Thickening Of Capillary Walls Research Articles

Rare coexistence of spinal muscular atrophy with membranous nephropathy - A clinical conundrum with management dilemma.

A 48-year-old male presented with proximal muscle weakness of the shoulder with difficulty in lifting objects above the shoulder in July 2012. Electromyogram was suggestive of chronic motor axonal loss with a myogenic pattern, and a deltoid muscle biopsy revealed groups of atrophic muscle fibers and hypertrophic fibers with pan fascicular atrophy suggestive of adult-onset spinal muscular atrophy. He was managed conservatively and developed bilateral pedal edema in August 2022. He had nephrotic range proteinuria, and renal biopsy revealed capillary wall thickening of glomeruli with serum PLA2R antibody positivity suggestive of primary membranous nephropathy. He was managed with telmisartan for 6 months, and there was a reduction in proteinuria. In January 2023, he was given Injection Rituximab due to worsening proteinuria. He failed to have a clinical resolution. This case report describes the management dilemma in membranous nephropathy with SMA due to the risk of toxic myopathies associated with tacrolimus and steroids.

Acquired diffuse telangiectasias with an unequivocal immunohistochemistry.

A 56-year-old woman presented with abdominal, lumbar and thoracic livedo with 2 years of evolution, consisting of violaceous poikilodermatous patches with scattered petechiae on a base of erythema and telangiectasia, accompanied by diffuse and mild skin atrophy. Histological analysis revealed vasodilation of the superficial dermis and thickening of capillary walls, highlighted by periodic acid–Schiff stain and immunohistochemistry for collagen type IV.

Obesity impacts hypoxia adaptation of the lung.

Obesity is mostly associated with adverse health consequences, but may also elicit favorable effects under chronic conditions. This "obesity paradox" is under debate for pulmonary diseases. As confounding factors complicate conclusions from human studies, this study used a controlled animal model combining diet-induced obesity and chronic hypoxia as a model for pulmonary hypertension and chronic obstructive pulmonary disease. Male C57BL/6 mice were fed control or high-fat diet for 30 wk, and half of the animals were exposed to chronic hypoxia (13% O2) for 3 wk. Hypoxia induced right ventricular hypertrophy, thickening of pulmonary arterial and capillary walls, higher lung volumes, and increased hemoglobin concentrations irrespective of the body weight. In contrast, lung proteomes differed substantially between lean- and obese-hypoxic mice. Many of the observed changes were linked to vascular and extracellular matrix (ECM) proteins. In lean-hypoxic animals, circulating platelets were reduced and abundances of various clotting-related proteins were altered, indicating a hypercoagulable phenotype. Moreover, the septal ECM composition was changed, and airspaces were significantly distended pointing to lung hyperinflation. These differences were mostly absent in the obese-hypoxic group. However, the obesity-hypoxia combination induced the lowest blood CO2 concentrations, indicating hyperventilation for sufficient oxygen supply. Moreover, endothelial surface areas were increased in obese-hypoxic mice. Thus, obesity exerts differential effects on lung adaptation to hypoxia, which paradoxically include not only adverse but also rather protective changes. These differences have a molecular basis in the lung proteome and may influence the pathogenesis of lung diseases. This should be taken into account for future individualized prevention and therapy.NEW & NOTEWORTHY An "obesity paradox" is discussed for pulmonary diseases. By linking lung proteome analyses to pulmonary structure and function, we demonstrate that diet-induced obesity affects lung adaptation to chronic hypoxia in various ways. The observed changes include not only adverse but also protective effects and are associated with altered abundances of vascular and extracellular matrix proteins. These results highlight the existence of relevant differences in individuals with obesity that may influence the pathogenesis of lung diseases.

P17 Photosensitive rashes in the context of alcoholism: a diagnosis to remember

Abstract Pellagra is a disease defined by a deficiency in niacin and its precursor tryptophan. It is a clinical diagnosis characterized by the ‘four Ds’: dermatitis, dementia, diarrhoea and death (Badawy AA. Pellagra and alcoholism: a biochemical perspective. Alcohol 2014; 49:238–50; Pipili C. The diagnostic importance of photosensitivity dermatoses in chronic alcoholism. Dermatol Online J 2008; 14:15). It is predominantly a disease of non-Western countries with low niacin-containing diets, based on maize, with little meat or vegetables. In Western populations, the commonest causes of pellagra include alcoholism, gut malabsorption, some drugs and, rarely, carcinoid, which causes increased conversion of tryptophan to serotonin, depleting niacin precursor stores. The histopathological features of pellagra are nonspecific; however, pallor and keratinocyte ballooning in the upper third of the epidermis can be suggestive. We present two cases of pellagra in the context of alcoholism. Patient 1 was a 58-year-old woman who presented with a 6-week history of a rash on the dorsal hands which spread to the forearms and dorsum of both feet. Examination revealed a photodistributed erythematous rash with a prominent leading edge, wrinkling and hyperkeratosis. She described loss of appetite, diarrhoea and increasing confusion. A punch biopsy from the right forearm showed focal parakeratosis, perivascular inflammation and mild spongiosis with increased mucin in the superficial dermis. A clinical diagnosis of pellagra was suspected, and empirical niacin was prescribed. Patient 2 was a 60-year-old woman who presented with a 1-month history of a progressive itchy rash affecting her arms and legs. Examination revealed a striking photosensitive erythematous rash of her arms and legs, with complete sparing of the inner aspect of the arms. Skin biopsy showed mild keratosis, with subtle thickening of capillary walls. A diagnosis of pellagra was suspected and treatment with oral niacin commenced. Both patients drank alcohol to excess. Both had negative plasma porphyrins and had not started any new drugs and autoimmune screens were normal. The clinical appearance was identical in both cases. Patient 1 continued to drink excess alcohol, but the rash resolved with niacin supplementation. Patient 2 only took a short course of niacin due to significant flushing, but she managed to reduce her alcohol intake significantly and her rash fully resolved. Pellagra is a rare diagnosis in a Western population, but it is an important diagnosis to remember in patients presenting with a photosensitive rash, particularly in the context of alcohol abuse.

Causes and pathological characteristics of native renal thrombotic microangiopathy in an Egyptian population with clinical correlation

Abstract Introduction Thrombotic microangiopathy (TMA) in needle renal biopsy stands as one of the most important diagnostic critical values in nephropathology, and a diagnostic challenge in many of affected patients. The condition has various etiologies with different underlying pathogenetic mechanisms. The urgent handling of such cases with clinical anticipation and histopathological diagnosis draws the management and prognosis of these patients. Objectives In this paper, the histopathological characteristics of native renal TMA lesions were analyzed with determination of the possible underlying etiology and correlation with the clinical findings in Egyptian patients over a duration of 5 years. Patients and methods A retrospective study was conducted to analyze the pathological findings and clinical data of our patients with biopsy-proven renal TMA over a duration of 5 years (from January 2014 to January 2019). One hundred and twenty-seven cases were included. Results The prevalence of native renal TMA in our patients was 3.90% with male: female ratio (0.9: 1) and age range (2–80 years). The most common manifestation was acute kidney injury (64.57%). An underlying etiology was identified in 88 (69.29%) cases and the most common cause was association with autoimmune diseases (27.27%), followed by drug-induced TMA (15.91%), infection-associated TMA, and malignant hypertension (14.77% each). Acute TMA pathological features without evidence of chronicity were seen in 56 (44.09%) cases. The most encountered acute glomerular pathological lesion was irregular capillary wall thickening (68.50%), followed by tuft thrombosis (67.72%) and endothelial swelling (63.78%). Cortical necrosis was detected in 14 (11.02%) patients. The highest percentage of chronic damage features was detected in malignant hypertension and pregnancy-associated TMA. Conclusion TMA is a rare finding in needle native renal biopsy in the study’s Egyptian population with varied underlying etiological agents. The clinicopathological integration and implementing the recent clinical laboratory tests for identification of the underlying etiology of TMA has utmost importance to guide the appropriate management plan of these patients.

Pediatric membranous nephropathy: In the novel antigens era

Membranous nephropathy (MN) falls within the scope of a glomerular disease. MN exhibits subepithelial immune- complex deposition and capillary wall thickening which could occur in all age groups. In comparison with adult patients with MN, MN in pediatric population has a lower incidence and more secondary factors (e.g., systemic lupus erythematosus, infection, malignancy, or drug toxicity). Two target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), found in previous studies and first presented in adult MN, are found in pediatric patients suffering from MN and their antibodies are now an effective tool for diagnosis and monitoring in children and adolescents. Several novel antigens have been identified (e.g., EXT1/EXT2, NELL1, Sema3B, PCDH7, HTRA1, and NCAM1) over the past few years. Each of them represents different clinical and pathologic findings. In-depth research should be conducted to gain insights into the outcomes and pathophysiology of the above novel antigen-associated MN. Targeted treatment opinions for different novel antigen-related MN are under development both in adults and pediatric patients.

Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia, Russia, 2010 to 2019.

Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical and histopathological features of fatal HFRS in the Udmurt Republic (Udmurtia), located in the European part of Russia. This retrospective observational study included all fatal cases of HFRS that occurred in Udmurtia from January 2010 through December 2019. The most relevant clinical and autopsy data of these cases were recorded through a review of the patients’ medical records and autopsy reports. During 2010–2019, Udmurtia had 41 fatal cases of HFRS of a total of 10,312 confirmed cases (case-fatality rate of 0.4%). Twenty-seven patients died in hypotensive and oliguric phases of HFRS due to refractory septic shock and acute respiratory distress syndrome. Fourteen patients died in the polyuric phase of the disease from complications of acute kidney injury or because of hospital-acquired bacterial infections. Multiorgan involvement was noted in all autopsies with variable degrees of generalized venous congestion, interstitial edema, capillary wall thickening, perivascular deposition of plasma proteins, microthrombosis formation, and perivascular hemorrhage. The more prominent histopathological features were seen in kidneys, lungs, and hypophysis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10096-022-04463-y.

Mercury Kushta Induced Histopathological Changes in Kidneys of Wister Rats

Objectives: To see the histological changes of Kushta which contains mercury, on kidneys of wister rats Material and Methods: A total of 42 Wistar rats were used in this animal experiment, which was separated into five exposure groups and one control group. The kidneys of rats were morphologically altered by the use of both indigenous and prescription mercury preparations. Results: Morphological changes in kidneys of exposed rats included multi-focal and diffuse glomerulonephritis, mesangial widening, increase in glomerular cellularity, thickening of capillary walls and glomerular basement membrane, tubular necrosis, tubular dilatation, tubular vacuolisation, proteineous casts in tubules and mononuclear interstitial inflammation were seen at the end of 8 weeks. Conclusions: In wister rats, an indigenous mercury herbo-mineral preparation (Kushta) causes harmful morphological changes in the liver. Keywords: Mercury Kushta, Kidneys, Histopathology

Acoustic Trauma Causes Cochlear Pericyte-to-Myofibroblast–Like Cell Transformation and Vascular Degeneration, and Transplantation of New Pericytes Prevents Vascular Atrophy

Acoustic trauma disrupts cochlear blood flow and damages sensory hair cells. Damage and regression of capillaries after acoustic trauma have long been observed, but the underlying mechanism of pathology has not been understood. We show herein that loud sound causes change of phenotype from neural/glial antigen 2 positive/α-smooth muscle actin negative to neural/glial antigen 2 positive/α-smooth muscle actin positive in some pericytes (PCs) on strial capillaries that is strongly associated with up-regulation of transforming growth factor-β1. The acoustic trauma also reduced capillary density and increased deposition of matrix proteins, particularly in the vicinity of transformed PCs. In a newly established invitro three-dimensional endothelial cell (EC) and PC co-culture model, transformed PCs induced thicker capillary-like branches in ECs and increased collagen IV and laminin expression. Transplantation of exogenous PCs derived from neonatal day 10 mouse cochleae to acoustic traumatized cochleae, however, significantly attenuated the decreased vascular density in the stria. Transplantation of PCs pretransfected with adeno-associated virus 1-vascular endothelial growth factor-A165 under control of a hypoxia-response element markedly promotes vascular volume and blood flow, increased proliferation of PCs and ECs, and attenuated loud sound-caused loss in endocochlear potential and hearing. Our results indicate that loud sound-triggered PC transformation contributes to capillary wall thickening and regression, and young PC transplantation effectively rehabilitates the vascular regression and improves hearing.

Böbrek Hastalıkları ve Lipit Metabolizması

Böbrekler, sıvı-elektrolit dengesinin kontrolü, kandan metabolik atıkları uzaklaştırılması, eritrosit yapımı, kan basıncının düzenlenmesi, kan hacmi ve pH’ının kontrol edilerek asit-baz dengesinin düzenlenmesinde rol oynar. Kronik Böbrek Yetmezliği (KBY) glomerüler filtrasyon değerinde azalmanın sonucu olarak böbreğin sıvı-solüt dengesi ile metabolik-endokrin işlevlerinde kronik ve ilerleyici bozulma olarak tanımlanmaktadır. KBY’de epitelyal hasar, glomerül ve parietal bazal membran hasarı, arteriol ve kapiller damar duvarı kalınlaşması ve lümen daralması, glomerüllerde, tübülüslerde ve membranlarda skleroz, glomerüler filtrasyon hızında (GFH) azalma, nefronların tahribi gibi yapısal değişiklikler görülmektedir. Kronik böbrek yetmezliğinde, böbrek işlevlerinde azalma ile birlikte plazma lipit ve lipoprotein metabolizmasında, lipoproteinlerin hem miktar hem de kompozisyonunda ve apolipoproteinlerde (Apo) önemli değişiklikler oluşmaktadır ve anormal lipit metabolizması böbrek hastalarında yaygındır.

Morphological Changes and Characteristics of the Expression of Serine Racemase in the Rat Hippocampus after Repeated Exposure to Negative Gravitational Overload

Objectives: To study the morphometric parameters and levels of expression of serine racemase in the rat hippocampus after repeated gravitational overloading in the caudocranial direction (–9 Gz). Materials and methods. Rats aged 12 months were subjected to a force of 9 G for 5 min twice a day with 12-h intervals for 28 days (group 2; gravity; n = 10). Rats not exposed to hypergravitation constituted group 1 (controls, n = 10). The morphometric mean areas of the nuclei and perikarya of pyramidal neurons were determined, along with the specific number of neurons with signs of damage and the relative areas of the perikarya of pyramidal neurons and the neuropil. Immunohistochemical studies addressed the level of expression of serine racemase in all zones of the hippocampus. Results. Signs of impaired circulation in the microcirculatory compartment were seen in the form of spongiosis, thickening of capillary walls, and diapedesis of erythrocytes. All zones of the hippocampus in experimental rats showed sharp increases in the numbers of pyramidal neurons with signs of damage. Atrophic changes were identified, consisting of reductions in the mean and relative perikaryon areas of neurons. Immunohistochemical studies demonstrated increased expression of serine racemase in field CA1, along with translocation of reactive material into the processes of pyramidal neurons. Fields CA3 and CA4 showed a tendency to decreases in serine racemase contents. Conclusions. Prolonged gravitation in the caudocranial direction produced signs of marked damage in all hippocampal fields in rats, combined with enhanced expression and accumulation of serine racemase in the dendrites of field CA1 pyramidal neurons, which may be evidence for the involvement of excitotoxicity in the mechanisms of secondary damage in these zones.

Quantitative histomorphometry of capillary microstructure in deep white matter.

White matter lesions represent a major risk factor for dementia in elderly people. Magnetic Resonance Imaging (MRI) studies have demonstrated cerebral blood flow reduction in age-related white matter lesions, indicating that vascular alterations are involved in developing white matter lesions. Hypoperfusion and changes in capillary morphology are generally linked to dementia. However, a quantitative study describing these microvascular alterations in white matter lesions is missing in the literature; most previous microvascular studies being on the cortex. The aim of this work is to identify and quantify capillary microstructural changes involved in the appearance of deep subcortical lesions (DSCL). We characterize the distribution of capillary diameter, thickness, and density in the deep white matter in a population of 75 elderly subjects, stratified into three equal groups according to DSCL: Control (subject without DSCL), Lesion (sample presenting DSCL), and Normal Appearing White Matter (NAWM, the subject presented DSCL but not at the sampled tissue location). Tissue samples were selected from the Cognitive Function and Aging Study (CFAS), a cohort representative of an aging population, from which immunohistochemically-labeled histological images were acquired. To accurately estimate capillary diameters and thicknesses from the 2D histological images, we also introduce a novel semi-automatic method robust to non-perpendicular incidence angle of capillaries into the imaging plane, and to non-circular deformations of capillary cross sections. Subjects with DSCL presented a significant increase in capillary wall thickness, a decrease in the diameter intra-subject variability (but not in the mean), and a decrease in capillary density. No significant difference was observed between controls and NAWM. Both capillary wall thickening and reduction in capillary density contribute to the reduction of cerebral blood flow previously reported for white matter lesions. The obtained distributions provide reliable statistics of capillary microstructure useful to inform the modeling of human cerebral blood flow, for instance to define microcirculation models for their estimation from MRI or to perform realistic cerebral blood flow simulations.

Morphological Changes and Characteristics of the Expression of Serine Racemase in the Hippocampus of Rats Exposed to Multiple Negative Gravitational Overloads

Objectives. To study the morphometric parameters and levels of expression of serine racemase in the hippocampus of rats repeatedly exposed to gravitational overloads in the caudocranial direction (–9 Gz). Materials and methods. Rat aged 12 months were subjected to 9-g forces for 5 min twice a day with 12-h intervals for 28 days (group 2, gravity group, n = 10); controls were not exposed to hypergravitation (group 1, controls, n = 10). Morphometric mean areas of the nuclei and perikarya of pyramidal cells were determined, along with the specific number of neurons with signs of damage, the relative areas of pyramidal neuron and neuroglial cell perikarya. Immunohistochemical studies addressed the level of expression of serine racemase in all zones of the hippocampus. Results. Signs of impaired blood supply in the microcirculatory component were seen in the form of spongiosis, thickening of capillary walls, and diapedesis of erythrocytes. All hippocampal zones in experimental rats showed sharp increases in the numbers of pyramidal neurons with signs of damage. Atrophic changes consisting of decreases in the mean and relative areas of neuron perikarya were identified. Immunohistochemical studies showed increased expression of serine racemase in field CA1, along with translocation of immunoreactive material into the processes of pyramidal neurons. Fields CA3 and CA4 showed a tendency to decreases in serine racemase content. Conclusions. Prolonged gravitational exposure in the caudocranial direction led to the appearance of signs of severe damage in all fields of the rat hippocampus, combined with increased expression and accumulation of serine racemase in the dendrites of pyramidal neurons in field CA1, which may be evidence that excitotoxicity is involved in the mechanisms of secondary damage in this zone.

IgA kappa light and heavy chain deposition disease in multiple myeloma.

A 46-year-old patient was referred to our unit with acute renal failure, his serum creatinine having risen from 137 to 431 μmol/l in eight months. He was born in the Republic of the Congo and had lived in France since 2009. He had no significant previous medical history. On admission, clinical examination was normal except for high blood pressure. Blood analyses confirmed renal impairment. Urine analyses were significant for proteinuria (urinary protein to creatinine ratio 1 g/g), haematuria (105 red cells/ml) and leucocyturia (104 white cells/ml). Serum protein electrophoresis revealed an M-spike and urine protein electrophoresis showed light-chain proteinuria. The paraprotein was identified by immunofixation as immunoglobulin (Ig) A kappa. Bone marrow examination showed 28% clonal plasma cells. Kidney biopsy revealed Congo red-negative thickening of glomerular capillary walls and tubular basement membranes, with peritubular multinucleated giant cells (top left). Electron microscopy showed granular electron-dense material along the lamina rara interna of the glomerular capillary walls and along the outer aspect of the tubular basement membranes (top right). Immunofluorescence confirmed the diagnosis of light and heavy chain deposition disease (LHCDD) by demonstrating staining for IgA heavy chain (bottom left) and kappa light chain (bottom right), without staining for lambda light chain. Haemodialysis was initiated and the patient received first line chemotherapy with bortezomib, cyclophosphamide and dexamethasone. Eight months later, he exhibited an excellent partial haematological response. However, his renal function did not improve and he still required dialysis. Light and heavy chain deposition disease is a very uncommon subtype of monoclonal immunoglobulin deposition disease and only small numbers of cases of IgA kappa LHCDD have been reported. The authors thank the HUPNVS of Assistance Publique - Hôpitaux de Paris for funding publication fees.

Postpartum TTP-HUS Syndrome: A Rare Autopsy Case Report in a Tertiary Care Hospital.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are the two main disorders included under Thrombotic Microangiopathy. 1 in 25,000 pregnancies present with these rare disorders, mostly seen after uncomplicated gestation and delivery . A diagnostic pentad for TTP was given by Amorosi & Ultmann in 1966: thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms and signs, renal functional abnormalities and fever without other explanation. HUS has features of TTP along with acute renal failure.12%-31% of TTP patients are women during pregnancy or postpartum period.Pathological diagnosis requires hyaline thrombi in terminal arterioles andcapillaries. We present a case of a 28 years old primigravida female, with 38 weeks of gestation, who was apparently alright earlier and presented with prolonged second stage of labour. However, day 2 postpartum she developed fever, breathlessness, loose motions and vomiting. She also developed pallor, icterus and petechial haemorrhages.Laboratory investigations revealed low platelet count, elevated bilirubin (direct more than indirect), elevated serum creatinine, and mildly raised hepatic transaminases. Day 5, she developed anuria and grade 3 dyspnoea and succumbed to death. Complete autopsy was performed .Histopathology on sections from kidneys revealed glomerular capillaries and arterioles showing platelet-fibrin thrombi and diffuse thickening of glomerular capillary wall with double contour of glomerular basement membrane. Lungs showed lobar pneumonia. Cause of death given was acute renal failure with lobar pneumonia with HUS-TTP in a postpartum female. TTP-HUS is a rare disorder and although some clinical features may suggest diagnosis, histopathological examination of renal specimen and applying special stains like PAS stain, silver stain and MSB (Mauritus,Scarlet,Blue) stain for fibrin, confirms the diagnosis. DOI: 10.21276/APALM.1240

Physiopathologie, démarche diagnostique et avancées thérapeutiques dans les glomérulonéphrites extra-membraneuses

Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature. The optimal treatment of patients with IMN is still a matter of debate. Thirty to 40% of affected patients will undergo spontaneous remission, usually within one year from disease onset, whereas about one third will progress to end-stage kidney disease. Both the evidence that B cells play a key role in the pathogenesis of IMN and drug toxicity led to target B-cells with rituximab. Rituximab induced remission of nephrotic syndrome in 60 to 80% of the patients with long-lasting proteinuria despite blockade of the renin-angiotensin system and in patients who had previously failed other treatments. Because of the lack of randomized controlled trial (RCT) using rituximab and of high rate of spontaneous remission, a French non-blinded, parallel group RCT was performed to compare rituximab added to supportive therapy, to supportive therapy alone, in patients with persistent nephrotic syndrome.

Glomerulopathy with distinctive fibrillar deposits but lacking glomerular deposition of type III collagen.

A 62-year-old woman with nephrotic syndrome underwent a renal biopsy. Under light microscopy, the biopsy findings included lobulation and enlargement of glomeruli, occasional thickening of glomerular capillary walls, and narrowing of the capillary lumen by swollen endothelial cells. Congo red staining was negative for amyloid. No significant intraglomerular fibrin deposition was found by phosphotungstic acid hematoxylin staining. Immunofluorescence microscopy showed no deposition of immunoglobulin G, A, or M; no κ or λ light chains; and no C3 or C1q. Electron microscopy revealed distinctive subendothelial and mesangial fibrillar deposits, mesangial cell interposition, and swelling and vacuolization of endothelial cells resulting in capillary lumen narrowing. Although some curvilinear fibrillar deposits mimicked the bundles of type III collagen fibers seen in collagenofibrotic glomerulopathy, neither glomerular deposition of type III collagen nor elevation of serum procollagen III peptide was noted. This glomerulopathy does not fulfill any known disease entities with non-amyloid non-immunoglobulin-derived organized glomerular deposits.

Spontaneous early-onset glomerulonephritis in a 8-week-old male Crj:CD1 (ICR) mouse

Glomerular lesions including membranoproliferative glomerulonephritis occur spontaneously in aged mice, but they are rare in young animals. In our laboratory, spontaneous glomerulonephritis was observed in an 8-week-old male Crj:CD1 (ICR) mouse. Macroscopically, the bilateral kidneys were discolored, but no edema or ascites was observed. Glomerular lesions were characterized by a thickening of capillary walls, a double-contoured basement membrane and mesangial expansion due to increased amounts of matrix. Ultrastructurally, mesangial interposition in the capillary wall and subendothelial deposition of basement membrane-like material were observed. No evidence of immune complex deposition or amyloid was found. On the basis of the observed clinical pathology and histopathology, a secondary form of glomerular lesion was excluded. The glomerular lesion was compatible with glomerulonephritis in a young Crj:CD1 (ICR) mouse.

Histopathology of MPGN and C3 glomerulopathies.

'Membranoproliferative' describes glomerular injury characterized by capillary wall thickening and mesangial expansion owing to increased matrix deposition and hypercellularity. The presence of immune deposits is indicative of membranoproliferative glomerulonephritis (MPGN). Historically, MPGN was further classified into three types according to the appearance and site of the electron-dense deposits seen by electron microscopy, but it is now recognized that many cases show only deposition of the complement component C3, owing to abnormal control of the alternative pathway of complement activation-these cases are now classified as C3 glomerulopathies. Not all cases of C3 glomerulopathy, however, show an MPGN pattern. C3 glomerulopathies include dense deposit disease, which shows dense osmiophilic deposits, and C3 glomerulonephritis, which shows isolated deposits. In many cases, the genetic mutations or autoantibodies responsible for C3 deposition have been identified. Some patients in whom complement control is abnormal will accumulate small amounts of immunoglobulin in their glomeruli and so, in everyday practice, the morphological diagnosis of 'glomerulonephritis with dominant C3' is useful for identifying patients who require investigation of the complement pathway. The recognition that many cases of MPGN are C3 glomerulopathies and that the underlying cause can often be identified in immunoglobulin-associated cases means that the diagnosis of idiopathic MPGN is now very uncommon.

Half and half nail.

A 10-year-old boy presented with brown-colored nails since the previous 3 months. He was a diagnosed case of chronic renal failure. The patient denied any history of nail trauma. He also denied history of any drug intake before the development of the lesion. Physical and developmental milestones were normal. Hematological investigations showed raised erythrocyte sedimentation rate with deranged renal function. On nail examination all the 20 nails showed two distinct transverse bands with a brownish red band on the distal part of his nails and proximal white part of the nails having smooth surface and normal nail folds obscuring the lunula [Figure 1]. The demarcation line between the two transverse bands did not disappear on pressure. On the basis of clinical findings, a diagnosis of half and half nails was made. Figure 1 All the 20 nails showed distinct transverse band with the distal brownish red area and proximal white area of the nail plate Half and half nail (brown arcs) is also known as Lindsay's nail, in which proximal portion of the nail is white and the distal half (20-60%) is reddish brown. Although it was first described by Bean[1] in 1963, Lindsay[2] was the first to coin the term half and half nail in 1967. Baran and Gioanni[3] were the first to correlate the half and half nail with renal disease and azotemia in 1968. It usually shows a sharp demarcation line between the two portions, which usually remains parallel to the distal free margin of the nail. There is no correlation between severity of azotemia and the distal band length. It is a rare but special clinical finding seen in chronic renal failure with a prevalence of 15-50%. It can also be seen in yellow nail syndrome, Crohn's disease, Kawasaki's disease, Behcet's disease, cirrhosis, hyperthyroidism, zinc deficiency, citrullinemia, pellagra, HIV infection, and even in healthy persons.[4] The exact pathophysiology of half and half nails is not well understood. The proposed theory is that an increase in capillary density along with capillary wall thickening is responsible for the development of the half and half nail rather than an increase in melanocytes.[5] Treatment is only cosmetic as this is a benign condition that requires only counseling and reassurance. The transition band usually remains unchanged even after dialysis but disappears completely after successful renal transplantation. It usually takes 2-3 weeks for disappearance.[4]