Therapeutic potential of alpha-1 antitrypsin in human disease

Alpha-1 antitrypsin (AAT), an alpha globulin glycoprotein, is a member of the serine protease inhibitor (serpin) superfamily. The clinical significance of AAT is highlighted by AAT deficiency. Genetic deficiency of AAT can present as several neutrophilic diseases associated with emphysema, liver cirrhosis, panniculitis, and systemic vasculitis. Recently, animal and human studies have shown that AAT can control inflammatory, immunological, and tissue-protective responses. In addition, AAT treatment can prevent overt hyperglycemia, increase insulin secretion, and reduce cytokine-mediated apoptosis of pancreatic β-cells in diabetes. These multifunctional roles of AAT draw attention to the glycoprotein's therapeutic potential for many inflammatory and autoimmune diseases beyond AAT deficiency. As underlying mechanisms, recent studies have suggested the importance of serine protease inhibitory activity of AAT in obesity-associated insulin resistance, chronic obstructive pulmonary disease, and cystic fibrosis. In this review, we explore the multiple functions of AAT, in particular, the anti-inflammatory and serine protease inhibitory functions, and AAT's therapeutic potential in a variety of human diseases through published literature.

Gene Analysis of Thalassemia in Han and Dai Ethnic Childbearing-aged Population of Chinese Yunnan Province / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the common mutation spectrum of α- and β-thalassemia in Yunnan childbearing-aged population.</p><p><b>METHODS</b>The common mutation types of α- or β-globin genes were detected by multiple Gap-PCR and the PCR-reversed dot blotting, and the unknown mutation types were determined by DNA sequencing in DNA samples of hypochromic microcytic anemia patients and carriers who were confirmed to be positive by serologic screaning, then the mutation types of globin in Yunnan population were analyzed statistically.</p><p><b>RESULTS</b>A total of 40 kinds of mutation types were detected in 685 detected persons, among them the 3 commonest mutation types of α-globin genes were --(SEA)/αα (49.09%), -α(3.7)/αα (36.67%) and α(CS)α/αα (8.79%), the 3 commonest genetypes of β-globin gene were CD26(GAG>AAG)/N (43.78%), CD41-42(-CTTT)/N (20.1%) and CD17(AAG>TAG)/N (18.9%). There were 348 Han and 212 Dai ethnic persons in 685 cases, but their mutation of globin genes were different between these 2 ethnic groups. The results also showed that the gene mutation types were mostly concentrated in Dai ethnic individuals, since 28 of 38 detected α-β-thalassemia cases were Dai ethnic individuals.</p><p><b>CONCLUSION</b>The mutation spectrums of α- and β-globin genes in Yunnan childbearing-aged population are diverse and different from that in other areas of China.</p>

Urine alpha1-microglobulin is a better marker for early tubular dysfunction than beta2-microglobulin among tenofovir-exposed human immunodeficiency virus-infected men who have sex with men

Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir.Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-B-n-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy.Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p< 0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p= 0.024). There were no significant differences between groups for N-acetyl-β-n-glucosaminidase and albumin. In the longitudinal study, the median urinary alphat-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p= 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p> 0.05).Conclusion: Urinary alphat-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.

Investigating alpha-globin structural variants: a retrospective review of 135000 Brazilian individuals

Background: Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population. Methods: A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests. Results: Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia. Conclusion: The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

Clinical observation of the γ-globulin levels when Benign paroxysmal positional vertigo is attacking / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To observe the characteristics of serum protein in patients with benign paroxysmal positional vertigo (BPPV) during the symptomatic period.@*METHOD@#Fifty-five patients with BPPV and 58 control subjects were enrolled in the study. All the patients underwent the Dixe-Hallpike and Roll maneuver to confirm the type of BPPV. The average time of onset was (1.0 ± 0.8)days in the group of BPPV. The clinical features and the laboratory tests of serum protein electrophoresis, blood counts, and liver and kidney function were performed in both groups.@*RESULT@#The levels of serum albumin (Alb), α1 globulin, α2 globulin and β globulin of BPPV group did not differ statistically in the two groups (P > 0.05); The γ-globulin levels were significantly higher in patients with BPPV than in controls (P < 0.05).@*CONCLUSION@#The γ-globulin levels are increased when BPPV is attacking.

Urine alpha-1-microglobulin reliability in the diagnosis of pyelonephritis: a systematic review

Introduction:Pyelonephritis is known as kidney inflammation due to bacterial infection which should be diagnosed and treated promptly. In this article, we decided to systematically review the diagnostic value and reliability of evaluating urine excretion low molecular weight protein alpha-1-microglobulin [A1M]

Methods: PubMed and Scopus were searched for the relevant articles about the efficacy of urine alpha-1-micriglobulin assays in the diagnosis of pyelonephritis in children. The search strategy was microglobulin AND pyelonephritis. No language and date limitations were included in this review

Results: A total of 16 articles were retrieved from PubMed and 23 articles from Scopus. After studying the abstracts, only 5 articles were selected, which specifically studied the efficacy of alpha-1-micrglobulin in the diagnosis of pyelonephritis in children

Discussion: A1M is not an acute phase protein but its concentration alters in several clinical conditions

Conclusion: Evaluating the urine concentration of A1M is a noninvasive and cost effective strategy with the diagnostic capability for urinary tract disorders such as early recognition of tubular damages during pyelonephritis

External therapy of plasma cell mastitis by jiuyi powder using partial least-squares discriminant analysis: a safety analysis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the safety and the clinical value of external use of jiuyi Powder (JP) in treating plasma cell mastitis using partial least-squares discriminant analysis (PLSDA).</p><p><b>METHODS</b>Totally 50 patients with plasma cell mastitis treated by external use of JP were observed and biochemical examinations of blood and urine detected before application, at day 4 after application, at day 1 and 14 after discontinuation. Blood mercury and urinary mercury were detected before application, at day 1, 4, and 7 after application, at day 1 and 14 after discontinuation. Urinary mercury was also detected at 28 after discontinuation and 3 months after discontinuation. The information of wound, days of external application and the total dosage of external application were recorded before application, at day 1, 4, and 7 after application, as well as at day 1 after discontinuation. Then a discriminant model covering potential safety factors was set up by PLSDA after screening safety indices with important effects. The applicability of the model was assessed using area under ROC curve. Potential safety factors were assessed using variable importance in the projection (VIP).</p><p><b>RESULTS</b>Urinary β2-microglobulin (β2-MG), urinary N-acetyl-β-D-glucosaminidase (NAG), 24 h urinary protein, and urinary α1-microglobulin (α1-MG) were greatly affected by external use of JP in treating plasma cell mastitis. The accuracy rate of PLSDA discriminate model was 74. 00%. The sensitivity, specificity, and the area under ROC curve was 0. 7826, 0. 7037, and 0. 8084, respectively. Three factors with greater effect on the potential safety were screened as follows: pre-application volume of the sore cavity, days of external application, and the total dosage of external application.</p><p><b>CONCLUSIONS</b>PLSDA method could be used in analyzing bioinformation of clinical Chinese medicine. Urinary β2-MG and urinary NAG were two main safety monitoring indices. Days of external application and the total dosage of external application were main factors influencing blood mercury and urine mercury. A safety classification simulation model of treating plasma cell mastitis by external therapy of JP was established by the two factors, which could be used to assess the safety of external application of JP to some extent.</p>

Effects of tank operation on renal function of crews / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of harmful factors in tank cabins on renal function of tank crews.</p><p><b>METHODS</b>One hundred and fifty two tank crews as the observation group and 37 soldiers without tank environment exposure as control group were selected in the study. α1-microglobulin(α1-MG), β2-microglobulin(β2-MG), IgG, N-acetyl-β-glucosidase (NAG) and urinary albumin excretion rate (UAER) in morning and 24 h urine were measured.</p><p><b>RESULTS</b>Compared to the control group, the levels of α1-MG, β2-MG, NAG, UAER in observation group were increased significantly (P < 0.05). β2-MG, NAG, UAER of Soldiers with more than 50 motorized hours in observation group were significantly higher than those of control group (P < 0.05). β2-MG, NAG and UAER of soldiers divorced from tank occupation more than 3 years decreased to the normal levels. β2-MG of soldiers divorced from tank occupation more than 10 years was significantly higher than that of 6-10 years group.</p><p><b>CONCLUSION</b>Tank occupational exposure influences the renal function of tank crews but not to a degree of clinical kidney disease. The renal function of crews divorced from tank occupation may recover but dysfunction of renal tubular reabsorption still exists.</p>

Diagnostic value of renal function parameter detection of early renal damage in multiple myeloma / 中国实验血液学杂志

Renal damage is one of the most common complications and cause of death in patients with multiple myeloma (MM). The studies have pointed out that early renal impairment is risk factor for progress of this disease, timely diagnosis and prompt intervention therapy are very important to improve the prognosis and survival of MM patients. Therefore, the diagnosis of early renal damage is crucial for clinical treatment. The progress on detection of early renal damage parameters and their value are reviewed in this article.

Early prediction of acute kidney injury in infants and young children after cardiopulmonary bypass surgery / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the incidence of acute kidney injury (AKI) in infants and toddlers and evaluate the possibility of predicting AKI with urine neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), microalbumin (MA) and α1-microglobulin (α1-MG) after surgeries for congenital heart diseases with cardiopulmonary bypass (CPB).</p><p><b>METHOD</b>Fifty-eight children (ages ≤ 3 years) who had undergone surgery for congenital heart diseases with CPB were enrolled. Urinary samples were collected before and 4 h, 6 h, 12 h, 24 h post CPB to detect the concentration of NGAL, IL-18, NAG, MA and α1-MG.</p><p><b>RESULT</b>The AKI group had 29 cases, none AKI group also had 29 cases. Urinary concentration of NGAL 4, 6, and 12 h post CPB were significantly higher in AKI group (2820 µg/g, 905.7 µg/g, 76.1 µg/g separately) than in none AKI group (27.6 µg/g, 19.5 µg/g, 16.0 µg/g separately, P < 0.01). Urinary concentration of IL-18 4, 6, 12 and 24 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of NAG 4 h and 6 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.01). Urinary concentration of MA/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of α1-MG/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.01). All the five biomarkers had predictive abilities at 4-hour after surgery.</p><p><b>CONCLUSION</b>Urine biomarkers NGAL, IL-18, NAG, MA and α1-MG were valuable early predictors of AKI after CPB surgery.</p>

Effect of Hanfangji compound on proliferation of hepatic stellate cells and expressions of TTR, ITIH1 and SERPINF2 / 中国中药杂志

<p><b>OBJECTIVE</b>To observe and compare the effects of Hanfangji Compound and IFN-gamma on expressions of transthyretin (TTR) , inter-alpha inhibitor H1 (ITIH1) and serpin peptidase inhibitor clade F member 2 (SERPINF2) of hepatic stellate cells (HSC-T6).</p><p><b>METHOD</b>Hanfangji Compound and IFN-gammaof different concentrations were used in hepatic stellate cell-T6 (HSC-T6) for 48 h. Flow cytometer was used to detect the effects of Hanfangji Compound and IFN-gamma on HSC proliferation. RT-PCR method was adopted to detect mRNA expressions of TFR, ITIH1 and SERPINF2. TTR, ITIH1 and SERPINF2 secretions were detected by ELISA. The protein localizations of TTR, ITIH1 and SERPINF2 were examined by immune fluorescence. The protein expression of TfR and ITIHI were determined by Western blot.</p><p><b>RESULT</b>After Hanfangji Compound and IFN-gamma were adopted in HSC-T6, compared with the control group, the cell proliferation was inhibited obviously (P < 0. 05) , protein expressions of TTR, ITIH1 and SERPINF2 and mRNA expression increased significantly, with certain correlation with concentrations of Hanfangji Compound. The 2. 5 g L-I Hanfangji Compound group was superior to the IFN-gamma group (P <0. 05).</p><p><b>CONCLUSION</b>Hanfangji Compound can inhibit HSC proliferation, upregulated TTR, ITIH1 and SERPINF2 proteins and mRNA expression, which may be one of mechanisms of anti-hepatic fibrosis of Hanfangji Compound.</p>

Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with < 1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. alpha2-HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P < 0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.

Alpha1-microglobulin: a marker for early detection of tubular disorders in diabetic nephropathy

Tubular damage as suggested by tubular proteinuria is a recognised feature of glomerulonephritis. The objectives of the study were to compare the level of alpha-microglobulin in normal and diabetic patients, and also to find out whether the level of alpha-1 microglobulin could become a laboratory marker for tubulo-interstitial damage in diabetic nephropathy. Twenty-nine registered Type II diabetic patients of either sex were studied. The patients' age ranged from 41-50 years who were admitted in the medical ward, and those who visited the outdoor department of Sir Ganga Ram Hospital, Lahore were included in the study. The duration of study was one year from June 2006 to June 2007. Ten normal subjects with no history of diabetes were taken as controls. Blood samples and 24 hour urine samples of patients of all groups were collected. The levels of urinary protein and blood sugar were estimated by auto analyser. Proteinuria positive urinary samples were analysed by SDS-PAGE electrophoresis. The level of alpha-1 urinary protein was significantly increased in the group of diabetic patients as compared to the urinary protein level of normal subjects. Blood sugar level was also significantly increased in patients as compared to controls. Level of low molecular weight protein alpha-1 microglobulin showed an electrophoresis band of 28 Kda with an average volume of 6741.88 in the urine sample of patients. On the other hand, a very light, hardly recognizable band was observed in normal subjects. Urinary alpha-1 microglobulin provides a noninvasive and inexpensive diagnostic alternative for the diagnosis and monitoring of urinary tract disorders, i.e., early detection of tubular disorders of diabetic nephropathy. We propose that SDSPAGE electrophoresis is a comparatively inexpensive diagnostic approach to detect this marker in the urine sample

Identification of 2u-globulin and bound volatiles in the Indian common house rat (Rattus rattus)

The 2u-globulin (2u) is a pheromone carrier urinary protein believed to be relevant for sexual communication among rats and is characterized in laboratory rats. In the present study 17 kDa protein and the bound pheromones were characterized in a population of wild-type Indian common house rat (Rattus rattus). The protein was purified by two runs of Sephadex G-50 chromatography and analyzed with SDS-PAGE with MALDI-TOF/MS. The results of MASCOT search identified the protein as an 2u and suggested a role for binding pheromones. To confirm the protein bound volatiles, purified 2u was extracted with dichloromethane and volatile molecules were detected using of gas chromatography linked to mass spectrometry (GC-MS). 1-Chlorodecane was detected as the predominant compound and 2-methyl-N-phenyl-2-propenamide, hexadecane and 2,6,11-trimethyl decane as the minor compounds. The simple method of protein purification and the identification of bound volatiles may help in designing efficient pheromone-based rat traps.

Perfil eletroforético das proteínas séricas de serpentes Crotalus durissus terrificus (cascavel) criadas em cativeiro / Serum protein electrophoresis profile of the rattlesnake Crotalus durissus terrificus kept in captivity

As serpentes peçonhentas dos gêneros Bothrops e Crotalus têm sido mantidas em cativeiro visando à extração de venenos para a produção de imunobiológicos. O conhecimento da fisiologia desses animais e as alterações na concentração de proteínas e suas frações séricas são importantes para a identificação precoce de importantes enfermidades que cursam com estados de hipoproteinemia e hiperproteinemia. O objetivo do trabalho foi determinar a concentração de proteína total e o perfil eletroforético das proteínas séricas de serpentes Crotalus durissus terrificus (cascavel) criadas em cativeiro. Foram colhidas amostras de sangue da veia coccígea ventral de 21 serpentes adultas e sadias, divididas em dois grupos: Grupo 1 de 12 machos com peso médio de 588,89±193,55g, e Grupo 2 de nove fêmeas com peso médio de 708,33±194,04g. A proteína total sérica foi determinada pelo método de refratometria e a eletroforese em gel de agarose. Obtiveram-se valores da proteína total sérica (g/dL) de 4,51±0,50 para machos e de 4,82±0,72 para fêmeas, e para machos e fêmeas de 4,64±0,61. Foram identificadas pela eletroforese quatro frações protéicas (g/dL): albumina, a, b, g-globulinas e calculada a relação albumina:globulina. As serpentes fêmeas apresentaram maiores valores para as variáveis, albumina e para a relação albumina/globulina (AG) diferindo significativamente (P<0,05) do grupo de machos, porém sem significado clínico.

The poisonous snakes of the genera Crotalus and Bothrops have been kept in captivity with the purpose of extracting poison for the production of immunobiological. Knowledge of the physiology of these animals and serum proteins concentration changes are important for early identification of major diseases which lead to states of hypoproteinemia and hyperproteinemia. The objective was to determine the concentration of total protein and serum protein electrophoresis profile of Crotalus durissus terrificus (rattlesnake) in captivity. Blood samples were taken from the ventral coccygeal vein of 21 adult and healthy snakes divided into groups: Group 1 with 12 males, weighing in average 588.89±193.55g, and Group 2 with nine females, weighing in average 708.33±194.04g. The total serum concentration of protein was determined by the method of refractometry and agarose gel electrophoresis. The total protein values in the serum for females was 4.82±0.72, for males 4.51±0.50 and males and females 4.64±0.61, identified by four fractions (g/dL): albumin, a, b and g-globulin. Additionally the albumin/globulin ratio was calculated. The female snakes showed higher values for the variables, albumin and the albumin/globulin (AG) differed significantly (P<0.05) from the group of male snakes, but there was no clinical significance.

[Detection of unknown deletions in alpha globin genes in alpha thalassemia carriers using real-time PCR]

Alpha-thalassemia is one of the most prevalent hemoglobin disorders in the world and it is a common hereditary condition caused by deletion of one or more alpha-globin genes. Common alpha-thalassemia deletions like 3.7 kb, 4.2 kb, 20.5 kb and Med can be detected by Multiplex PCR. There are, however, some unknown deletions that can not be detected by the mentioned method or even by direct DNA sequencing. In the present study, Real-time PCR was used to determine the presence or absence of unknown deletions. Real-time PCR was performed using intercalating dye SYBR Green I and alpha1, alpha2 and CLCN7 genes were amplified. Data analysis was conducted using comparative threshold method [delta delta CT] for determination of Gene dosage of alpha1-globin and alpha2-globin genes. The results showed the ratio of 0.90 +/- 0.16 for normal individuals and the ratio of 0.32 +/- 0.15 for carrier samples with deletions. In addition, Melting curve analysis confirmed the specific amplification of target genes. The Real-time PCR assay is simple, rapid, and reliable. It can be applied for direct determination of unknown deletions in Alpha-thalassemia carriers

study of some genetic ameliorating factors in beta thalassemia

There are over 150 mutations affecting the beta globin gene that can lead to an altered expression of the gene and a decrease [beta [0]] or an absence [beta [+]] of beta globin production. The genes can be inherited in a homozygous or a heterozygous fashion. The result of inheritance of these genes can be diverse, ranging from beta thalassemia trait with no hematological disease to thalassemia major requiring repeated blood transfusions. There are co-inherited variables that can also influence the expression of this inheritance. Alpha gene deletion or the inheritance of the G gamma Xmn-1 gene sequence [C-T variation] at position -158 upstream of the G [gamma]-globin gene which is detectable by the restriction enzyme XmnI, are among these variables. The aim of this study is to clarify the effect of the above two variables as ameliorating factors in homozy-gous/double heterozygous beta thalassemia among a group of Egyptian thalassemic children. Thirty two cases of beta thalassemia were screened for common Mediterranean mutations [IVS1-110, 1-6,1-1, 11-745, codon 39, -87] alpha-gene deletions, and presence of G gamma Xmn-1 polymorphic site. As regards allele frequency, IVSI-6 showed the highest incidence [40.6%] followed by IVSI-110 [18.75%], IVSII-745 [12.5%], -87[9.37%], IVSI-1[3.12%] and codon 39 [0%]. 7 cases [21.87%] were uncharacterized as regards to the 6 screened mutations. The co-inheritance of a-thalassemia was found in 5 cases out of 32 cases [15.63%] and DNA polymorphism at -158 [C-T] of the gamma globin gene was demonstrated in 2/32 cases [6.25%]. Both variables ameliorated the severity of the disease either in the form of decreased frequency of blood transfusion or delay in age of presentation or an amelioration of clinical severity of a known severe allele

Identification of alpha-2u globulin in the rat preputial gland by MALDI-TOF analysis.

The low molecular mass proteins found in the pheromonal sources such as urine, saliva, glandular secretion etc have been reported as ligand carriers for the processes of chemocommunication in mammals. The preputial gland plays an important role in the production of olfactory signals for pheromonal communication. Thus, in the present study, alpha-2u globulin having molecular mass of 18 kDa has been identified in the preputial gland of Norway rat (Rattus norvegicus) by in-gel trypsin digestion and analyzing the resulting peptides by MALDI-TOF. Since preputial gland is one of the major pheromonal sources in rat, the results suggest that alpha-2u globulin might act as a carrier for hydrophobic odorants of preputial gland.

Effects of birth asphyxia or intrauterine distress on renal functions in newborns in the first week of life / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the renal function in newborns with birth asphyxia or intrauterine distress in the first week of life.</p><p><b>METHODS</b>Sixty full-term newborns born between June 2002 and February 2003 were assigned into three groups: Control group (healthy newborns), Intrauterine distress group (Apgar score > 7), and Birth asphyxia group without intrauterine distress (12 mild asphyxia and 8 severe asphyxia) (n=20 each). Urinary levels of alpha1-microglobulin (alpha1-MG), beta2-microglobulin (beta2-MG) and albumin (Alb) were detected by radioimmunoassay at 0-2, 3-4 and 6-7 days after birth.</p><p><b>RESULTS</b>The urinary levels of alpha1-MG, beta2-MG and Alb in the Asphyxia group were significantly higher than those in the Control group at all time points (P < 0.05), peaking at 3-4 days after birth. Statistically significant differences were found between the severely and mildly asphyxiated newborns for the urinary levels of alpha1-MG, beta2-MG and Alb at all time points (P < 0.05). There were no significant differences in the urinary levels of alpha1-MG, beta2-MG and Alb between the Intrauterine distress and the Control groups at each time point.</p><p><b>CONCLUSIONS</b>Birth asphyxia may lead to renal glomerular and tubular impairments and it is speculated that the most serious impairment occurs at the 3rd and 4th days of life. The severity of renal impairments is associated with the degree of asphyxia. The renal function of the newborn appears to be normal following intrauterine distress.</p>

Proteomic analysis of urinary protein markers for accurate prediction of diabetic kidney disorder.

AIM OF THE STUDY: Microalbuminuria is currently the only diagnostic tool available for early diagnosis of diabetic nephropathy. The test is based on immunological detection of small quantities of albumin in the urinary samples of diabetes patients. There are several limitations of the use of microalbuminuria as an index of renal function. It is therefore desirable to identify additional protein markers that would augment prediction of diabetic nephropathy. The aim of this study is to identify urinary protein markers for specific and more accurate prediction of nephropathy in diabetes patients. DESIGN: 100 registered Type II diabetic patients were studied. Abundant proteins of microalbuminuria positive urinary samples of these patients were analyzed by proteomics approaches of 2-Dimentional Gel Electrophoresis (2DGE) and mass spectrometry. RESULTS: 2-DGE analysis of the urine sample revealed four main proteins along with albumin in these samples. These were zinc alpha-2 glycoprotein, alpha-1 acid glycoprotein, alpha-1 microglobulin and IgG as identified by Matrix Assisted Laser Desorption Ionization-Tune of Flight (MALDI-ToF) and by western blot. Twenty control samples and three cases with microalbuminuria negative to positive transition does suggest the early and co-appearance of the markers with albumin. We have also analyzed full length spectrum of these samples by MALDI-ToF. CONCLUSION: Our study shows the presence of additional proteins in urine samples of microalbuminuria positive diabetes patients. These proteins can be used as markers for specific and accurate clinical analysis of Diabetic nephropathy. We propose a mass spectrometry based high throughput diagnostic approach to detect these markers in the urine sample.