94% specificity. Simulation of a case-finding procedure based on serial application of the questionnaire and clinical examination of both subjects screening positive and subjects screening negative who had < 8 years of schooling increased sensitivity to 95% and specificity to 100%. This questionnaire may be an important screening resource for familial aggregation studies to be used in the context of a complex case-finding procedure.     

The multiform and variable patterns of onset of orofacial granulomatosis

BACKGROUND: The recurrent chronic orofacial swelling caused by orofacial granulomatosis (OFG) can cause significant cosmetic and functional problems but can be prevented if the disease is diagnosed early and promptly treated. Although the enlargement of the lips is described to be the most common presenting complaint, the clinical onset of OFG may be characterized by minor associated mucosal and neurological manifestations, making early diagnosis very difficult or, sometimes, merely presumable. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations of 19 patients with OFG, who were examined at our institution between 1998 and 2002, in order to determine their initial manifestations and presenting symptoms. RESULTS: A total of 10 patients showed classical recurrent enlargement of the lips (six lower; four upper) as presenting symptom. In the other nine patients, OFG onset was characterized by transient unilateral facial nerve palsy (two cases), intraoral manifestations (two cases), recurrent swelling of the periorbital area (two cases), of the chin (one case), of the zygomatic area (one case), and of the cheeks (one case). CONCLUSION: Our data underlined that OFG onset could be frequently characterized by widely variable, multiform, and temporary clinical findings. Involvement of atypical sites of the orofacial region and presence of single minor manifestations may occur as presenting symptoms, often preceding the development of traditional clinical findings.     

Bone and joint alterations in acromegaly

Growth hormone (GH) is fundamental for the maintenance of bone mass and metabolism both during childhood and in adulthood. This effect is due to a complex interaction between circulating GH and IGF-I produced peripherally. In vitro data and experimental animal models have clarified many of the regulatory mechanisms underlying the characteristic skeletal changes occurring in acromegaly. This review focuses on the effects of GH excess on bone metabolism and mass in acromegalic patients and, in particular, on the influence of factors such as hypogonadism, gender, age and therapy on bone metabolism and arthropathy.     

Postinfectious gastroparesis related to autonomic failure: a case report

BACKGROUND AND AIM: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing and autopsy. HOSPITAL COURSE: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva manoeuvre although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteraemia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. CONCLUSION: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiological and autonomic studies with histological findings.     

Effects of erythromycin on the propulsive motility of upper gastrointestinal tract in rats

The differences between the postprandial mixing or propulsion and the interdigestive motility of the gastrointestinal (GI) tract are already known. Earlier studies showed dose-dependent differences in the effects of erythromycin on interdigestive motility. The various GI side-effects (vomiting, diarrhoea) also suggest that there are different effects of erythromycin on the GI motility. The aim of our study was to examine postprandially the propulsive effects of different doses of erythromycin on the movement of intraluminal contents in the upper GI tract of the rat. The animals were fasted for 24 h before the experiments but water was given freely. The rats received 1.5 ml 1.5% methylcellulose painted with 0.05% phenol-red intragastrically (test solution). Erythromycin(E. lactobionate) was given intravenously at doses of 0.05, 0.1, 0.25, 0.5, 1.0 and 5.0 mg/kg 15 min before the administration of a test solution. The animals were sacrificed 20,60 and 120 min after administration of methylcellulose, when the distance between the front of the painted intraluminal contents and the pylorus was measured and expressed as a percentage of the total length of small intestine. The phenol-red content in the stomach and small intestine was measured spectrophotometrically and the gastric emptying was calculated from the ratio of the measured total and intestinal phenol-red content. Our results showed that the small doses of erythromycin (0.1 and 0.25 mg/kg) accelerated gastric emptying after 20 min but did not change significantly the propulsive motility of upper small intestine; however, large doses of erythromycin (1.0 and 5.0 mg/kg) decreased gastric emptying and upper GI motility after 20 and 60 min. In summary, the prokinetic action of small doses of erythromycin was demonstrated, but its effecttime on GI motility is short and the ratio of the stimulating and inhibitory doses is 1:10. This paper was presented at the Section of IUPHAR GI Pharmacology Symposium on ’Biochemical pharmacology as an approach to gastrointestinal disorders (basic science to clinical perspectives)‘, October 12-14, 1995, Pécs, Hungary.     

Absence of HIV antigens in renal tissue from patients with HIV-associated nephropathy

HIV-associated nephropathy (HIV-N) is considered a distinctive disease, the pathogenesis of which is still undefined. Direct virus-induced renal cell damage has been postulated. The numerous cytolytic ultrastructural changes and a few studies by immunoperoxidase support this hypothesis, but there has been no demonstration of virus by electron-microscopy (EM) or by tissue culture. In seven out of 12 cases with histological characteristics of HIV nephropathy, with proteinuria (five cases) or with nephrotic syndrome (two cases), we tested renal tissue for HIV antigens: core p18 and p25; envelope gp45 and gp110, by means of immunoperoxidase avidin-biotin complex monoclonal antibodies (MoAbs). Light-microscopy (LM) showed in five patients a focal and segmental glomerular sclerosis, and in two a mesangial hyperplasia with vacuolisation of visceral epithelium and protein inclusions. Electron-microscopy, performed in five of seven patients, showed several protein inclusions in podocyte cytoplasm, tubuloreticular inclusions in endothelial cell cytoplasm in all cases, nuclear degranulation of tubular cells in four cases and nuclear bodies in two. HIV antigens by MoAbs on renal tissue were negative in all cases, in both glomeruli and tubules. These results do not confirm the presence of HIV proteins in renal tissue of patients with HIV nephropathy. A possible explanation, apart from no direct HIV in the disease, may be the low viral load in tissues, because of the early phases of renal damage in most cases.