Changes in Trace Elements During Early Stages of Chronic Kidney Disease in Type 2 Diabetic Patients

Trace elements can influence glucose metabolism and be related to oxidative stress in type 2 diabetes mellitus. Moreover, trace elements play important roles in the nephrotic complications of these patients. Nevertheless, few investigations have been made into the changes in the levels of trace elements in diabetic patients at various stages of chronic kidney disease (CKD). The aims of this present study were to determine the levels of some important trace elements in diabetic patients during the early stages of CKD and to identify the relationship between these elements and CKD progression in type 2 diabetic patients. One hundred and forty-eight type 2 diabetic patients with chronic kidney diseases were recruited into this study. The subjects were grouped into four stages (1, 2, 3a, 3b) of CKD, according to their urine protein levels and estimated glomerular filtration rates (eGFRs). The levels of serum zinc and iron exhibited a statistically significant decreasing trend (P trend?=?0.032 and 0.047, respectively) from stage 1 to stage 3b after adjustment for age, gender, smoking, alcohol consumption, education, hypertension, and body mass index. The other tested elements, including copper, magnesium, selenium, chromium, and manganese, did not display any significant trends upon proceeding from stage 1 to stage 3b. Thus, serum zinc and iron appear to be useful markers when evaluating the early progression of CKD in type 2 diabetic patients.     

Microtubule-Associated Protein 2 as an Early Indicator of Ischemia-Induced Neurodegeneration in the Gerbil Forebrain

Abstract: Microtubule-associated protein 2 (MAP-2) was studied in the gerbil hippocampus and striatum after transient ischemia. Western immunoblot analysis shows that there is a significant decrease of MAP-2 in the dorsolateral sector of the striatum and a slight decrease of MAP-2 in the CA1 region of the hippocampus 6–12 h after ischemia in the gerbil forebrain. The immunohistochemical staining pattern of MAP-2 in these two regions also shows a loss of immunostaining of MAP-2. In particular, a beaded MAP-2 immunostaining pattern at the apical dendritic region of the CA1 neurons of the hippocampus was found within 12 h after ischemia compared with the smooth dendritic immunostaining of MAP-2 in normal CA1 neurons. In vitro assays of MAP-2 degradation suggest that dendritic loss of immunoreactivity after ischemia seen on western blots may be due to calpain I degradation of MAP-2. Loss of MAP-2 in both the striatum and hippocampus was found to occur earlier than spectrin degradation by western blot analysis. These results suggest that loss of MAP-2 may participate in the initial phase of neuronal dysfunction and that dendritic breakdown may be a first sign of neurodegeneration.     

Head-butting as an Early Indicator of Reproductive Disinhibition in the Termite Zootermopsis nevadensis

In lower termites, functionally sterile larval helpers are totipotent—capable of becoming reproductively active with the loss of their colony’s king or queen. Full reproductive development may take several weeks, but initiation of this developmental response most likely occurs shortly after colony members detect when a reproductive-specific signal is missing. We investigated the early response of termite helpers to the removal of their king and queen in the basal termite species Zootermopsis nevadensis. Within 6–12 h after reproductives were removed, helpers displayed an increase in head-butting—a behavior associated with dominance in other termite species as well as in closely related roaches. The loss of just one reproductive, either the king or queen, was also sufficient to cause an increase in head-butting. We did not find evidence, however, that this response was sex-specific: males and females were equally likely to increase head-butting independent of the sex of the reproductive that was removed. Finally, we discovered that reproductive-specific compounds present on the cuticle of king and queen termites were also present in their feces, but the presence of the feces did not seem sufficient to inhibit the increased head-butting after the reproductives were removed. Collectively, these results indicate that termite workers readily detect the loss of reproductives in their colony and that they at least initially respond in a non sex-specific manner.     

Age-Related Alterations in the Biochemical and Functional Properties of the Bladder in Type 2 Diabetic GK Rats

Previous studies have demonstrated that experimental type 1 diabetes induced by streptozotocin causes alterations in the biochemical and functional properties of several receptor systems in the rat bladder. However, the exact mechanism involved in the pathophysiology of voiding dysfunction in type 2 diabetic patients is unknown. Because the GK rat is a widely accepted genetically determined rodent model for human type 2 diabetes, we investigated diabetes-induced changes in the bladder smooth muscle of the GK rats at several time points. Male GK rats and age-matched Wistar rats, as controls, were maintained for 4, 8, 16, and 32 weeks. Contractile responses to KCl, carbachol, ATP, and electrical field stimulation (EFS) were measured by using the isolated muscle bath techniques. Acetylcholine (ACh) release induced by EFS from bladder muscle strips was measured by using high-performance liquid chromatography coupled with a microdialysis procedure. Maximum contractile responses to carbachol and ATP, the release of ACh, and tissue sorbitol levels were similar in bladders from GK and control rats until 8 weeks of age. At 16 weeks of age, however, the contractile responses to carbachol and ATP, and tissue sorbitol levels were increased, and the EFS-induced ACh release was decreased in GK rats compared with controls. Although the maximum contractile responses to EFS were unchanged until 16 weeks of age, they were decreased in 32-week-old GK rats, compared with controls. Our data indicate the presence of age-related alterations in the biochemical and functional properties of the bladder in type 2 diabetic GK rats.     

Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility in Chickens

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Highlights

• •Quantitative proteomes of chicken seminal plasma associated with sperm motility.
• •High abundant acrosome and mitochondrial proteins were noted in LSM seminal plasma.
• •Decreased total antioxidant capacity was highlighted in seminal plasma of LSM.
• •Lack of membrane, acrosome and mitochondrial integrity and high ROS may induce LSM.

     

Evaluation of Prey-Stage Preference as an Indicator of Life-Style Type in Phytoseiid Mites

Discriminant analysis (DA) models were developed and applied to examine the use of prey-stage preference (Tetranychus urticae Koch egg versus larval prey) in the classification of phytoseiid mites into life-style types. Prey-stage preferences and developmental times when preying on T. urticae, and relative ovipositional rates on six food categories were determined for four phytoseiid species occurring on apple in central and eastern Oregon, USA: Galendromus flumenis (Chant), Galendromus occidentalis (Nesbitt), Metaseiulus citri (Garman and McGregor) and Typhlodromus caudiglans Schuster. In terms of all three aspects studied, the phytoseiid species showed a consistent polarization of G. occidentalis < or = G. flumenis < or = T. caudiglans < M. citri. Specifically, G. occidentalis ('The Dalles' strain) had a significant preference for eggs, G. flumenis had no preference, and T. caudiglans and M. citri had significant preferences for larvae; G. occidentalis had the shortest developmental time, followed by G. flumenis and T. caudiglans, while M. citri had the longest developmental time; and diet breadth was most narrow for G. occidentalis and progressively broader from G. flumenis, T. caudiglans through M. citri, which was able to sustain oviposition on the broadest range of prey and pollens. Species were classified somewhat differently depending on which traits were considered in a given DA. Prey-stage preference was not included as an indicator in the parsimonious DA model when all species and all traits were considered, but in general this trait performed well as an indicator alone (single-trait DA) and somewhat improved the classifications of multitrait discriminant analyses.     

西格列汀对早期2型糖尿病肾病患者肾功能的影响

目的:研究西格列汀对早期2型糖尿病肾病患者肾小球、肾小管标志性蛋白/酶的影响。方法:早期2型糖尿病肾病患者72例,随机数字表分为对照组36例、治疗组36例;两组均采用糖尿病饮食管理、运动治疗,在控制血糖、血脂、血压的基础上,治疗组给予磷酸西格列汀100 mg 1粒/次,1次/天,持续服药6月。观察治疗前、后两组血肌酐(Scr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、血脂、空腹血糖(FBG)、餐后2小时血糖(2 h PBG)、血清胱抑素-C(Cys-C)及24 h尿微量白蛋白(24 h UAE)、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)的变化。结果:治疗后,治疗组血脂、Hb A1c、FBG、2 h PBG较对照组明显下降,差异有显著性(P0.05)。两组患者24 h UAE、NAG、β2-MG和Cys-C较治疗前均下降,差异有显著性(P0.05);两组治疗后相比,差异具有统计学意义(P0.05)。结论:西格列汀可以有效控制早期DN患者的血糖水平,减少血清Cys-C、尿微量白蛋白水平,减轻肾小管损伤,有利于延缓DN的病程和进展。     

In Vitro NADH Oxidation as an Early Indicator for Growth Reduction in Spinach Exposed to H2S in the Ambient Air

H₂S reduced growth of spinach at levels higher than 0.075 µl/literand inhibited NADH oxidation by shoot extracts. Inhibition ofNADH oxidation was maximum after a 48-h exposure. Oxidationof NADH was equally sensitive to sulfide and cyanide. NADH oxidationshowed promise as an early indicator for growth reduction byH₂S. ¹Present address: Centre for Agrobiological Research, P.O. Box14, 6700 AA Wageningen, The Netherlands. (Received May 18, 1987; Accepted February 9, 1988)     

金黄地鼠胰岛素抵抗和糖尿病动物模型的建立

目的建立胰岛素抵抗和糖尿病动物模型。方法给金黄地鼠喂以高脂果糖饲料,部分给小剂量链脲菌素(30mg/kg)腹腔注射,以正常金黄地鼠作为对照,测定动物体重、空腹血糖、血脂、胰岛素水平,计算胰岛素敏感指数,并对肝脏、胰腺及主动脉弓组织进行形态学比较。结果金黄地鼠经高脂果糖喂养6周制成胰岛素抵抗、肥胖和脂质代谢紊乱的动物模型。再经小剂量一次性腹腔注射链脲菌素后,约80%的胰岛素抵抗和肥胖的金黄地鼠出现显性糖尿病。结论高脂果糖饲料结合小剂量链脲菌素腹腔注射可以制成胰岛素抵抗的2型糖尿病金黄地鼠模型。     

Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.     

The Association of Pioglitazone and Urinary Tract Disease in Type 2 Diabetic Taiwanese: Bladder Cancer and Chronic Kidney Disease

Objective

Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer.

Materials and Methods

In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease.

Results

Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4%) and 72 (0.2%), and for newly developed chronic kidney disease 245 (8.1%) and 663 (2.3%), respectively. Ever use of pioglitazone [1.59(1.32–1.91)], cumulative dose of pioglitazone <10,500 mg [1.69 (1.37–2.01)] and >10,500 mg [1.34 (1.04–1.73)], and duration of therapy <12 months [1.68 (1.36–2.08)] and >12 months [1.39 (1.09–1.76)] were associated with the development of chronic kidney disease.

Conclusions

There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.     

BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages

Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes Rb1 and p53, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved. Previously, we detected BKV DNA in the epithelial cells of benign and proliferative inflammatory atrophy ducts of cancerous prostate specimens. In the present report, we demonstrate that BKV is present at a much lower frequency in noncancerous prostates. Additionally, in normal prostates, T-antigen (TAg) expression is observed only in specimens harboring proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. We further demonstrate that the p53 gene from atrophic cells expressing TAg is wild type, whereas tumor cells expressing detectable nuclear p53 contain a mix of wild-type and mutant p53 genes, suggesting that TAg may inactivate p53 in the atrophic cells. Our results point toward a role for BKV in early prostate cancer progression.     

The Loudness Dependence of Auditory Evoked Potentials (LDAEP) as an Indicator of Serotonergic Dysfunction in Patients with Predominant Schizophrenic Negative Symptoms

Besides the influence of dopaminergic neurotransmission on negative symptoms in schizophrenia, there is evidence that alterations of serotonin (5-HT) system functioning also play a crucial role in the pathophysiology of these disabling symptoms. From post mortem and genetic studies on patients with negative symptoms a 5-HT dysfunction is documented. In addition atypical neuroleptics and some antidepressants improve negative symptoms via serotonergic action. So far no research has been done to directly clarify the association between the serotonergic functioning and the extent of negative symptoms. Therefore, we examined the status of brain 5-HT level in negative symptoms in schizophrenia by means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP provides a well established and non-invasive in vivo marker of the central 5-HT activity. We investigated 13 patients with schizophrenia with predominant negative symptoms treated with atypical neuroleptics and 13 healthy age and gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component was evaluated by dipole source analysis and single electrode estimation at Cz. Psychopathological parameters, nicotine use and medication were assessed to control for additional influencing factors. Schizophrenic patients showed significantly higher LDAEP in both hemispheres than controls. Furthermore, the LDAEP in the right hemisphere in patients was related to higher scores in scales assessing negative symptoms. A relationship with positive symptoms was not found. These data might suggest a diminished central serotonergic neurotransmission in patients with predominant negative symptoms.     

Alpha-Fetoprotein in Retina and Lens of the Human Eye at Early Stages of Prenatal Development

The presence of alpha-fetoprotein (AFP) was shown in the retina and lens of the human fetal eye at different stages of prenatal development. PCR analysis revealed AFP mRNA neither in the retina nor in the lens, whereas in the fetal liver (control) AFP mRNA was found to be expressed. The data obtained indicate that AFP is not synthesized in retinal and lens cells of the human fetal eye but is imported from elsewhere to be taken up by these cells. The presence of AFP in the retina and lens implies its involvement in early morphogenesis and differentiation of these ocular tissues during prenatal human development.     

Protein Bodies at Early Stages of Development in High Lysine Mutant Notch-2 and Parent NP-113 Barley

In barley parent NP-113, endospermic protein bodies originate on rough endoplasmic reticulum, either as electron transluscent vesicles or as very small, spherical, electron dense protein bodies, These are translocated to vacuoles tor enlargement and subsequent storage, Endospermic protein bodies of Notch-2 high lysine mutant are either vacuolar, or confined to distended cisternae of smooth endoplasmic reticulum. Vacuolar protein bodies are of two types one, flocculent, which loosely fill up almost the entire vacuolar space; two, spherical, relatively compact and granular, Protein bodies, confined to smooth endoplasmic reticulum are small, spherical, electron dense or electron transluscent, These protein bodies fuse to form electron dense proteinaceous masses which are deposited in the cytosol due to disruption of the confining smooth endoplasmic reticulum.