A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clinical and histomorphometric characteristics of three different families with hereditary gingival fibromatosis

Objective. To examine the histomorphologic and histomorphometric features of tissue from 3 unrelated families with hereditary gingival fibromatosis (HGF).Study design. Twelve affected individuals from 3 HGF families and 3 control subjects were evaluated. Gingival samples were fixed in formalin and embedded in paraffin for hematoxylin and eosin stain to count the number of fibroblast and inflammatory cells. Sirius red staining was performed to quantitate the amount of collagen present.Results. Histomorphologic analysis of HGF showed extension of epithelial rete ridges into the underlying lamina propria and the presence of collagen bundles in the connective tissue. Analysis of the mean area fraction of collagen showed that there were significant increases in the collagen fraction for all HGF types compared with control subjects (P < .05). There were significant increases in the number of fibroblasts for HGFa and HGFb compared with control subjects (P < .05). The number of fibroblasts for HGFc were similar to that for control subjects.Conclusions. The collagen fraction was significantly greater in all HGF types compared with controls. The number of fibroblasts was significantly increased in 2 of the 3 HGF types compared with controls. These data indicate that different mechanisms may be responsible for tissue enlargement in different forms of HGF.

Effect of cyclosporine on adriamycin induced nephritis

The effects of cyclosporine A (CSA) administration, started as early as renal lesion is induced, on the development of Adriamycin-induced nephropathy were assessed by comparing the time course of this nephropathy in rats receiving CSA with that in non-treated animals (group ADR) over 16 weeks. Throughout the experiment, no significant difference in proteinuria was observed between the groups. At the end of the experiment, there was no significant difference between the groups regarding the frequency of glomerular lesion (Group AADR: Md=23%, P25=15%, P75=75%; Group ADR-CSA: Md=48%, P25=11%, P75=70%); tubulointerstitial lesion index (Group ADR: Md=1.5, P25=1.0, P75=2.5); glomerulosclerosis area (Group ADR = 18.2 +/- 4.2%; Group ADR-CSA = 13.2 +/- 1.4%); and, interstitial fibrosis area (Group ADR+V: 1.75 +/- 0.10%; group ADR-CSA: 1.34 +/- 0.09%). In conclusion, CSA, when, administered since nephropathy induction does not change the course of the disease.

Paulista registry of glomerulonephritis: 5-year data report

Background. The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of São Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care.Methods. This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire.Results. The mean age of the patients was 34.5 +/- 14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%).Conclusion. Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.

THE LONG-TERM EVOLUTION OF IMMUNE DEPOSITS IN PASSIVE HEYMANN NEPHRITIS

1. To study the long term course of passive Heymann nephritis (PHN), 42 adult male Wistar rats were injected with rabbit anti-FX1A serum (PHN group) and 42 rats received normal rabbit serum (control group). Two animals from each group were sacrificed 2 weeks after the inoculation and 10 animals each from the control and PHN groups were sacrificed 4, 13, 25 and 53 weeks later.2. The PHN group exhibited a significant elevation in 20-h proteinuria which lasted from the first week (control group, 9.19 +/- 0.87; PHN group, 25.3 +/- 2.66) to the 25th week (control group, 22.6 +/- 2.15; PHN group, 66.7 +/- 10.4) except for week 17. From week 29 to week 53 there was no statistical difference between the 2 groups.3. Light microscopy showed no difference between the kidneys of PHN and control rats. Immunofluorescence microscopy in PHN rats showed granular deposition of autologous and heterologous IgG on the glomerular basement membrane (GBM), whose intensity and pattern did not change during 53 weeks of observation.4. When examined by electron microscopy the glomeruli of PHN rats showed: a) electron-dense deposits which were initially subepithelial and homogeneous and later intramembranous, granular and often surrounded by an electron-transparent halo; b) focal thickening of the GBM at the sites of intramembranous deposits; c) effacement of podocytes located close to the deposits; d) penetration of the podocytes into the GBM associated with the deposits; e) presence of osmiophilic granules in the cytoplasm of the podocyte located inside the GBM similar to the granules of the deposits next to them. The association of the penetration of the podocytes into the GBM with the deposits and the presence of the osmiophilic granules inside the foot process have not been described previously in PHN.5. The results suggest that the podocytes play a role in the clearing of intramembranous deposits in PHN.

Hereditary equine regional dermal asthenia in three related Quarter horses in Brazil

Hereditary equine regional dermal asthenia belongs to a group of inherited, congenital connective tissue dysplasias usually described as hyperelastosis cutis, cutaneous asthenia, dermatosparaxis, or Ehlers-Danlos-like syndrome. This report presents the clinical and histological features of three related Quarter horses affected with regional dermal asthenia. These horses had bilateral asymmetric lesions of the trunk and lumbar regions, where the skin was hyperextensible. Handling of the skin elicited a painful response and superficial trauma led to skin wounds. The skin was thinner than normal in the affected areas, with thickened borders and harder fibrotic masses (pseudotumours). The histopathological findings included thinner and smaller collagen fibrils, and a loose arrangement of collagen fibres in the middle, adventitial and deep dermis. Masson's trichrome and Calleja stains did not reveal any abnormality of collagen and elastic fibres. Electron microscopy showed no abnormalities. As in human patients, pseudotumour histopathological findings included fibroplasia and neovascularization. The pedigree chart of these animals supports an autosomal recessive type of inheritance, which has been suggested by other studies. This is the first report of this disease in Brazil. Its clinical and histological features resemble those described in horses affected with this condition in the United States.

Rat nephrotoxic nephritis. The relation between the type and intensity of induced histological lesions and the content of antiglomerular basement membrane antibodies of the inoculated serum

Six groups of 6 rats received equal doses (0.8 ml/100 g of body weight) of different rabbit anti rat kidney sera. The titer of anti GBM antibodies in the sera was evaluated by indirect immunofluorescent test in isolated GBM (IIT GBM). Rats of groups 1, 2, 3, 5, 6 received anti rat GBM sera with titers of 1/320, 1/240, 1/160, 1/60, 1/30 respectively. Group 4 received anti rat kidney serum with a titer of 1/80. The rats of group 1 died from 1 to 5 minutes after inoculation and their kidney were congested, with hialine trombi occluding arterioles and glomerular capillaries. The rats of group 2 and one of group 3 died from 2 to 15 days after inoculation and diffuse cortical necrosis was found. The remaining rats were sacrificed 2 months after inoculation. The kidneys were normal in control group; chronic membranoproliferative glomerulonephritis was observed in group 3 and 4, membranoproliferative glomerulonephritis in group 5 and minimal changes in group 6. By immunofluorescence rabbit gammaglobulin was seen in GBM of group 3, 4, 5 and 6. The IIT GBM performed in the eluates of the kidneys revealed the presence of heterologous antibody in groups 1, 2, 3, 4, 5 and 6 and autologous antibody in groups 3, 4 and 5. One concludes that the IIT GBM identifies and quantifies antibodies which have the property of damaging the kidney.

Treatment of rat nephrotoxic nephritis. Use of 5-fluorouracil or methotrexate-5-fluorouracil association

To evaluate the effect of 5-fluorouracil (F) and methotrexate-5-fluorouracil association (MTX-F) on nephrotoxic nephritis, seven groups of 10 rats were inoculated with anti-rat glomerular basement membrane serum (AGBMS); five groups were treated with different doses of F, beginning on the 2nd or the 6th day, one group with MTX-F beginning on the 2nd day and one group (control) with distilled water. Twenty-four hour proteinuria was determined weekly until the 71st day. The kidneys were examined histologically and by immunofluorescence. The group treated with F (1.3 mg/100 g body weight) developed a severe glomerulonephritis similar to the control group; (b) the groups treated with F (2.0 mg/100 g body weight) or with MTX-F showed progressively lower proteinuria, less severe histological changes and less intense fluorescence due to autologous antibodies. The best results were observed in the MTX-F group and in the F group treated from the 6th day. These groups presented at the 71st day proteinuria of 84 and 91 mg as compared to 312 mg in the control group, and minimal histological lesions as compared to glomerulosclerosis and tubular atrophy in the control group. We concluded that either F or MTX-F produced significant improvement of nephrotoxic nephritis due to inhibition of autologous antibody production.

Renal interstitial foam cells are macrophages

Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells.

Oral manifestations of Albright hereditary osteodystrophy: a case report.

Albright hereditary osteodystrophy is a hereditary metabolic disorder of dominant autosomal etiology that is commonly characterized by short stature, round face, small metacarpus and metatarsus, mental retardation, osteoporosis, subcutaneous calcification, variable hypocalcemia, and hyperphosphatemia. In this study, we report a clinical case of a 17-year-old woman with Albright hereditary osteodystrophy, and we discuss her clinical, radiographic, and laboratory test characteristics together with the oral manifestations, and we correlate them with the characteristics found in the literature. We also discuss the odontological management of treatment of related periodontal disease and planning for corrections of related malocclusions.

Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet

Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule. © 2006 International Society of Nephrology.