Biochemical Features (biochemical + feature)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Nitrogen-assimilating enzymes in land plants and algae: phylogenic and physiological perspectives

PHYSIOLOGIA PLANTARUM, Issue 1 2002
Ritsuko Inokuchi
An important biochemical feature of autotrophs, land plants and algae, is their incorporation of inorganic nitrogen, nitrate and ammonium, into the carbon skeleton. Nitrate and ammonium are converted into glutamine and glutamate to produce organic nitrogen compounds, for example proteins and nucleic acids. Ammonium is not only a preferred nitrogen source but also a key metabolite, situated at the junction between carbon metabolism and nitrogen assimilation, because nitrogen compounds can choose an alternative pathway according to the stages of their growth and environmental conditions. The enzymes involved in the reactions are nitrate reductase (EC 1.6.6.1-2), nitrite reductase (EC 1.7.7.1), glutamine synthetase (EC 6.3.1.2), glutamate synthase (EC 1.4.1.13-14, 1.4.7.1), glutamate dehydrogenase (EC 1.4.1.2-4), aspartate aminotransferase (EC 2.6.1.1), asparagine synthase (EC 6.3.5.4), and phosphoenolpyruvate carboxylase (EC 4.1.1.31). Many of these enzymes exist in multiple forms in different subcellular compartments within different organs and tissues, and play sometimes overlapping and sometimes distinctive roles. Here, we summarize the biochemical characteristics and the physiological roles of these enzymes. We also analyse the molecular evolution of glutamine synthetase, glutamate synthase and glutamate dehydrogenase, and discuss the evolutionary relationships of these three enzymes. [source]


Insights into the acute cerebral metabolic changes associated with childhood diabetes

DIABETIC MEDICINE, Issue 5 2005
F. J. Cameron
Abstract Aims Type 1 diabetes is a prevalent chronic disease in childhood with the commonest single cause of death being cerebral oedema in the context of diabetic ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may result in vulnerability to neuronal injury remains unknown. The aim of this study was to analyse the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) brain data from eight children with diabetes following acute presentation with hyperglycaemia with or without ketoacidosis, to determine the nature and timing of any alterations in cerebral structure and metabolism. Methods This study used MRI and MRS to investigate regional cerebral abnormalities in a small series of diabetic patients with and without DKA. Changes were compared with the clinical and biochemical features of the patients studied. Results Our small series of patients all demonstrated abnormal signal changes in the frontal region on fluid attenuated inversion recovery (FLAIR) MR imaging, suggestive of oedema, and spectroscopic abnormalities of increased taurine, myoinositol and glucose levels. The MR abnormalities varied in severity but did not correlate with any clinical or biochemical parameters. Conclusions These changes indicate that many diabetic children, particularly at presentation, may have alterations in cerebral metabolism with implications for the pathogenesis and treatment of the cerebral complications of DKA. In addition, our findings suggest that increased taurine may be one of the important differentiating factors in the response of the brain of diabetic children to DKA that may reflect an increase in their vulnerability to cerebral oedema compared with diabetic adults. [source]


Isoform-specific quantification of metallothionein in the terrestrial gastropod Helix pomatia.

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2004

Abstract The two function-specific metallothionein (MT) isoforms characterized from the midgut gland and mantle tissue of Helix pomatia differ substantially in their metal-binding preferences, as well as molecular and biochemical features. These differences make them potential candidates for biomarker studies based on a differential, isoform-specific approach. To prove this hypothesis, induction experiments with two metals (Cd and Cu) that are normally bound by the two isoforms were compared with a range of organic chemicals and physical stressors under laboratory conditions to test the responsiveness of the two isoforms to the stressors applied. In addition, field studies were conducted with Roman snails and substrate samples collected from different metal-contaminated sites in Austria to test the suitability of the two isoforms as biomarkers under field conditions. The results of these combined laboratory and field studies confirmed the validity of the biomarker approach with the two metal- and tissue-specific isoforms. It is demonstrated that the Cd-binding MT specifically and exclusively responds to Cd exposure by increasing concentrations, whereas the Cu-binding MT isoform decreases in its concentration upon exposure to physical stress (X-ray irradiation and cold). This suggests researchers should adopt, under certain preconditions, a dual biomarker approach by combining the simultaneous quantification of Cd-MT concentrations in the midgut gland as a biomarker for Cd pollution and of Cu-MT concentration in the mantle as a biomarker for the impairment of snails by additional physical stressors. [source]


ATP-dependent modulation and autophosphorylation of rapeseed 2-Cys peroxiredoxin

FEBS JOURNAL, Issue 7 2008
Martin Aran
2-Cys peroxiredoxins (2-Cys Prx) are ubiquitous thiol-containing peroxidases that have been implicated in antioxidant defense and signal transduction. Although their biochemical features have been extensively studied, little is known about the mechanisms that link the redox activity and non-redox processes. Here we report that the concerted action of a nucleoside triphosphate and Mg2+ on rapeseed 2-Cys Prx reversibly impairs the peroxidase activity and promotes the formation of high molecular mass species. Using protein intrinsic fluorescence in the analysis of site-directed mutants, we demonstrate that ATP quenches the emission intensity of Trp179, a residue close to the conserved Cys175. More importantly, we found that ATP facilitates the autophosphorylation of 2-Cys Prx when the protein is successively reduced with thiol-bearing compounds and oxidized with hydroperoxides or quinones. MS analyses reveal that 2-Cys Prx incorporates the phosphoryl group into the Cys175 residue yielding the sulfinic-phosphoryl [Prx-(Cys175)-SO2PO32,] and the sulfonic-phosphoryl [Prx-(Cys175)-SO3PO32,] anhydrides. Hence, the functional coupling between ATP and 2-Cys Prx gives novel insights into not only the removal of reactive oxygen species, but also mechanisms that link the energy status of the cell and the oxidation of cysteine residues. [source]


The Influence of Lactobacillus brevis on Ornithine Decarboxylase Activity and Polyamine Profiles in Helicobacter pylori -Infected Gastric Mucosa

HELICOBACTER, Issue 2 2004
Michele Linsalata
ABSTRACT Background., Functional probiotics may prevent Helicobacter pylori infection, and some evidence suggests that they also possess antitumor properties. Lactobacillus brevis (CD2) is a functional Lactobacillus strain with peculiar biochemical features, essentially related to the activity of arginine deiminase. This enzyme catalyzes the catabolism of arginine and affects the biosynthesis of polyamines (putrescine, spermidine, and spermine). Polyamines are polycations found in high concentrations in both normal and neoplastic cells. Our aims were: 1, to assess whether oral administration of L. brevis (CD2) affects H. pylori survival in the human gastric mucosa; 2, to evaluate the effects of L. brevis (CD2) on polyamine biosynthesis in gastric biopsies from H. pylori- positive patients. Materials and Methods., For 3 weeks before endoscopy, 22 H. pylori- positive dyspeptic patients randomly received (ratio 1 : 1) high oral doses of L. brevis (CD2) or placebo. Before and after treatment, H. pylori infection was determined by urea breath test (UBT). In gastric biopsies, ornithine decarboxylase activity and polyamine levels were, respectively, evaluated by a radiometric technique and high-pressure liquid chromatography (HPLC). Results.,L. brevis (CD2) treatment did not eradicate H. pylori. However, a reduction in the UBT delta values occurred, suggesting a decrease in intragastric bacterial load. Significantly, L. brevis (CD2) induced a decrease in gastric ornithine decarboxylase activity and polyamine levels. Conclusions., Our data support the hypothesis that L. brevis (CD2) treatment decreases H. pylori colonization, thus reducing polyamine biosynthesis. Alternatively, the arginine deiminase activity following L. brevis (CD2) administration might cause arginine deficiency, preventing polyamine generation from gastric cells. [source]


Histologic and biochemical changes during the evolution of chronic rejection of liver allografts

HEPATOLOGY, Issue 3 2002
Desley A. H. Neil
Criteria for histologic diagnosis of chronic rejection (CR) are based on changes seen late in the disease process that are likely to be irreversible and unresponsive to treatment. Changes occurring during the evolution of CR are less clearly defined. The serial biopsy specimens, failed allografts, and biochemical profiles of 28 patients who underwent retransplantation for CR were examined with the aim of identifying histologic and biochemical features that were present during the early stages of CR. For each case, a point of acute deterioration in liver function tests (LFTs) was identified ("start time" [ST]) that subsequently progressed to graft failure. Biopsy specimens before, at the time of ("start biopsy" [SB]), and after the ST were assessed histologically, and findings were correlated with the biochemical changes. CR resulted from acute rejection (AR) that did not resolve. Centrilobular necroinflammation (CLNI) associated with an elevated aspartate transaminase (AST) level and portal tract features of AR were present at the start. Portal AR features resolved, CLNI persisted, AST level remained elevated, and bilirubin and alkaline phosphatase levels progressively increased throughout the evolution of CR. Portal tracts also showed a loss of small arterial and bile duct branches, with arterial loss occurring early and bile duct loss as a later progressive lesion. Foam cell arteriopathy was rarely seen in needle biopsy specimens. In conclusion, findings from this study may help identify patients at risk of progressing to graft loss from CR at a stage when the disease process is potentially reversible and amenable to treatment. [source]


Laboratory diagnosis of variant Creutzfeldt,Jakob disease

HISTOPATHOLOGY, Issue 1 2000
J W Ironside
The neuropathological and biochemical features of 33 cases of variant Creutzfeldt,Jakob disease (vCJD) diagnosed up to the end of 1998 are analysed in relation to the 646 cases of suspected CJD referred to the CJD Surveillance Unit laboratory from 1990 to 1998. Morphological studies of the central nervous system, lymphoid tissues and other organs were accompanied by immunocytochemistry; Western blot analysis of PrPRES was performed on frozen brain tissue. The findings were analysed in relation to clinical and genetic data. The pathology of vCJD showed morphological and immunocytochemical characteristics distinct from other cases of CJD. PrP accumulation was widespread in lymphoid tissues in vCJD, but was not identified in other non-neural tissues. PrPRES accumulation in vCJD brain tissue showed a uniform glycotype pattern distinct from sporadic CJD. All analysed cases of vCJD were methionine homozygotes at codon 129 of the PrP gene. No evidence currently exists to suggest that cases of CJD diagnosed in individuals who are MV or VV at codon 129 of the PrP gene represent ,human bovine spongiform encaphalopathy (BSE)'. Continued surveillance is required to further investigate this possibility, with the need to investigate autopsy tissues from suspected cases by histological and biochemical techniques. [source]


Evaluation of management of Graves' disease in District General Hospital: achievement of consensus guidelines

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2005
S. Dasgupta
Summary The management of Graves' disease in a District General Hospital was audited. A local care pathway was designed, which was inclusive of diagnosis, treatment and follow-up. This was then compared with consensus guidelines proposed by the Royal College of Physicians. Forty-six patients with Graves' disease attended the endocrine clinic. The diagnosis was based on clinical and biochemical features of autoimmune thyrotoxicosis, a raised thyroid-stimulating hormone receptor antibody (TRAB) and a diffusely increased uptake in thyroid technetium scan. They were treated for 18 months with antithyroid medications, which was subsequently discontinued provided satisfactory euthyroid state was achieved. Patients were followed up to assess remission and relapse status. The audit suggested that care pathway was in keeping with the guidelines. A few excess TRAB tests were requested. The relapse rate was 42% in our series and one-third of them (33%) chose to continue medical therapy. [source]


S100A6 (calcyclin) deficiency induces senescence-like changes in cell cycle, morphology and functional characteristics of mouse NIH 3T3 fibroblasts

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010
omnicki, ukasz P. S
Abstract S100A6 (calcyclin) is a calcium binding protein with two EF-hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non-transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by ,-galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function. J. Cell. Biochem. 109: 576,584, 2010. © 2009 Wiley-Liss, Inc. [source]


Primary hyperparathyroidism: new concepts in clinical, densitometric and biochemical features

JOURNAL OF INTERNAL MEDICINE, Issue 1 2005
J. P. BILEZIKIAN
Abstract. Primary hyperparathyroidism (PHPT) is characterized most commonly now as an asymptomatic disorder with hypercalcaemia and elevated levels of parathyroid hormone (PTH). The elevation in PTH is detected by both the standard immunoradiometric assays (IRMA) and a more recent IRMA that detects only the 1,84 full-length PTH molecule. The serum calcium concentration is usually <1 mg dL,1 above normal. Recently, another variant of PHPT (normocalcaemic PHPT) has been described in which the serum calcium is normal but the serum PTH is elevated, in the absence of any secondary cause for PTH elevation. Although usually sporadic, PHPT also occurs in inherited syndromes. Skeletal manifestations are appreciated by densitometry showing a typical pattern in which cancellous bone of the lumbar spine is reasonably well preserved whilst the cortical bone of the distal third of the radius is preferentially reduced. Although reduced in incidence, renal stones remain the most common overt complication of PHPT. Other organs are theoretical targets of PHPT such as the neurobehavioural axis and the cardiovascular system. Vitamin D looms as an important determinant of the activity of the PHPT state. The 2002 NIH Workshop on asymptomatic PHPT has led to revised guidelines to help doctors determine who is best advised to have parathyroid surgery and who can be safely followed without surgery. New information about the natural history of PHPT in those who did not undergo surgery has helped to define more precisely who is at-risk for complications. At the NIH workshop, a number of items were highlighted for further investigation such as pharmacological approaches to controlling hypercalcaemia, elevated PTH levels and maintaining bone density. [source]


Bartter's Syndrome in Pregnancy: A Case Report and Review

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2000
Dr. Ivy C. F. Li
Abstract Bartter's syndrome is a rare renal tubular disorder, involving juxtaglomerular cells hyperplasia, characterized by normotensive hyper-reninism and secondary hyperaldosteronism, marked renal loss of potassium and profound hypokalaemia. Both clinical and biochemical features are heterogeneous, ranging from the incidental finding in an asymptomatic patient to marked clinical features of hypokalaemia. Inheritance is likely to be an autosomal recessive. We present a case of Bartter's syndrome complicating pregnancy in a Chinese woman. We documented an increasing demand for potassium supplement during pregnancy which stabilized by mid-trimester. The absence of pregnancy complications such as polyhydramnios indicated that the fetus was unlikely to be affected by the condition. [source]


New established melanoma cell lines: genetic and biochemical characterization of cell division cycle

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2003
A Vozza
ABSTRACT Background Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. Objective On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. Results The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. Conclusions Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene. [source]


Comparative study on the proteolytic activities and storage globulins in seeds of Theobroma grandiflorum (Willd ex Spreng) Schum and Theobroma bicolor Humb Bonpl, in relation to their potential to generate chocolate-like aroma

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 7 2004
Christoph Reisdorff
Abstract The cocoa relatives T grandiflorum (cupuaçu) and T bicolor (macambo) are promising crop plants for sustainable agroforestry in the Amazon region of South America. The market for cupuaçu is expanding since the fruit flesh is utilised by the foodstuffs industry. Attempts to commercialise chocolate-like wares from the seeds have failed so far because of unreliable product quality. It is not known whether this is due to an insufficient aroma potential of cupuaçu seeds. We therefore investigated the proteolytic enzymes and the seed storage globulins which are both decisive for the formation of aroma precursors in cocoa. We found that the activities of the aspartic endopeptidase and the carboxypeptidase in T bicolor and T grandiflorum differed slightly from those in cocoa. The specificity of the carboxypeptidase for hydrophobic amino acids was quite similar across the three species, while the optimal pH of the T grandiflorum enzyme was lower than that of the other species. The qualitative and quantitative differences between the globulins indicate a lower maximum yield of aroma precursors in T grandiflorum and a higher maximum yield of aroma precursors in T bicolor, compared to cocoa. We conclude that the quality of chocolate-like products made from the studied cocoa relatives can be improved by adapting fermentation procedures to particular biochemical features of these seeds. Copyright © 2004 Society of Chemical Industry [source]


An integrated analysis of the genome of the hyperthermophilic archaeon Pyrococcus abyssi

MOLECULAR MICROBIOLOGY, Issue 6 2003
Georges N. Cohen
Summary The hyperthermophilic euryarchaeon Pyrococcus abyssi and the related species Pyrococcus furiosus and Pyrococcus horikoshii, whose genomes have been completely sequenced, are presently used as model organisms in different laboratories to study archaeal DNA replication and gene expression and to develop genetic tools for hyperthermophiles. We have performed an extensive re-annotation of the genome of P. abyssi to obtain an integrated view of its phylogeny, molecular biology and physiology. Many new functions are predicted for both informational and operational proteins. Moreover, several candidate genes have been identified that might encode missing links in key metabolic pathways, some of which have unique biochemical features. The great majority of Pyrococcus proteins are typical archaeal proteins and their phylogenetic pattern agrees with its position near the root of the archaeal tree. However, proteins probably from bacterial origin, including some from mesophilic bacteria, are also present in the P. abyssi genome. [source]


Laboratory Forum: Experimental Models of Peyronie's Disease.

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009
Implications for New Therapies
ABSTRACT Introduction., Despite its high prevalence and impact on the quality of life of patients, and that it is an excellent model for the study of fibrotic processes, Peyronie's disease (PD) is an orphan disease in biomedical research. The development of animal and cell culture models has advanced substantially the understanding of its molecular and cellular pathology and the proposal of new therapies. Aim., To review the literature pertaining to the use of these models for the study of PD. Methods., PubMed search conducted from the first report of an animal model for PD. Results., This model, based on the finding that transforming growth factor ,1 (TGF,1) is overexpressed in the PD plaque, consists on the injection of TGF,1 into the tunica albuginea of the rat. This leads to a PD-like plaque retaining many of the histological and biochemical features of human PD. Another rat model, based on the hypothesis that the PD plaque arises from trauma to the penis, causing fibrinogen extravasation that initiates as fibrin a fibrotic response, consists on injection of fibrin into the tunica. The cell culture model is based on the demonstration that myofibroblasts are abundant in the human PD plaque. Conclusions., These models have: (i) clarified the role of microtrauma, myofibroblasts, and oxidative stress in plaque development; (ii) demonstrated that this tissue is under sustained turnover by fibrotic and antifibrotic mechanisms; (iii) showed the interplay of collagenolytic and fibrinolytic systems and their inhibitors; (iv) detected an endogenous antifibrotic process consisting of the expression of inducible nitric oxide synthase that counteracts oxidative stress, collagen synthesis, and myofibroblast generation; (v) characterized the antifibrotic effects of chronic treatment with phosphodiesterase type 5 (PDE5) inhibitors; (vi) discovered the cytogenetic instability of PD cells and alterations in their gene expression; and (vii) detected stem cells in the tunica albuginea with a potential role in fibrosis and ossification. Gonzalez-Cadavid NF, and Rajfer J. Experimental models of peyronie's disease. Implications for new therapies. J Sex Med 2009;6:303,313. [source]


Recurrent Primary Biliary Cirrhosis After Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010
M. G. Silveira
Recurrent primary biliary cirrhosis (PBC) is an important clinical outcome after liver transplantation (LT) in selected patients. Prevalence rates for recurrent PBC (rPBC) reported by individual LT programs range between 9% and 35%. The diagnostic hallmark of rPBC is histologic identification of granulomatous changes. Clinical and biochemical features are frequently absent with rPBC and cannot be used alone for diagnostic purposes. Some of the risk factors of rPBC may include recipient factors such as age, gender, HLA status and immunosuppression, as well as donor factors such as age, gender and ischemic time, although controversy exists. Most patients have early stage disease at the time of diagnosis, and there may be a role for therapy with ursodeoxycholic acid. While short- and medium-term outcomes remain favorable, especially if compared to patients transplanted for other indications, continued follow-up may identify reduced long-term graft and patient survival. [source]


In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 8 2007
Christian S. Haas
Objective Interleukin-13 (IL-13) is a pleiotropic cytokine that can affect vessel formation, an important component of the rheumatoid arthritis (RA) synovial tissue pannus. The purpose of this study was to use a gene therapy approach to investigate the role of IL-13 in angiogenesis in vivo, using a rat adjuvant-induced arthritis model of RA. Methods Ankle joints of female rats were injected preventatively with an adenovirus vector containing human IL-13 (AxCAIL-13), a control vector with no insert (AxCANI), or phosphate buffered saline (PBS). Joints were harvested at the peak of arthritis, and histologic and biochemical features were evaluated. Results AxCAIL-13,treated joint homogenates had lower hemoglobin levels, suggesting reduced joint vascularity, and both endothelial cell migration and tube formation were significantly inhibited (P < 0.05). Similarly, AxCAIL-13 inhibited capillary sprouting in the rat aortic ring assay and vessel growth in the Matrigel plug in vivo assay. IL-13 gene delivery resulted in up-regulation and association of phosphorylated ERK-1/2 and protein kinase C,/,II, suggesting a novel pathway in IL-13,mediated angiostasis. The angiostatic effect of AxCAIL-13 was associated with down-regulation of proangiogenic cytokines (IL-18, cytokine-induced neutrophil chemoattractant 1/CXCL1, lipopolysaccharide-induced CXC chemokine/CXCL5) and up-regulation of the angiogenesis inhibitor endostatin. The expression and activity of matrix metalloproteinases 2 and 9, which participate in angiogenesis, was impaired in response to IL-13 as compared with AxCANI and PBS treatment. Conclusion Our findings support a role for IL-13 as an in vivo antiangiogenic factor and provide a rationale for its use in RA to control pathologic neovascularization. [source]


Nitrite reduction: a ubiquitous function from a pre-aerobic past

BIOESSAYS, Issue 8 2009
Francesca Cutruzzolà
Abstract In eukaryotes, small amounts of nitrite confer cytoprotection against ischemia/reperfusion-related tissue damage in vivo, possibly via reduction to nitric oxide (NO) and inhibition of mitochondrial function. Several hemeproteins are involved in this protective mechanism, starting with deoxyhemoglobin, which is capable of reducing nitrite. In facultative aerobic bacteria, such as Pseudomonas aeruginosa, nitrite is reduced to NO by specialized heme-containing enzymes called cd1 nitrite reductases. The details of their catalytic mechanism are summarized below, together with a hypothesis on the biological role of the unusual d1 -heme, which, in the reduced state, shows unique properties (very high affinity for nitrite and exceptionally fast dissociation of NO). Our results support the idea that the nitrite-based reactions of contemporary eukaryotes are a vestige of earlier bacterial biochemical pathways. The evidence that nitrite reductase activities of enzymes with different cellular roles and biochemical features still exist today highlights the importance of nitrite in cellular homeostasis. [source]


Female pattern hair loss, sebum excretion and the end-organ response to androgens

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006
M.P. Birch
Summary Background, Although female pattern hair loss can be a feature of hyperandrogenism, many women with hair loss show no clinical or biochemical features of androgen excess. It is possible that hair loss in nonhyperandrogenic women is due to a high level of response to androgens by scalp hair follicles. In this study we explored this idea using sebum excretion as a marker of the cutaneous end-organ response to androgens. Objectives, To test the hypothesis that hair loss in nonhyperandrogenic women is due to an increased cutaneous end-organ response to androgens. Methods, We studied 100 women, 41 with female pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp hair loss) and 30 subjects without hair problems. We measured hair density on the frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and body mass index (BMI). Results, The mean FAI was significantly raised in hirsute women compared with nonhirsute women (P < 0·001), but there was no difference in FAI levels between nonhirsute women with and without hair loss. The mean BMI was also significantly elevated in hirsute women (P < 0·01) but there was no difference in BMI between nonhirsute women with and without hair loss. The mean sebum excretion was higher in hirsute women than nonhirsute women but the difference was not statistically significant. There was no difference in sebum excretion between nonhirsute women with and without hair loss. There was no correlation between hair density and sebum excretion. Conclusions, Our results show that sebum excretion is not elevated in women with female pattern hair loss. This may indicate that different androgen-response pathways operate in controlling hair growth and sebum excretion. The alternative explanation is that nonandrogenic mechanisms are involved in mediating hair loss in some women. [source]


Early therapeutic intervention in females with Fabry disease?

ACTA PAEDIATRICA, Issue 2008
Derralynn A Hughes
Abstract Anderson,Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of ,-galactosidase A. The subsequent accumulation of globotriaosylceramide (Gb3) in cells and tissues of the body has multisystemic effects and significantly impacts upon quality of life and survival of individuals with this condition. In general, Anderson,Fabry disease is more severe in male patients; however, despite X-linkage, females may develop severe signs and symptoms of the disease, although there is considerable phenotypic heterogeneity, which correlates most closely with age. Histological analyses of biopsies have shown evidence of Gb3 storage in the kidney and heart in female patients. Gb3 levels are also elevated in the urine of females, although plasma Gb3 levels are not reliably elevated. The efficacy of enzyme replacement therapy (ERT) with recombinant human ,-galactosidase A has been demonstrated in females in a clinical trial and in observational studies, including those using data from outcome surveys. Benefits include a reduction in left ventricular mass, stabilization of renal function and improvements in pain and quality of life. Conclusion: If early intervention with ERT in females is to be advocated, it is necessary to demonstrate not only that females with Anderson,Fabry disease have clinical and biochemical features of ,-galactosidase A deficiency and respond to ERT, but also that early intervention prevents the onset of the later manifestations of the disorder. Any strategy for early therapy should also balance future advantages against any impact on quality of life. [source]