Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H(2)S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H(2)S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet.</p><p><b>METHODS</b>C57BL/6 mice and homozygous apoE(-/-) mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE(-/-) mice were treated with the same dose of normal saline as the apoE(-/-) group, injected intraperitoneally with sodium hydrosulfide (NaHS, an H(2)S donor, 56 µmol/kg per day) as the apoE(-/-) + NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-γ-lyase inhibitor, 50 mg/kg, per day) as the apoE(-/-) + PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit.</p><p><b>RESULTS</b>Compared with control mice, apoE(-/-) mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE(-/-) mice, H(2)S donor-treated apoE(-/-) mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H(2)S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE(-/-) mice, PPG treated apoE(-/-) mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE(-/-) + PPG rats did not significantly differ from those in the apoE-/-mice. Consistently, H(2)S induced SOD expression, accompanied by a reduced level of ROS.</p><p><b>CONCLUSION</b>H(2)S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE(-/-) mice fed with a Western type diet.</p>

Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The number of Clara cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.</p><p><b>METHODS</b>Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS + NAC group) oral intake of NAC 80 mg x kg(-1) x d(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The mRNA expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.</p><p><b>RESULTS</b>Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3 +/- 14.7 vs. 53.7 +/- 11.5, P < 0.05). The Clara cell particles in cytoplasm decreased in the CS group (P < 0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8 +/- 4.3 and 29.5 +/- 2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1 +/- 3.8 and 43.8 +/- 5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P < 0.05). No significant difference was observed in GSH level ((181 +/- 26) nmol/L in the control group vs. (170 +/- 18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1 +/- 17.5) decreased (P < 0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213 +/- 40) nmol/L vs. (170 +/- 18) nmol/L in the CS group) increased too (P < 0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1 +/- 6.4 and 34.3 +/- 6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P > 0.05). No significant difference was found in the expression of CC16 mRNA among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r = -0.592, P < 0.05), but not with GSH level.</p><p><b>CONCLUSIONS</b>One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.</p>

Effect of sulfur dioxide on pulmonary vascular structure of hypoxic pulmonary hypertensive rats / 中华儿科杂志

<p><b>OBJECTIVE</b>Hypoxic pulmonary hypertension is an important pathophysiologic process of various cardiovascular diseases. Sulfur dioxide (SO2) was considered as a kind of toxic gas previously, but recent studies suggested that SO2 could act as a key bioactive molecule in the pathogenesis of cardiovascular diseases. Therefore, this study was designed to examine the effect of sulfur dioxide on pulmonary vascular structure of hypoxic pulmonary hypertensive rats treated with SO2 donor substances.</p><p><b>METHODS</b>The rats were randomly divided into 3 groups: control group(n = 8), hypoxic group(n = 8) and hypoxic + SO2 group (n = 10, treated with SO2 donor Na2SO3/NaHSO3). The rats of hypoxic group and hypoxic + SO2 group were under a hypoxic condition for 21 days, while the rats of control group were exposed to room air. The mean pulmonary artery pressure was tested by means of right cardiac catheterization and the content of SO2 in plasma was investigated by high performance liquid chromatography (HPLC). The change in relative medial thickness (RMT) of pulmonary arteries was examined under optical microscope. The ultra-structural changes were observed under a transmission electron microscope. The data were analyzed through one-way analysis of variance (ANOVA) by SPSS 13.0 software.</p><p><b>RESULTS</b>Compared with control group [(2.25 +/- 0.50) kPa], the mean pulmonary artery pressure of hypoxic group [(5.12 +/- 0.51) kPa] raised significantly (t = 5.091, P < 0.01) and RMT of hypoxic group (9.66 +/- 1.27) compared with control group (6.83 +/- 1.57) significantly raised (t = 3.392, P < 0.01). Ultrastructural observation showed the proliferation and degeneration of endothelial cells in small pulmonary arteries in rats with pulmonary hypertension. The internal elastic lamina was irregular. The proliferation of medial smooth muscle cells of arteries was shown at the level of respiratory bronchioles. The collagens also increased. Meanwhile, compared with control group [(33.36 +/- 5.62) micromol/L], the content of SO2 in plasma of hypoxic group [(27.01 +/- 4.17) micromol/L] declined (t = 2.067, P < 0.05). Whereas compared with that of hypoxic group [(5.12 +/- 0.51) kPa], the mean pulmonary artery pressure of hypoxic + SO2 group [(3.94 +/- 0.33) kPa] declined (t = 2.712, P < 0.01) and RMT of hypoxic + SO2 group (6.97 +/- 1.83) decreased compared with hypoxic group (9.66 +/- 1.27) (t = 3.009, P < 0.01). Compared with those of hypoxic group, the pulmonary artery ultrastructural changes in hypoxic group ameliorated obviously after using exogenous sulfur dioxide donor. The endothelial cells became flat and the smooth muscle cells of arteries slightly enlarged and arranged regularly. At the same time, compared with hypoxic group [(27.01 +/- 4.17) micromol/L], the content of SO2 in plasma of hypoxic + SO2 group [(29.89 +/- 4.52) micromol/L] raised (t = 1.263, P > 0.05).</p><p><b>CONCLUSION</b>Sulfur dioxide plays an important role in the regulation of small pulmonary artery structural changes in hypoxic pulmonary hypertensive rats. The hypoxic pulmonary hypertensive damages can be ameliorated significantly after using exogenous SO2 donor.</p>

Correlation of brain hypoxia at different degrees with brain function and brain damage investigated using near infrared spectroscopy / 中华儿科杂志

<p><b>OBJECTIVE</b>To study correlation of brain hypoxia of different degrees with brain function and damage.</p><p><b>METHODS</b>The brain regional oxygen saturation (rSO2) was determined by using a non-invasive near infrared spectroscopy (NIRS) technique in 15 piglets; the piglets were subjected to inhale 3% - 11% oxygen-nitrogen mixed gas through mechanical ventilation for 30 min. The piglets were divided into groups according to the level of brain rSO2 (i.e. < 30%, 30% - 35%, 35% - 40%, and 40% - 50%), and the data were compared with those of the control group (rSO2 > 60%). Changes of brain function were detected through amplitude and frequency of EEG waves and signal complexity. The piglets were sacrificed via decapitation 72 h after brain damage, and then histopathological and ultrastructural examinations were performed on cerebral cortex and hippocampal CA1 area.</p><p><b>RESULTS</b>In the group with rSO2 > 40%, the mean arterial pressure (MAP) after hypoxia was (56 +/- 0.00) mm Hg (1 mm Hg = 0.133 kPa), the blood lactic acid (LA) was (2.3 +/- 1.2) mmol/L, the EEG findings were within normal range, and there was no change in brain tissue ultrastructure. In the group with brain rSO2 = 30% approximately 40%, the MAP was (73 +/- 8) mm Hg, the LA was (8.2 +/- 3.9) mmol/L, the EEG waves showed decreased amplitude, frequency and complexity, but restored to some extent after hypoxia. The brain tissue ultrastructure showed damages to the cerebral cortex and neuron mitochondria at hippocampal CA1 area. In the group with brain rSO2 < 30%, the MAP was (35 +/- 0) mm Hg, the LA was (12 +/- 2) mmol/L, the EEG showed decreased amplitude, frequency, and complexity of signals compared with those of the normal control group, and was difficult to restore after hypoxia in some of the piglets; the brain tissue ultrastructure appeared to be similar to the changes seen with high-degree swollen cerebral cortex and neuron mitochondria at hippocampal CA1 area.</p><p><b>CONCLUSION</b>Different degrees of hypoxia had different influence on brain function and brain damage. The lower the brain rSO2, the more severe the damages to the brain and its function. The rSO2 of brain tissues detected with noninvasive NIRS can reflect brain injury and its severity during cerebral anoxia.</p>

The pathological characters and its clinical significance of internal hemorrhoids / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the pathological characters and the corresponding clinical significance of internal hemorrhoids tissues.</p><p><b>METHODS</b>Normal anal cushion and internal haemorrhoids tissue samples were obtained after stapled haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The macroscopically normal cushions served as own controls and the normal cushions from a patient without a history of haemorrhoids as quality control. Routine Hematoxylin-Eosin and orcein were performed for elastic fibers.</p><p><b>RESULTS</b>Compared with the corresponding normal anal cushions, the subepithelial vessels especially the cavernous vessels of the hemorrhoidal tissues showed obvious structural impair, retrograde changes, and the internal elastic lamina were ruptured and discontinuous. In addition, thrombosis and subsequent ischemic changes were observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy, distortion, rupture and tortility. Obvious mucosal injury was observed in the mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the hemorrhoidal tissues.</p><p><b>CONCLUSIONS</b>The anal cushions of hemorrhoids disease patients show significant pathological changes. The pathological changes include structural impair, retrograde changes of the cavernous vessels and the hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the fibroelastic tissues, and mucosal injury of the mucous membranes. These pathological changes are the basis of pathogenesis and development of hemorrhoids.</p>

Treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury.</p><p><b>METHODS</b>The model of rat acute rectal mucous injury was established by 3% acetic acid. Two hundred and forty rats were divided equally into control and experimental group. The rats of experimental group were administrated with 20 mg carraghenates suppository via rectum twice a day, but rats of control group were not administrated with carraghenates suppository. Thirty rats in both groups were executed at different time points. The pathologic changes were observed and the rectal mucous injury was scored. Immunohistochemical staining was used to evaluate the effect of carraghenates suppository on expression of VEGF, iNOS, IL-8, MMP9, HIF-1 alpha and PCNA in the two groups.</p><p><b>RESULTS</b>The scores of rectal mucous injury was lower, the pathologic changes such as hyperaemia, edema, destroy of glands were less severe, and tissue repair time was shorter in experimental group compared with those in the control group at 24 h, 78 h and 120 h after administration of carraghenates suppository. No obvious cicatrisation was observed in experimental group. Expression of VEGF and MMP9 was significantly lower in experimental group compared with those in the control group at 24 h after administration. Expression of VEGF, iNOS, IL-8, MMP9, HIF-1alpha and PCNA were statistically decreased in experimental group than those in the control group at 72 h, 120 h after administration. MVD in experimental group was statistically decreased than that in the control group.</p><p><b>CONCLUSION</b>The compound carraghenates suppository can reduce the rectal mucous injury from 3% acetic acid, and accelerate the wound healing without obvious cicatrisation. The compound carraghenates suppository can reduce the expression of MMP9, VEGF, IL-8, PCNA, iNOS and HIF-1 alpha, which may play a role in its protective mechanism.</p>

Changes of pulmonary artery structural remodeling in pulmonary hypertension induced by high pulmonary flow in rats / 中国医学科学院学报

<p><b>UNLABELLED</b>To explore the changes of time-dependent pulmonary artery structural remodeling in pulmonary hypertension induced by high pulmonary flow in rats.</p><p><b>METHODS</b>Eighty male SD rats were randomly divided into control group (n =40) and shunt group (n = 40). Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the control group, rats experienced the same experimental processes except the shunting procedure. After 1 day, 3 days, 1 week, 4 weeks, and 8 weeks of experiment, systolic pulmonary artery pressure (SPAP) and mean pulmonary artery pressure (MPAP) of each rat were evaluated by using a right cardiac catheterization procedure. Heart tissues were separated as right ventricle (RV) and left ventricle plus septum (LV+SP), and the ratio of RV to LV+SP [RV/ (LV+ SP)] was calculated. The morphologic changes including micro- and ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. The percentages of muscularized artery (MA), partial muscularized artery (PMA) and non-muscularized artery (NMA) in small pulmonary arteries and median pulmonary arteries were calculated. The changes of relative medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were examined.</p><p><b>RESULTS</b>Compared with control group, SPAP and MPAP did not change on day 1, day 3, and week 4. However, in week 1 and week 8 of experiment, SPAP and MPAP increased significantly (P < 0.01). Meanwhile, in week 8 of experiment, RV/ (LV+SP) increased significantly (P < 0.05). In contrast to control group, the percentages of MA, PMA, and NMA did not change in day 1, day 3 and week 1. But in week 4 and week 8, the percentages of MA and PMA increased significantly (P < 0.01) but that of NMA decreased significantly (P < 0.01). RMT and RMA did not change in day 1, day 3, week 1 and even week 4 in shunt group as compared with those of control group, but they increased significantly in week 8 (P < 0.05). The changes of ultra-structure of pulmonary arteries included that endothelial cells became swollen and large in size on day 3, smooth muscular cells increased in size besides the change of endothelial cells in week 1, and they changed from contractile phenotype to synthetic phenotype in week 4. Collagen deposited in pulmonary arteries markedly in week 8.</p><p><b>CONCLUSION</b>Pulmonary artery structural remodeling develops in a time-dependent manner. Endothelial cells of pulmonary arteries become swollen firstly, followed by the proliferation of smooth muscular cells and finally by remodeling of extra cellular matrix.</p>

Pathologic change of elastic fibers with difference of microvessel density and expression of angiogenesis-related proteins in internal hemorrhoid tissues / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the pathological variations in internal hemorrhoid and evaluate the expression of nitric- oxide synthase(NOS),vascular endothelial growth factor(VEGF),matrix metalloproteinase- 2(MMP2) and MMP9.</p><p><b>METHODS</b>Normal anal cushion and internal hemorrhoids tissue samples were obtained from 24 patients with iii degree hemorrhoids after procedure for prolapse and hemorrhoids(PPH) procedure. The expression of NOS, VEGF, MMP2, MMP9 and CD34 were detected by immunohistochemical staining; the microvessel density (MVD) was counted by anti- CD34 antibody; the elastic fibers were detected by orcein staining.</p><p><b>RESULTS</b>There were statistically significant differences in the expression of MVD, VEGF, MMP9 between internal hemorrhoid tissue and normal anal cushions(P< 0.05). iNOS was significantly increased in hemorrhoid tissue, but no significant difference between normal anal cushions and hemorrhoid tissue. Morphological abnormalities such as breaking, distortion, mortality, hyaline degeneration were found in elastic fibers of internal hemorrhoid tissue, but not in normal anal cushions.</p><p><b>CONCLUSION</b>Angiogenesis is evident in hemorrhoid tissue, suggesting the possible mechanism in the pathogenesis of hemorrhoids. The direct degeneration effect of MMP9 on supporting structure elastic fibers in anal cushion is another important mechanism. The high expression of iNOS suggests the inflammatory factors involve in the pathogenesis of hemorrhoids, and NO may be involve in pathological effect on hemorrhoids.</p>

Observation of Dynamic Changes in Ultra-Micro-Structure of Pulmonary Arteries and Endogenous Hydrogen Sulfide in Rats with Left-Right Shunt / 实用儿科临床杂志

Objective To explore the relationship between dynamic changes in ultra-micro-structural of pulmonary arteries and endogenous hydrogen sulfide in rats with left-right shunt.Methods Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of pulmonary artery structural remodeling. After 1 day, 3 days, 1 week, 4 weeks and 8 weeks of experiment, the ultra-micro-morphologic changes of pulmonary arteries of rats were observed under electronic microscope and H_2S concentration in serum was evaluated by modified sulfide electrode method.Results The changes of ultra-micro-structure of pulmonary arteries were progressively exacerbated, endothelial cells became swollen and large in size on 3 days, smooth muscular cells increased in size as well as the change of endothelial cells in 1 week, and they changed from contractile phenotype to synthetic phenotype in 4 weeks.Conclusions Shunt exhibited changes of ultra-micro-structure of pulmonary arteries are accompanied by the changes of endogenous H_2S. It is suggested that endogenous H_2S might play a protective role in changes of ultra-micro-structure of pulmonary artery.

Effect of naloxone on neuronal cells apoptosis induced by repeated febrile seizures / 实用儿科临床杂志

Objective To investigate the effect of naloxone on neuronal cells apoptosis induced by repeated febrile seizures(FS).Methods Warm water was used to induce 70 rats FS model 15 days after birth in this study; each rat was induced 7 times febrile seizures at one- day interval . Seventy rats were randomly divided into naloxone-treated group and FS control group, receiving injection of naloxone or saline at 5, 30, 60 min and 2 hours after FS each day respectively. The rats were sacrificed 24 hours after the last seizure. Neuronal cell apoptosis was determined by TUNEL methods in situ cell death kit. TUNEL positive cells(TPC) were stained and counted as apoptosis in hippocampus and cortex. Ultrastructural changes of apoptosis neurons were observed under the electron microscope(EM). Results Compared with the FS control group, naloxone treatment could significantly relieve neuron apoptosis induced by repeated FS when it was used at 5, 30, 60 min after the last FS. However there was no significant difference in neuron apoptosis between 2 groups when naloxone was used at 2 hours after FS. The comparison of different naloxone administration time showed that the earlier naloxone was injected,the fewer apoptosis neurons were induced by FS.Conclusion Naloxone,as early used in proper dosage,may significantly alleviate apoptosis after repeated FS ,and protect neurons.

Endogenous nitric oxide pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling / 中华儿科杂志

<p><b>OBJECTIVE</b>Pulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left-to-right shunt. However, the mechanism is still not clear. The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow.</p><p><b>METHODS</b>Sixteen male SD rats were randomly divided into control group (n = 8) and shunting group (n = 8). Aortocaval shunting was produced for 11 weeks in shunt rats. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] was detected. Pulmonary vascular micro-and ultra-structure was examined by using a light microscope and a transmitted electronic microscope. Meanwhile, the concentration of plasma NO was measured by spectrophotometry. The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively.</p><p><b>RESULTS</b>After 11-week aortocaval shunting, mPAP was significantly increased [(22.5 +/- 2.6) mmHg vs. (15.8 +/- 2.8) mmHg, 1 mmHg = 0.133 kPa, t = 4.97, P < 0.01], and RV/(LV + S) was also markedly increased (0.267 +/- 0.022 vs. 0.221 +/- 0.016, t = 4.85, P < 0.01). The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23.2 +/- 2.4)% vs. (13.5 +/- 2.1)%, t = 7.82, P < 0.01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery: (7.76 +/- 0.56)% vs. (4.82 +/- 1.03)%, t = 6.23, P < 0.01; small pulmonary artery: (11.94 +/- 0.66)% vs. (6.91 +/- 0.53)%, t = 14.96, P < 0.01]. Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased [(30.2 +/- 7.9) micromol/L vs (19.7 +/- 5.7) micromol/L, t = 3.05, P < 0.01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group.</p><p><b>CONCLUSION</b>The upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling.</p>

The clinicopathological features of early renal amyloidosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological manifestations of early renal amyloidosis (AL) and its diagnostic criteria.</p><p><b>METHODS</b>Fifteen cases with early renal amyloidosis admitted from 1994 to 2001 were collected from the hospital, and their clinical and pathological features were reviewed. Of them, the initial diagnoses were not made by depending findings from the light microscopy (LM) and immunofluorescense (IF), but confirmed by electron microscopy (EM) afterwards. Immuno-electron microscopy (IEM) were applied for amyloidosis typing.</p><p><b>RESULTS</b>Most patients of early renal AL were in the middle to old age. Nephrotic syndrome was the most prominent symptoms and signs accompanying with rare microscopic hematuria and hypertension. Most of them had a normal renal function. Pathological examinations of renal biopsies using LM and IF showed mild mesangial proliferation and mild thickening of glomerular basement membrane (GBM). Immunoglobulins and complements were negative or only scanty in certain cases, but in all cases there was a light chain protein deposition homogeously. There were 4 cases of minimal change glomerulopathy, 5 cases of mild mesangial proliferative glomerulonephritis, 5 cases of stage I membranous nephropathy, and 1 case of cast nephropathy diagnosed with LM. The amyloid fibrils (diameter 8 - 10 nm) were randomly distributed in the mesangium, along GBM and at the arteriolar wall under EM. Additionally, Congo red staining was positive. IEM demonstrated that amyloid fibrils labeled with colloid gold was combined with a kind of light chain protein which was confirmed as the light chain type of AL.</p><p><b>CONCLUSIONS</b>The diagnosis of early renal AL was occasionally neglected by depending only findings of LM and LF. However, special amyloid fibrils can be detected using EM. EM observation is an indispensable technique for the diagnosis of early renal AL and the typing of AL may further be determined by using IEM.</p>

Pathological features of light chain nephropathy / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the pathologic features and diagnostic algorithm of light chain nephropathy (LCN).</p><p><b>METHODS</b>Seven cases of LCN were studied by light microscopy, electron microscopy and immunolabeling of light chains (kappa, lambda) by immunofluorescence and immunoelectron microscopy.</p><p><b>RESULTS</b>The histopathology of 7 cases by light microscopy was variable, with 3 cases showing nodular glomerulosclerosis, 1 case showing mild to moderate mesangial proliferation, and 3 cases showing cast nephropathy with minimal glomerular change. Immunofluorescence study revealed positive staining of a single type of light chain in mesangium (nodular pattern) or along glomerular basement membrane (linear), along tubular basement membrane and around arteriolar walls in all the 7 cases. Ultrastructurally, electron-dense granular deposits were identified in mesangium, subendothelial aspect of glomerular basement membrane, outer aspect of tubular basement membrane and arteriolar walls. Immunogold labeling of light chains showed distinct labeling of a single type light chain in the granular electron-dense materials (5 cases being kappa-positive and 2 being lambda-positive).</p><p><b>CONCLUSIONS</b>LCN typically shows nodular glomerulosclerosis. The ultrastructural change is characteristic and important for diagnosis. Immunolabeling of light chains by immunofluorescence and immunoelectron microscopy carries further diagnostic value, especially in cases with minimal light microscopic change.</p>