Amadori albumin in type 1 diabetic patients: correlation with markers of endothelial function, association with diabetic nephropathy, and localization in retinal capillaries

Nonenzymatic glycation is increased in diabetes. Most studies so far have focused on the role of advanced glycation end products (AGEs) in vascular complications, whereas the role of early glycation Amadori-modified proteins, which is the predominant form of glycated proteins, has not been systemically investigated in humans. We developed an antiserum against glycated human serum albumin (HSA) and used this to study the role of early glycation products in vascular complications in type 1 diabetic patients. Amadori albumin was determined to be the recognition epitope of the antiserum. The antibody recognized a specific glucose adduct and a conformational component specific for human albumin in Amadori albumin, with no recognition of AGEs. Plasma Amadori albumin levels were significantly higher in type 1 diabetic patients (n = 55) than in healthy control subjects (n = 60) (39.2+/-9.9 vs. 20.9+/-4.0 U/ml, P < 0.0005). Amadori albumin correlated with levels of plasma markers of endothelial function von Willebrand factor (r = 0.29, P < 0.05) and vascular cell adhesion molecule-1 (r = 0.41, P < 0.005), but not soluble E-selectin. In addition, Amadori albumin immunoreactivity was detected in the capillaries of retinas of diabetic patients. Plasma levels of Amadori albumin were determined in a second group of type 1 diabetic patients with long-standing diabetes with (n = 199) or without (n = 192) diabetic nephropathy. Patients with nephropathy had higher Amadori albumin levels than did those without it (50.9+/-9.5 vs. 45.1+/-6.3 U/ml, P < 0.0005). Age-, sex-, and diabetes duration-adjusted analyses showed that nephropathy was significantly associated with Amadori albumin with an odds ratio (OR [95% CI]) of 1.11 [1.08-1.15] per U/ml increase. After additional adjustment for levels of creatinine, glycated hemoglobin, cholesterol, triglycerides, blood pressure, preexistent retinopathy, and cardiovascular disease, Amadori albumin continued to be significantly associated with nephropathy (OR 1.06 [1.01-1.11]) per U/ml increase. Our results are consistent with a proposed pathophysiological role of Amadori albumin in microvascular complications of type 1 diabetic patients.     

Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus.

It is a widely held view that when a patient with type I diabetes mellitus and diabetic retinopathy or neuropathy develops renal impairment the renal lesion will be diabetic glomerulonephropathy. This has been extrapolated to apply to type II diabetes. We have performed a retrospective study of the clinical data of patients with diabetes mellitus who have had a renal biopsy between November 1980 and December 1990. Seventy-one patients were biopsied, data were available on 68. Nineteen of 22 type I diabetics had diabetic glomerulopathy, two had diabetic glomerulopathy in addition to another lesion only one patient did not have diabetic glomerulopathy. Twenty-three of 46 type II diabetics had diabetic glomerulopathy alone 22 having an alternative diagnosis. Eight further patients were identified who were not known to be diabetic at the time of renal biopsy, but whose biopsies revealed diabetic glomerulopathy. These data suggest that patients with type II diabetes and renal impairment should have a renal biopsy as part of their investigation.     

Increased prevalence of scoliosis in Turner syndrome.

Turner syndrome (TS) is associated with multiple skeletal abnormalities. However, the prevalence of scoliosis in children with TS has not been reported in the orthopaedic literature. The purpose of this study was to determine the prevalence and characteristics of scoliosis in these patients. The authors performed a retrospective study of 43 patients with TS and found 5 children with a curve >10 degrees. The prevalence of scoliosis in this TS population, 11.6%, was significantly greater than the reported prevalence of idiopathic scoliosis in normal girls, 2.4%. The mean age of onset was 9 years 11 months. All curves were >34 degrees, with curves consisting of a right thoracic or S-shaped (larger lumbar segment) pattern. At the time of scoliosis presentation, two patients were not receiving growth hormone therapy. The results of this study suggest that children with TS need to be examined and closely monitored for progression of scoliosis by orthopaedists. Although curve progression can occur during growth acceleration, a direct causal association with growth hormone has not been established.     

Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: implications in retinal neovascularization

OBJECTIVEArachidonic acid is metabolized by 12-lipoxygenase (12-LOX) to 12-hydroxyeicosatetraenoic acid (12-HETE) and has an important role in the regulation of angiogenesis and endothelial cell proliferation and migration. The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV).RESULTSRetinal NV during OIR was associated with increased 12-LOX expression and 12-, 15-, and 5-HETE production. The amounts of HETEs also were significantly higher in the vitreous of diabetic patients with PDR. Retinal NV was markedly abrogated in mice treated with baicalein or mice lacking 12-LOX. This was associated with decreased VEGF expression and restoration of PEDF levels. PEDF expression was reduced in 12-HETE–treated rMCs, astrocytes, and the retinal pigment epithelium. Only rMCs and astrocytes showed increased VEGF expression by 12-HETE.CONCLUSIONS12-LOX and its product HETE are important regulators of retinal NV through modulation of VEGF and PEDF expression and could provide a new therapeutic target to prevent and treat ischemic retinopathy.Retinal neovascularization (NV) is a vision-threatening complication of ischemic retinopathy that develops in various retinal disorders, including diabetic retinopathy and retinopathy of prematurity (ROP). Retinal NV is controlled by a balanced production of pro- and antiangiogenic factors, including vascular endothelial growth factor (VEGF) and pigment epithelium–derived factor (PEDF), respectively (1). However, under some pathological conditions, including diabetic retinopathy and ROP, this balance is disrupted by enhanced production of proangiogenic and/or downregulation of antiangiogenic factors (2,3).Arachidonic acid metabolites, which are known as eicosanoids, are involved in regulating angiogenesis (4). Once released by cytosolic phospholipase A₂ (5), arachidonic acid is metabolized via different pathways, including the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 pathways. Angiogenesis has been shown to be promoted by the metabolic products of COX2, prostaglandins (6) and the products of the lipoxygenase system, leukotrienes, and hydroxyeicosatetraenoic acids (HETEs) (7,8). LOXs are a group of closely related dioxygenases that catalyze the stereospecific oxygenation of arachidonic acid and other polyunsaturated fatty acids (PUFAs) and are classified as 5-, 8-, 12-, or 15-LOX, according to the site of oxygen insertion within arachidonic acid.Three types of 12-LOX have been characterized: platelet, leukocyte, and epidermal 12-LOX (9), which are detected in various cell types, including smooth muscle cells (SMCs) (10), endothelial cells (10,11), and glial cells (12). The major product of 12-LOX metabolism of arachidonic acid, 12-HETE has a role in various biological processes, including atherogenesis, cancer cell growth, and neuronal apoptosis (13,14). In addition, 12-HETE has proinflammatory effects (15,16) and has been implicated in diabetic vascular complications (13). For example, high glucose treatment increases 12-HETE production in vascular endothelial cells and SMCs, and this increase is linked to vascular endothelial growth factor (VEGF) upregulation (17,18) and leukostasis (19) in the intracellular adhesion molecule-1–dependent pathway (15). Similarly, 12-HETE has been shown to contribute to tumor angiogenesis via a VEGF-dependent pathway (20) and to stimulate endothelial cell mitogenesis (7,8) and tube formation (21).VEGF and PEDF are identified as key angiogenic factors whose altered production contributes to the development of retinal NV. They induce opposite effects in the retina, which causes vasculopathies associated with diabetic retinopathy and ROP. Although VEGF has angiogenic and permeability effects that were shown to be mediated via oxidative stress (22,23) and inflammatory pathways (24), PEDF elicits antiangiogenic and antipermeability effects in part through antioxidant (25,26) and anti-inflammatory mechanisms (27). There are multiple cellular sources for the growth factors involved in retinal NV. Müller cells (rMCs) are known to express several modulators of angiogenesis by responding to hypoxia or hyperglycemia and releasing VEGF (28,29). They also are shown to have an antiangiogenic background attributed to PEDF secretion (30). Moreover, VEGF and PEDF expression in rMCs are altered by a high glucose concentration, which contributes to retinal NV in diabetic retinopathy (31).The role of lipoxygenases in general, and 12-LOX in particular, in the development of retinal NV has not been well investigated. The goal of this study was to explore the changes in 12-LOX expression and activity during retinal NV and to determine whether targeting 12-LOX activity impacts retinal NV perhaps through changes in the level of angiogenic factors.The current study presents, for the first time, that oxygen-induced ischemic retinopathy (OIR) and proliferative diabetic retinopathy (PDR) are associated with increased 12-LOX expression and activity. Inhibition of the LOX pathway or 12-LOX deletion significantly abrogated retinal NV and VEGF expression, while preserving retinal PEDF levels during OIR.     

Increased presence of capillaries next to remodeling sites in adult human cancellous bone

Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remodeling sites, capillaries, proliferative cells, and putative osteoblast progenitors. Iliac crest biopsies from normal human individuals were subjected to histomorphometry and immunohistochemistry to identify the respective positions of bone remodeling sites, CD34‐positive capillaries, smooth muscle actin (SMA)‐positive putative osteoblast progenitors, including pericytes, Ki67‐positive proliferative cells, and bone remodeling compartment (BRC) canopies. The BRC canopy is a recently described structure separating remodeling sites from the bone marrow, consisting of CD56‐positive osteoblasts at an early differentiation stage. We found that bone remodeling sites were associated with a significantly increased presence of capillaries, putative osteoblast progenitors, and proliferative cells in a region within 50 µm of the bone or the canopy surface. The increases were the highest above eroded surfaces and at the level of the light‐microscopically assessed contact of these three entities with the bone or canopy surfaces. Between 51 and 100 µm, their densities leveled to that found above quiescent surfaces. Electron microscopy asserted the close proximity between BRC canopies and capillaries lined by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic‐vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis, and points to the BRC canopy as a central player in this mechanism. We propose a model where initiation of bone remodeling coincides with the induction of proximity of the vasculature to endosteal surfaces, thereby allowing capillary‐BRC canopy interactions that activate marrow events, including recruitment of osteoblast progenitors to bone remodeling sites. © 2013 American Society for Bone and Mineral Research.     

Increased hemoglobin AIc in diabetic mice.

The minor hemoglobins AIa, AIb, and AIc were studied in mice with either genetic or chemically induced diabetes. Hemoglobin AIc was elevated approximately twofold in all the phenotypically diabetic mice studied (C57BL/KsJ-db/db, C57BL/KsJ-ob/ob, C57BL/6J-db/db, and alloxan- and streptozotocin-treated mice). Elevation of the hemoglobin AIc in C57BL/6J-db/db mice was of short duration, reflecting the transitory diabetes characteristic of these mice. The degree of increase of hemoglobin AIc levels was unrelated to severity of hyperglycemia, duration of diabetes, age of mouse, or body weight. It is not known what factor(s) dictates the steady-state concentration of hemoglobin AIc.     

Increased expression of heparanase in overt diabetic nephropathy

In overt diabetic nephropathy (DNP), an increase in the permeability of the glomerular basement membrane (GBM) has been associated with a loss of negatively charged heparan sulfates (HS) in the GBM. Heparanase (HPSE), an endo-beta(1-4)-D-glucuronidase, can cleave HS and could be a potential candidate for the degradation of glomerular HS, leading to the development of proteinuria. We analyzed whether changes in HS expression are associated with HPSE expression in overt DNP. Immunofluorescence staining was performed to analyze HS, HPSE, and agrin core protein expression in kidney biopsies from patients with overt DNP and from rats and mice with streptozotocin (STZ)-induced diabetes. We also investigated the effect of transgenic HPSE overexpression in mice on glomerular HS and agrin expression. We demonstrate that the loss of GBM HS (-50%) and tubular HS (-60%) is associated with a four-fold increased HPSE expression in overt DNP. In addition, glomerular HPSE expression is upregulated in rats (messenger RNA (mRNA) 2.5-fold, protein three-fold) and mice (mRNA seven-fold, protein 1.5-fold) with STZ-induced diabetes. Furthermore, transgenic HPSE overexpression results in disappearance of HS, whereas expression of the core protein agrin remains unaltered. Our observations suggest that HPSE is involved in the pathogenesis of proteinuria in overt DNP by degradation of HS.     

Increased retinal image velocity after vestibular lesion

The vestibulo-ocular reflex stabilizes gaze during head movements by producing compensatory eye movements. Retinal image velocity (RIV) is defined as the difference between the eye and head velocities. The RIV of 20 vestibular schwannoma (VS) patients and 17 healthy controls was measured with a head autorotation test. The head autorotation test had a sensitivity of 80% and a specificity of 88%. The mean RIV (degree/second) +/- 95% confidence intervals of the VS patients in the 5 frequency bands of 1 to 5 Hz was respectively 4.8 (4.2 to 5.5), 11.5 (8.6 to 14.4), 21.7 (15.5 to 27.9), 25.2 (17.1 to 33.4), and 26.1 (13.1 to 39.1). The RIV of the VS patients was asymmetrically larger on the operated side (P<0.05) in the frequency band of 1 Hz. The mean RIV was significantly (P<0.05) larger in the VS patients than in the controls in the frequency bands of 1 to 4 Hz. The vestibulo-ocular reflex is inaccurate after VS surgery; but the inaccuracy may not lead to the occurrence of any symptoms.     

Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women

The aim of this study was to investigate the prevalence and correlates of peripheral arterial disease (PAD) in a population of osteoporotic postmenopausal women. The presence of PAD was assessed by ankle brachial index (ABI) in 345 ambulatory osteoporotic postmenopausal women, and in 360 community-based, age- and race-matched postmenopausal women with normal bone mineral density (BMD) (control group). PAD was detected in 63/345 (18.2%) osteoporotic women and in 14/360 (3.8%) control subjects (P < 0.0001). The mean ABI values were significantly lower in the osteoporosis group than in the control group (0.98 ± 0.09 vs. 1.04 ± 0.06, P < 0.0001). No difference in cardiovascular risk factors was observed between osteoporotic patients and controls, or between osteoporotic patients with and without PAD. Osteoporotic patients with PAD had lower femoral neck BMD T scores than those without PAD (−4.2 ± 0.7 vs. −2.3 ± 0.7, P < 0.0001). Only 4 PAD patients (5.1%) had intermittent claudication. In multivariate logistic regression analysis, factors independently associated with PAD within osteoporotic patients were lower femoral neck BMD T score (odds ratio (OR) = 0.20, 95% confidence interval (CI), 0.05–0.70, P = 0.01) and systolic blood pressure (OR = 1.02, 95% CI, 1.00–1.03, P = 0.01). This study shows for the first time an increased prevalence of PAD among osteoporotic postmenopausal women, with a lower femoral neck BMD T score being a significant independent predictor. The findings suggest that vascular status evaluation should be done in osteoporotic postmenopausal women in order to identify candidate patients for preventive and therapeutic cardiovascular interventions.     

Increased prevalence of colonic adenomas in patients with cystic fibrosis

BackgroundCystic fibrosis (CF) is the most common lethal genetic illness in the Caucasian population. Studies have shown that CF patients are at an elevated risk of developing colon cancer. Colonic adenomas are the precursors of colon cancer. This study aims to determine the prevalence of adenomas in patients with cystic fibrosis.MethodsAll patients were recruited prospectively at The Ottawa Hospital Cystic Fibrosis Clinic from 2010 through 2015. Baseline demographic and cystic fibrosis disease characteristics were collected from the clinic's CF patient database. Upon presentation at the endoscopy unit, and after a brief history and physical exam, a colonoscopy was performed. Polyps were resected if detected and sent to the pathology department for characterization. Findings were compared with a control group (pairing each CF patient with 5 age and sex-matched controls) of near-average risk patients who underwent a colonoscopy at the same center.ResultsOf the 33 patients that provided informed consent to participate in the study, 30 patients underwent colonoscopy and 13/30 (43.3%) were found to have colonic adenomas compared to 7 (4.7%) of the 150 control patients. The relative risk ratio for adenoma detection in a CF patient as compared to a matched control patient was 9.29 (95% CI 4.04–21.31), p < 0.01.ConclusionsColonic adenomas are more prevalent in CF patients compared to the general population. This study suggests the need for additional research to support recently published screening guidelines for CF patients.     

Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats

OBJECTIVE

Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats.

RESEARCH DESIGN AND METHODS

We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography.

RESULTS

Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm).

CONCLUSIONS

These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening.Diabetic macular edema (DME) is a leading cause of vision loss attributed to diabetes. The 14-year incidence of this disease in individuals with type 1 diabetes followed in the Wisconsin Epidemiologic Study of Diabetic Retinopathy was 26% (1), and the progression to clinically significant macular edema was associated with increasing retinopathy severity (2). Although intensive glycemic and blood pressure control can reduce the incidence of DME (3) once this condition develops, the treatment options include laser and vascular endothelial growth factor (VEGF)-targeted therapies, which provide substantial improvement in visual acuity for ~50% of patients with DME (4). Thus, additional treatment options for this disease are needed.DME is associated with a loss of blood-retinal barrier function, leading to increased diffusion of plasma components, thickening of the macula, and impairment in central vision (5,6). In addition to retinal thickening, increased retinal vascular permeability (RVP) alters the biochemical composition of the retinal interstitial fluid and the vitreous. Proteomic studies have begun to characterize the changes in the vitreous protein composition in people with diabetic retinopathy compared with nondiabetic subjects or diabetic subjects without diabetic retinopathy (7). We have previously reported an abundance of vasoactive plasma proteins, including components of the plasma kallikrein (PK)-kinin system (PKKS) in the vitreous of subjects with advanced diabetic retinopathy (7,8). These findings have suggested additional factors besides VEGF that may contribute to the decline in blood-retinal barrier integrity and vascular dysfunction in DME (9,10).Plasma prekallikrein (PPK) is an abundant serine protease zymogen in blood that is converted to its catalytically active form, PK, by factor XIIa (11), contributing to the innate inflammatory response and intrinsic coagulation cascades (12). The mechanisms that lead to the activation of this pathway in vivo include interactions with polyphosphates released from activated platelets and deficiency of C1 inhibitor (C1-INH), the primary physiological inhibitor of the PKKS (13,14). PK-mediated cleavage of high-molecular weight kininogen generates the nonapeptide bradykinin (BK), which activates the BK 2 (B2) receptor. Subsequent cleavage of BK by carboxypeptidases generates des-Arg⁹-BK, which activates the B1 receptor. Both B1 and B2 receptors are expressed by vascular, glial, and neuronal cell types, with the highest levels of retinal expression detected in the ganglion cell layer and inner and outer nuclear layers (15,16). Activation of B1 and B2 receptors causes vasodilation and increases vascular permeability (17–19). Previously, we have demonstrated that intravitreal injection of carbonic anhydrase-1 (CA-1) increased RVP and that this response was blocked by the inhibition of PK and by BK receptor antagonists (8). Recently, we reported that intravitreal injection of PK increased RVP in nondiabetic rats, and systemic administration of a small-molecule PK inhibitor, ASP-440, decreased RVP in rats subjected to angiotensin II (AngII)-induced hypertension (19). In the current study, we investigated the effects of PK on retinal vascular functions and retinal thickness in diabetic rats.     

Increased biliary cholesterol secretion in alloxan diabetic mice

Plasma and liver cholesterol levels and biliary cholesterol, phospholipid and bile acid concentrations were examined in normal and alloxan diabetic mice fed ordinary and 0.5 per cent cholesterol diets. The plasma and liver cholesterol levels markedly increased in the diabetic mice, and the cholesterol diet further increased the liver cholesterol level but not that in the plasma. The gallbladder bile weight increased in the diabetic mice, but not after the cholesterol diet. The biliary lipid concentrations markedly increased in the diabetic mice, and the increases of the cholesterol and phospholipids exceeded that of the bile acids, resulting in increases of the cholesterol molar concentration ratio (mole percent) and the lithogenic index. The cholesterol diet increased the biliary cholesterol concentration and slightly the phospholipid, but not the bile acids. Therefore, the cholesterol mole percent and the lithogenic index increased. Among the biliary bile acid composition, cholic and deoxycholic acids increased and beta-muricholic acid decreased in the diabetic mice, whereas the cholesterol diet feeding decreased cholic acid and increased chenodeoxycholic and alpha-muricholic acids. These data suggest that the mechanism of the increase of biliary cholesterol secretion in diabetic mice is different from that after cholesterol diet.     

Increased biliary cholesterol secretion in alloxan diabetic mice

Plasma and liver cholesterol levels and biliary cholesterol, phospholipid and bile acid concentrations were examined in normal and alloxan diabetic mice fed ordinary and 0.5 per cent cholesterol diets. The plasma and liver cholesterol levels markedly increased in the diabetic mice, and the cholesterol diet further increased the liver cholesterol level but not that in the plasma. The gallbladder bile weight increased in the diabetic mice, but not after the cholesterol diet. The biliary lipid concentrations markedly increased in the diabetic mice, and the increases of the cholesterol and phospholipids exceeded that of the bile acids, resulting in increases of the cholesterol molar concentration ratio (mole percent) and the lithogenic index. The cholesterol diet increased the biliary cholesterol concentration and slightly the phospholipid, but not the bile acids. Therefore, the cholesterol mole percent and the lithogenic index increased. Among the biliary bile acid composition, cholic and deoxycholic acids increased and β-muricholic acid decreased in the diabetic mice, whereas the cholesterol diet feeding decreased cholic acid and increased chenodeoxycholic and α-muricholic acids. These data suggest that the mechanism of the increase of biliary cholesterol secretion in diabetic mice is different from that after cholesterol diet.     

Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis

Summary

Indolent systemic mastocytosis (ISM) can trigger bone loss. However, the clinical relevance of different mast cell infiltration patterns for bone remains to be clarified. Here, we report increased bone turnover in individuals with ISM, and its extent is rather related to the type of mast cell distribution within the bone marrow than to the presence or absence of cutaneous manifestations.

Introduction

It is well established that ISM can trigger osteopenia or osteoporosis. However, neither the clinical relevance of the infiltration pattern of mast cells within the bone marrow nor the impact of the presence or absence of cutaneous mast cell infiltration has been elucidated.

Methods

We retrospectively analysed 300 cases with histologically proven ISM of the bone marrow and performed quantitative histomorphometry for a subgroup of 159 patients that did not receive any treatment before the biopsies were taken. Most importantly, since 66 % of the patients displayed ISM without the characteristic skin lesions, we were able to compare ISM with or without cutaneous manifestation.

Results

We found that both forms of ISM were not only characterized by a decreased trabecular bone mass but also by an increased number of osteoclasts and osteoblasts. Interestingly, when we analysed these data in relation to mast cell distribution, we found that the bone cell numbers in cases with mast cell granulomas were significantly increased compared to cases with diffuse mast cell distribution. Moreover, evidence of increased bone turnover was also found in 16 patients displaying osteosclerosis.

Conclusion

Based on the largest cohort of bone biopsies from patients with ISM analysed so far, we could demonstrate high bone turnover, more specifically increased osteoblast and osteoclast numbers and surface indices, as a cause of the skeletal changes. Moreover, the severity of the bone disease is presumably rather dependent on the amount of mast cells and their distribution within the bone marrow irrespective of the presence or absence of cutaneous involvement.     

Immunomorphological study of renal changes of diabetic individuals

The author carried out histological and immunofluorescence studies on 15 autopsied cases of diabetic glomerulosclerosis. In the nodular lesion of glomerulosclerosis IgG, C', IgM and fibrin were found in the glomeruli and at some sites also in the wall of the arterioles. In diffuse lesion of glomerulosclerosis IgG, C] and IgM were demonstrated on the glomerular basement membrane when the mesangium increased only slightly and thickening of the basement membrane of the glomeruli predominated. On the basis of her studies the author raises the possible immunological origin of diabetic glomerulosclerosis.     

长沙地区66772名体检人员尿石症患病情况调查

目的 探讨长沙地区人群尿石症患病率及发病主要危险因素.方法 采用成组病例对照研究方法,对66 772名体检者进行泌尿系B超、血生化、一般物理检查和性别、年龄等问卷调查.结果 该人群尿石症平均患病率为5.5%,男性结石患病率为6.9%,女性为3.4%.随年龄增加尿石症患病率呈上升趋势.肾结石比例最高,其次为输尿管结石、膀胱结石.结论 多因素分析提示:男性、年龄增加、口味偏咸、饮酒、吸烟、血尿酸高是尿石症危险因素.应综合防治,提倡合理膳食结构和保持良好生活习惯,多吃新鲜蔬菜和水果,可控制和降低泌尿系结石.

Abstract：

Objective To determine the prevalence and influencing factors of urinary calculi,to explore the interIrelationships between urinary stone disease and various risk and protective factors,to determine the potential implications for intervention and prevention in Changsha,and to evaluate the relative importance of each risk factor,with the objective of providing scientific guidelines for urinary calculi prevention and diagnosis. Methods A case-control study was designed,and 66,772 people were surveyed.Ultrasound examination,blood biochemistry,general physical examination,gender and age were asked in a questionnaire to determine a diagnosis of urolithiasis.By means of SPSS software a x2 tendency test and non-condition Logistic regression were conducted. Results A multivariate Logistic regression analyses was conducted.The final factors entered into the model were sex,age,profession,dietary habits,drinking habits,smoking and level of uric acid. Conclusions Hazard factors associated with urolithiasis are male gender,age,profession,dietary and drinking habits,smoking and level of uric acid.