bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Salivary Stimulation on Erosion of Human and Bovine Enamel Subjected or Not to Subsequent Abrasion: An in situ/ex vivo Study
Authors: Rios D. , Honório H.M. , Magalhães A.C. , Delbem A.C.B. , Machado M.A.A.M. , Silva S.M.B. , Buzalaf M.A.R.
Published: May 2006

This in situ/ex vivo study evaluated whether saliva stimulated by chewing gum could prevent or reduce the wear and the percent change in microhardness (%SMH) of bovine and human enamel submitted to erosion followed by brushing abrasion immediately or after 1 h. During 2 experimental 7-day crossover phases, 9 previously selected volunteers wore intraoral palatal devices, with 12 enamel specimens (6 human and 6 bovine). In the first phase, the volunteers immersed the device for 5 min in 150 ml of cola drink, 4 times per day (at 8, 12, 16 and 20 h). Immediately after the immersions, no treatment was performed in 4 specimens, 4 other specimens were immediately brushed (0 min) using a fluoride dentifrice, and the device was replaced into the mouth. After 60 min, the remaining 4 specimens were brushed. In the second phase, the procedures were repeated, but after the immersions, the volunteers stimulated the salivary flow rate by chewing a sugar-free gum for 30 min. Changes in wear and %SMH were measured. ANOVA and Tukey’s test showed statistical differences (p < 0.05) for the following comparisons. The chewing gum promoted less wear and %SMH. A decreasing %SMH and an increasing enamel wear were observed in the following conditions: erosion only, 60 min and 0 min. The human enamel presented greater %SMH and less wear compared to bovine enamel. The data suggest that the salivary stimulation after an erosive or erosive/abrasive attack can reduce the dental wear and the %SMH.
Influence of Growth Rate and Length on Fluoride Detection in Human Nails
Authors: Buzalaf M.A.R. , Pessan J.P. , Alves K.M.R.P.
Published: May 2006

This study aimed to determine the lag time between increased fluoride (F) intake and F detection in human nails, as well as the influence of nails growth rate and length on this. Ten 20- to 35-year-old volunteers received 1.8 mg F daily, for 30 days. Nail growth rate and length were determined for all fingernails and toenails. Nail samples were collected at the beginning of the study and every 2 weeks (15 collections in all) and F concentrations were determined. The growth rate was statistically higher in fingernails than in toenails. No statistically significant differences were observed between right and left sides. Growth rate was significantly greater for big toenails than for the other toenails, but this pattern was not found for fingernails. The estimated mean lag times for F detection in fingernails and toenails were 101 and 123 days, respectively. An apparent increase in fingernail F concentrations was observed 84 days after the beginning of the study, although this was not statistically different from baseline. For toenails, statistically significant increases in F concentration in relation to baseline were observed 112 and 140 days after increased F ingestion. These increases occurred within the 95% confidence intervals for the calculated mean lag time for fluoride detection in nails. Considering the large amount of sample provided by the big toenails, together with their faster growth rate, as well as the fact that toenails are less prone to environmental contamination, our data suggest that big toenails are more suitable biomarkers of fluoride intake.
Acid Susceptibility of Arrested Enamel Lesions: In situ Study
Authors: Maltz M. , Scherer S.C. , Parolo C.C.F. , Jardim J.J.
Published: May 2006

Arrested lesions are more resistant to a new cariogenic challenge, but the degree of surface rehardening needed to achieve this is unknown. The aim of this in situ study was to analyze the acid susceptibilityof newly formed and arrested enamel lesions with known arrestment period and surface microhardness. Six individuals wore an oral appliance with human enamel blocks for 3 periods: (1) 21 days of demineralization due to plaque accumulation and cariogenic challenge, 4 blocks/person (nonfluoride dentifrice); (2) 75 days of arrestment, brushing with fluoride dentifrice, 2 blocks/person; (3) 21 days of demineralization, 5 blocks/person: 1 sound block, 2 demineralized blocks and 2 demineralized and arrested blocks (nonfluoride dentifrice). After period 1, all blocks showed a dull whitish surface characteristic of active, noncavitated lesions. After arrestment, the surfaces assumed a shiny and smooth aspect. The Knoop hardness number (KHN, mean ± SD) of the sound blocks was 307.6 ± 15.0. After period 1, microhardness decreased significantly to 162.6 ± 33.5 KHN (p < 0.001). The microhardness of subsequently arrested lesions (279.8 ± 23.1 KHN) was significantly greater than after demineralization, but lower than that of sound enamel. Arrested enamel did not show a decrease in microhardness when subjected to a new cariogenic challenge and after the same cariogenic challenge showed similar microhardness to sound enamel. The results showed that, although noncavitated lesions probably take years to reach microhardness levels like sound enamel, this does not imply that special care, in addition to the ones normally given to sound tooth surfaces, is necessary.
Occurrence of the Family Bifidobacteriaceae in Human Dental Caries and Plaque
Authors: Modesto M. , Biavati B. , Mattarelli P.
Published: May 2006

Despite the constant presence of members of Bifidobacteriaceae in the human oral cavity, few studies of their occurrence in this habitat have been made. The presence and the distribution in human plaque and dental caries of Bifidobacterium dentium, Scardovia inopinata and Parascardovia denticolens, all belonging to the family Bifidobacteriaceae, were studied. The identification to species level was based on morphological and growth type features, fermentation tests, polyacrylamide gel electrophoresis of the soluble proteins and DNA-DNA homology. The three species, isolated on propionic acid trypticase phytone yeast extract medium, were present in 13 out of 19 and in 11 out of 15 subjects examined for dental caries and plaque, respectively. S. inopinata was the species most frequently isolated in dental caries, whereas B. dentium was more numerous in dental plaque.The prevalence of P. denticolens was similar in the two habitats. In conclusion, the prevalence of bifidobacteria species (B. dentium, P. denticolens, S. inopinata) in relation to non-bifidobacteria isolates was significantly different in caries versus plaque samples (p < 0.0001; χ2 test).
Epidemiology of Psoriasis
Authors: Schäfer Torsten
Published: May 2006

According to population-based European studies, 2–3% of the population are affected by psoriasis. However, commonly accepted and validated diagnostic criteria are lacking. Psoriasis patients, compared to those with other dermatological disorders, are among those who suffer the highest impact on their quality of life, and this affection is comparable to other common diseases. Several lifestyle factors including alcohol and smoking have been associated with psoriasis. There is also evidence for associations with other diseases including cancer. Treatment of psoriasis engenders considerable costs, which should always be taken into account together with the relevant clinical outcome parameters. Prevention of psoriasis is crucial, as in the case of other common chronic diseases where causative treatments are lacking, but has barely been studied.
Generalized Mucinosis in a Patient with Erythroderma
Authors: Fujimura Taku , Okuyama Ryuhei , Nakagawa Satoshi , Terui Tadashi , Aiba Setsuya
Published: May 2006

We describe an 81-year-old Japanese patient with erythroderma overlapping with widespread and symmetrical deposits of mucin in the upper dermis. Clinically, the mucinous lesions on the nape and upper trunk were localized papular mucinosis. Histologically, there was a perivascular infiltrate of lymphohistiocytic cells mingled with plasma cells in the upper dermis but no sclerosis. Immunohistochemical staining revealed that more than 90% of these infiltrating plasma cells produced immunoglobulin λ-chain. Both the erythroderma and generalized mucinosis responded to topical steroid and PUVA therapy. To the best of our knowledge, this is the first case of erythroderma accompanied by generalized mucinosis.
Wegener’s Granulomatosis of the Penis: Genital Presentation of Systemic Disease
Authors: Al Rajabi Wajdi , Venturini Marina , Sala Raffaella , Calzavara-Pinton Piergiacomo
Published: May 2006

Wegener’s granulomatosis (WG) is a systemic vasculitis of small and medium-size vessels, mostly affecting the respiratory tract and the kidneys, although any organ may be involved. This case concerns a 50-year-old man in whom WG caused an asymptomatic erosion on the glans penis and prepuce. Histological examination showed an unspecific inflammatory infiltrate. Four months later, a sudden and simultaneous onset of lesions of the upper respiratory tract and kidneys occurred, as well as peripheral neuropathy, polyarthritis, positivity of antineutrophilic cytoplasmic antibodies and its proteinase 3 subset. Histological examination of a nodular lesion on the left leg showed leukocytoclastic vasculitis of small and medium-size vessels, suggesting the diagnosis of WG. Cases in which isolated unspecific erosive lesions of the penis are the only symptoms of WG have been seen in only 4 other patients so far, and a correct diagnosis was only possible due to a careful follow-up study.
Sodium Thiosulphate as a Promising Therapeutic Option to Treat Calciphylaxis
Authors: Meissner M. , Bauer R. , Beier C. , Betz C. , Wolter M. , Kaufmann R. , Gille J.
Published: May 2006

A 35-year-old haemodialysis-dependent woman with chronic renal failure developed large, very painful necrotic ulcers and necrosis on the thighs, buttocks and the abdomen with signs of fast progression. The skin biopsy specimens showed a broad necrosis of the epidermis and thrombosed dermal vessels with focal calcium deposits within the wall. In addi tion, laboratory findings presented an increased product of serum calcium and phosphate concentrations. Thus, we diagnosed calciphylaxis on the basis of clinical, biochemical and histopathological criteria. We initiated a therapy in which our patient was treated with intravenous sodium thiosulphate 3 times weekly. Already after 2 weeks of treatment, no new lesions were detectable and there was a dramatic pain relief. In the following 4 weeks, a successive decline of the ulcers and the healing of individual tissue defects could be seen. Four months after the start of the therapy, the patient underwent successful renal transplantation. Thus, the intravenous therapy of calciphylaxis with sodium thiosulphate might be a new effective alternative in the treatment of this life-threatening disease.
A Case of Epidermolysis Bullosa Acquisita with Autoantibody to Anti-p200 Pemphigoid Antigen and Exfoliative Esophagitis
Authors: Yamada Tomoko , Suzuki Masayuki , Koike Yumiko , Kida Kinuyo , Murata Satoru , Ishii Norito , Hashimoto Takashi , Ohtsuki Mamitaro
Published: May 2006

Background: Some cases of a subepidermal blistering disease associated with autoantibodies to more than two antigens have been reported. Observation: A 52-year-old Japanese woman had pruritic blisters on almost the whole body as well as erosive lesions in the oral cavity and esophagus. A histological finding was subepidermal bullae. Direct immunofluorescence (IF) revealed a linear deposition of IgG, IgM and C3 at the epidermal basement membrane zone (BMZ). Indirect IF using human skin split by 1 M NaCl as a substrate showed IgG antibody reactive with the dermal side. By immunoblot analysis using normal human dermal extract, the 200-kDa and 290-kDa bands were detected. Indirect IF did not show any anti-BMZ antibody activity, when using the skin of the patient with recessive dystrophic epidermolysis bullosa as a substrate. Conclusion: We regarded our case as epidermolysis bullosa acquisita with autoantibody to anti-p200 pemphigoid antigen. This is the second case in the literature associated with autoantibodies to these two antigens.
Neuroprotection – STAIR-Way to the Future?
Authors: Shuaib Ashfaq
Published: May 2006

Preclinical testing of putative neuroprotective agents for the treatment of acute ischaemic stroke is critical in assessing their therapeutic potential. Guidelines on how preclinical development of neuroprotectants should be performed were lacking until the Stroke Therapy Academic Industry Roundtable (STAIR) published their recommendations based on lessons from previous failed clinical trials of neuroprotective agents. The STAIR recommendations seek to improve the quality of preclinical research and to ensure that the data generated will enable the selection of those agents most suitable for progression from the laboratory into clinical trials. NXY-059 is a novel free-radical trapping neuroprotectant that is being investigated for the treatment of acute ischaemic stroke. Its preclinical development has closely adhered to the stringent STAIR criteria. Data from independent studies using rodent models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) show that NXY-059 reduces infarct volume, improves neurological functioning and has an extended therapeutic window (≧4 h) compared with other agents in late-stage clinical development to date. A key difference in its development compared with previous neuroprotectants is that, in accordance with STAIR criteria, its neuroprotective efficacy has been confirmed in large animal models of pMCAO. These studies in marmosets clearly demonstrate that NXY-059 reduces the functional disability arising from cerebral ischaemia. As functional outcome (rather than infarct volume) is the relevant outcome against which stroke drugs are evaluated in clinical trials, this finding is both important and encouraging. NXY-059 is currently being evaluated in Phase III trials.
Snake C-Type Lectin-Like Proteins and Platelet Receptors
Authors: Clemetson Kenneth J. , Lu Qiumin , Clemetson Jeannine M.
Published: May 2006

Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with α and β subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, α2β1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin α2β1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.
Scratching below the Surface: Wound Healing and Alanine Mutagenesis Provide Unique Insights into Interactions between Eristostatin, Platelets and Melanoma Cells
Authors: McLane Mary Ann , Zhang Xiaoming , Tian Jing , Zelinskas Claire , Srivastava Apoorva , Hensley Brett , Paquette-Straub Carrie
Published: May 2006

To study the molecular mechanism of the disintegrin eristostatin, cellular functional studies were performed using ten recombinant alanine mutants. ADP-induced platelet aggregation revealed critical contributions of seven residues within the ‘RGD loop’ (R24, R27, G28, N31) and C-terminus (W47, N48, G49) of this disintegrin. Using an in vitro scratch wound healing assay, four human melanoma cell lines yielded similar results when exposed to wildtype eristostatin. All eristostatin-treated cells healed less of the wounded area than control conditions. This phenomenon was reproduced when using fibronectin as the matrix. C8161 cells showed significant delay in wound closure with the N-terminal mutant P4A but not with R24A or G28A. Evidence from our laboratory and others suggests neither alpha IIb, alpha 4 nor alpha 5 integrins are directly involved in eristostatin’s interactions. Eristostatin did not affect the number of melanoma cells in culture after 24 h or the development of apoptosis. However, phosphorylation studies performed after these melanoma cells were exposed to eristostatin revealed changes in several tyrosine phosphorylated molecules.
Hemextin AB Complex – A Snake Venom Anticoagulant Protein Complex That Inhibits Factor VIIa Activity
Authors: Banerjee Yajnavalka , Mizuguchi Jun , Iwanaga Sadaaki , Kini R. Manjunatha
Published: May 2006

Snake venom is a veritable gold mine of bioactive molecules, capable of binding to a wide variety of pharmacological targets, including the blood coagulation cascade. Here, we report the isolation and characterization of two synergistically acting anticoagulant three-finger proteins, hemextin A and hemextin B, from the venom of Hemachatus haemachatus (African Ringhals cobra). Hemextin A but not hemextin B exhibits mild anticoagulant activity. However, hemextin B interacts with hemextin A and forms a complex (hemextin AB complex), and synergistically enhances its anticoagulant potency. Prothrombin time assay showed that these two proteins form a 1:1 complex. Using a ‘a dissection approach’, we found that hemextins A and AB complex prolong clotting by inhibiting extrinsic tenase activity. Further studies showed that hemextin AB complex potently inhibits the proteolytic activity of factor VIIa (FVIIa) and its complexes. Kinetic studies showed that hemextin AB complex is a non-competitive inhibitor of FVIIa-soluble tissue factor proteolytic activity with a Ki of 25 nM. Hemextin AB complex is the first reported natural inhibitor of FVIIa that does not require either tissue factor or factor Xa scaffold to mediate its inhibitory activity. Molecular interactions of hemextin AB complex with FVIIa/tissue factor-FVIIa may provide a new paradigm in the search for anticoagulants inhibiting the initiation of blood coagulation.
Antihemostatic Molecules from Saliva of Blood-Feeding Arthropods
Authors: Champagne Donald E.
Published: May 2006

The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Each time this trait evolves, novel solutions to the problem posed by vertebrate hemostasis are generated. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Molecular approaches (termed ‘sialomics’) to characterize the full inventory of mRNAs transcribed in salivary glands have revealed a surprising level of complexity within a single species. Multiple salivary proteins may be directed against each component of hemostasis, resulting in both redundancy and in some cases cooperative interactions between antihemostatic proteins, as in the case of the Rhodnius prolixus apyrase (which hydrolyzes ADP) and Rhodnius platelet aggregation inhibitor 1 (which sequesters ADP). The complexity and redundancy of saliva ensures an efficient blood meal for the arthropod, but it also provides a diverse array of novel antihemostatic molecules for the pharmacologist.
Brief Informant Screening Test for Mild Cognitive Impairment and Early Alzheimer’s Disease
Authors: Li Minglei , Ng Tze Pin , Kua Ee Heok , Ko Soo Meng
Published: May 2006

Background/Aims: Recent research has attempted combinations of instruments to improve screening accuracy for mild cognitive impairment (MCI) and early Alzheimer’s disease (AD). We compared Mini-Mental State Examination (MMSE), Immediate and Delayed Recall (Logical Memory I and II; LM-I and LM-II, respectively), a single-item informant report of memory problem (IRMP), and a four-item Instrumental Activities of Daily Living (4IADL) scale, and combinations of these tests. Method: The tests were administered together with Clinical Dementia Rating (CDR) to subjects who were cognitively intact (CDR = 0, n = 88), and with diagnoses of MCI (CDR = 0.5, n = 37) and early AD (CDR = 1–2, n = 19). Results: Screening accuracy (receiver operating characteristic area under curve, AUC) for identifying MCI or MCI-AD was lowest for MMSE (AUC 67.6% for MCI or 77.9% for MCI-AD), and better for IRMP (79.5 or 83.2%), 4IADL (76.9 or 84.7%), LM-I (81.2 or 87.1%) and LM-II (86.1 or 90.8%). Combining IRMP, 4IADL and LM-II was most accurate (AUC 91.7% for MCI or 94.5% for MCI-AD); sensitivity: 86.5 or 89.3%; specificity: 86.4 or 88.6%. However, combining IRMP and 4IADL gave nearly as good accuracy (AUC 87.2 or 91.6%); sensitivity: 86.5 or 85.7%; specificity: 79.5 or 85.2%. Conclusion: A brief instrument combining an IRMP and 4IADL items is potentially useful in screening for MCI and early AD.
Is Mortality Increased in Mildly Cognitively Impaired Individuals?
Authors: Guehne Uta , Angermeyer Matthias C. , Riedel-Heller Steffi
Published: May 2006

Numerous studies have focused on the effect of mild cognitive impairment in elderly people. However, the impact of mild cognitive impairment on mortality has rarely been considered so far. This paper reviews recent work on mild cognitive impairment and its mortality risk. Relevant articles were identified by a systematic search of the literature published since 1990 using the databases PubMed, Web of Science and PSYNDEXplus, bibliographies of articles identified and of earlier reviews. Those studies were considered which predominantly included persons aged 65 and over and which relied on population-based samples. Thus only eight studies could be identified. In general, the relative risk (RR) for subjects with mild cognitive impairment according to different concepts in comparison to non-affected persons varies from 1.0 to 1.9. However, only few studies are available, and a comparison of the literature is problematic, due to variations in criteria and methodology.
Normal Range of Calcitonin in Children Measured by a Chemiluminescent Two-Site Immunometric Assay
Authors: Verga Uberta , Morpurgo Paola S. , Vaghi Ivan , Radetti Giorgio , Beck-Peccoz Paolo
Published: May 2006

Calcitonin (CT) assay is of considerable importance in the routine evaluation of thyroid nodules and for screening and follow-up of patients with medullary thyroid carcinoma and their relatives. Aim of this study was to assess the reference ranges for CT levels in healthy children and to evaluate possible differences in CT levels between sex and age. Serum CT levels were measured by a commercially available two-site chemiluminescence immunometric assay (sensitivity = 0.2 pg/ml). The ILMA recognizes the mature monomeric form of CT. We evaluated a cohort of 125 healthy children and compared these results with those from 98 healthy adult men and women. The ranges for human CT in children were <0.2–11.7 pg/ml and <0.2–17 pg/ml for female and male, respectively. No gender differences were observed in children population, though higher CT levels were observed in males. Serum CT levels did not correlate with age. Adult female had statistically significant lower CT levels than female children (p ≤0.05). In the adult population, males showed levels of CT higher than females. In conclusion, this study provide normal range for children population at different age with a sensible two-site chemiluminescent immunoassay. Since the normal range of serum CT levels is wider in healthy children than in adults, these data suggest establishing different normal range values in different age groups.
Complete Cytoreduction Combined with Early Postoperative Intraperitoneal Chemotherapy for Ovarian Carcinosarcoma
Authors: Xanthoulis A. , Mirelis Charalambos , Markakidis Sotirios , Bougioukas Ioannis , Bekiaridou Konstantina , Tsalkidou Evanthia , Zafeiropoulos Georgios , Tentes Antonios-Apostolos K.
Published: May 2006

Background/Aims: The purpose of the study is to report two long-term survivors with ovarian carcinosarcomas, which are rare intrapelvic malignancies with unfavorable prognosis. Methods: Two middle-aged women with palpable abdominal tumors underwent complete cytoreductive surgery and no macroscopic tumor was left behind. Early postoperative intraperitoneal chemotherapy with doxorubicin was used as an adjuvant treatment. Results: The patients are disease-free 2 and 3 years, respectively after the initial therapy. Conclusion: Complete cytoreduction combined with early postoperative intraperitoneal chemotherapy seems to be an effective treatment for ovarian carcinosarcoma with peritoneal spread. Further studies are required to define the value of intraperitoneal chemotherapy in ovarian carcinosarcoma.
NAD Dependent 11β-Hydroxysteroid Dehydrogenase Activity in Human Endometrium and Endometrial Tumors
Authors: Manolis Tsatsas , Lee Yi-Chun , Temkin Sarah , Hellman Mira , Nacharaju Vijaya L. , Abulafia Ovadia
Published: May 2006

Background: The isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2, regulated by ovarian steroids, catalyze the interconversion of glucocorticoids and their 11-keto metabolites. The role of these enzymes in malignancies of human endometrium is unknown. We compare NAD dependent 11β-HSD (type 2) activity levels among normal human endometrium and endometrial carcinomas of differing grades and histologies. Methods: NAD dependent 11β-HSD activity was determined in endometrial tissue obtained from patients undergoing hysterectomy for benign or malignant disease (endometroid, serous and carcinosarcomas). Student’s t test was utilized with p < 0.05 considered significant. Data are presented as mean ± SD. Results: NAD dependent 11β-HSD activity was present in all endometrial samples. The activities were 0.61± 0.27 in normal (n = 9), 0.43 ± 0.29 in endometrioid endometrial carcinoma (n = 14), 0.50 ± 0.26 in uterine serous carcinoma (n = 6) and 0.25 ± 0.37 in carcinosarcomas (n = 9). NAD dependent 11β-HSD activity was lower in the carcinosarcoma group as compared to normal endometrial tissue (p = 0.03). Conclusions: NAD dependent type 2 11β-HSD activity was demonstrated in all normal and endometrial tumors. Enzyme activity in endometroid and uterine serious carcinoma tumors was similar to enzyme activity in normal endometrium. In contrast, carcinosarcomas show significantly lower enzyme activity compared to normal tissue.
Genomewide Oligonucleotide Microarray Analysis on Placentae of Pre-Eclamptic Pregnancies
Authors: Zhou Rongrong , Zhu Qianyong , Wang Yahui , Ren Yonghong , Zhang Liang , Zhou Yuxiang
Published: May 2006

Objective: Human placentae from normal and pre-eclamptic pregnancies were evaluated for possible changes in gene expression by microarray analysis to uncover new clues for the research of the etiology of pre-eclampsia. Methods: Placentae from five normal pregnancies and five pregnancies complicated by pre-eclampsia were collected. mRNA levels of five pre-eclamptic placentae were examined using genome-wide 70-mer oligonucleotide microarrays (CapitalBio, Beijing, China) in comparison with the pooled control consisting of total RNA from five normotensive placentae. Results: Ninety-six genes were found consistently down- or up-regulated in at least four pre-eclamptic samples. Most of them were related to an imbalance of reactive oxygen metabolites in placenta, abnormal trophoblast invasion, disorders of lipoprotein metabolism and signal transduction, or some that have been reported to have close correlation to the pathology of pre-eclampsia. The microarray data were also confirmed by the measurement of real-time PCR. Conclusion: DNA microarray is a high throughput and time-saving method to monitor altered gene expression. The results could provide interesting clues to the etiology of pre-eclampsia and lead to further studies in a more targeted fashion.
Clinicopathological Characteristics and Outcome of Adult Patients with Hematuria and/or Proteinuria Found during Routine Examination
Authors: Shen Peicheng , Ding Xiaoqiang , Ten Jie , Ji Jun , Zou Jianzhou , Fang Yi
Published: May 2006

Background: Patients with hematuria and/or proteinuria found during routine examination are commonly encountered. To define the clinicopathological characteristics and outcome of these patients, 142 patients with definite pathological diagnosis were studied retrospectively.Methods: All the 142 patients were divided into three groups: pure hematuria (HU, n = 13), concomitant hematuria and proteinuria (HUPU, n = 79), and proteinuria alone (PU, n = 50). Results: At the time of renal biopsy, 26% of the patients had renal insufficiency and 48% of the patients had hypertension. Pathologically, IgA nephropathy (n = 67) was the most common. A total of 51 patients were enrolled into the follow-up group. Finally, urinary abnormalities disappeared in 18% of the patients, 22% of HU developed proteinuria, 21% of HUPU and 23% of PU appeared to have a distinct increase of proteinuria, and 15% of PU developed hematuria. Seven patients with normal blood pressure before became hypertensive and 6% of the patients with normal renal function initially developed renal insufficiency. The renal outcome was associated with proteinuria and tubulointerstitial lesions. Conclusion: Because renal pathologic change does not always coincide with clinical manifestations, patients with hematuria and/or proteinuria found during routine examination do not necessarily imply a favorable outcome, so renal biopsy is quite important. Besides, early treatment and careful follow-up are helpful in these patients.
Brain Natriuretic Peptide and N-Terminal proBNP in Chronic Haemodialysis Patients
Authors: Racek Jaroslav , Králová Hana , Trefil Ladislav , Rajdl Daniel , Eiselt Jaromír
Published: May 2006

Background: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are released into circulation as a result of congestive heart failure (HF). As HF and water overload are frequent complications in haemodialysis (HD) patients, we decided to study the levels of BNP and NT-proBNP and their changes during HD. Methods: BNP and NT-proBNP levels were determined in 94 HD patients before and after a regular 4-h HD. We followed changes in these peptides during HD depending on age, sex, HF (NYHA classification and left ventricular ejection fraction [LVEF]), duration on HD, presence of hypertension, coronary artery disease, type of membrane used for HD [low-flux (LFx) or high-flux (HFx)] and body mass change during HD. Furthermore, patients´ basic medication and creatinine levels and presence of diabetes mellitus were monitored. Results: Respectively,94% and 100% of the patients had pre-dialysis concentrations of BNP and NT-proBNP above the cut-off values for HF. The marker levels correlated significantly both before and after HD (r = 0.903 and 0.888, respectively, p < 0.001). BNP levels significantly decreased (p < 0.0001), whereas NT-proBNP significantly increased (p < 0.0001) during HD on LFx membranes. HD on HFx membranes caused greater decrease of BNP (compared to LFx membranes, p < 0.001), but also a decrease of NT-proBNP (p < 0.001).We did not find any significant differences in marker levels for HF and non-HF patients (NYHA classification). However, both peptides reached higher levels in the group with LVEF ≤50% (p < 0.001 for both peptides). Body mass change during HD negatively correlated only with the change of NT-proBNP (r = –0.27, p < 0.05). In the multiple regression model, the change of both peptides during HD was significantly influenced by membrane type (p = 0.003 for BNP and p = 0.001 for NT-proBNP). NT-proBNP change during HD was further significantly influenced by LVEF (p = 0.012), sex (p = 0.002) and duration on HD (p = 0.006). Conclusions: Both BNP and NT-proBNP levels were significantly increased in HD patients prior to dialysis. The change in concentrations of both peptides during HD is influenced by membrane type. HD probably triggers increased production of both peptides and this increase is emphasized by impaired LVEF. This fact can be clinically observed only on NT-proBNP levels, because BNP levels are biased by significant removal of this protein during HD.
Effects of Indoxylsulfate on the in vitro Hepatic Metabolism of Various Compounds Using Human Liver Microsomes and Hepatocytes
Authors: Hanada Kazuhiko , Ogawa Rie , Son Kishin , Sasaki Yuuki , Kikkawa Akashi , Ichihara Shiho , Ogata Hiroyasu
Published: May 2006

Background: Alterations of hepatic drug metabolism in patients with renal failure are poorly understood. In this study, the effects of uremic substances that can be removed by hemodialysis on in vitrohepatic drug metabolism were studied using human liver microsomes and hepatocytes. Methods: The metabolism of various compounds that undergo oxidation and glucuronidation in the liver was studied using human liver microsomes and hepatocytes in the presence of 11 uremic substances removable by hemodialysis. Results: The formation of resorufin from ethoxyresorufin was inhibited by 3-indoxylsulfate and 3-indoleacetic acid. The formation of 6β-hydroxytestosterone from testosterone was inhibited only by 3-indoxylsulfate. These uremic substances reduced the maximum metabolic rate but not the affinity, suggesting that the inhibitory mechanism was noncompetitive. The inhibition of formation of resorufin and 6β-hydroxytestosterone by 3-indoxylsulfate was also observed in human hepatocytes. The elimination of nicardipine in liver microsomes was decreased significantly in the presence of 3-indoxylsulfate and 3-indoleacetic acid. Conclusion: The hepatic metabolism of certain drugs may be inhibited directly by uremic substances such as 3-indoxylsulfate that accumulate in the plasma in patients with chronic renal failure.
Mid-Term Efficacy of Beraprost, an Oral Prostacyclin Analog, in the Treatment of Distal CTEPH: A Case Control Study
Authors: Vizza Carmine Dario , Badagliacca Roberto , Sciomer Susanna , Poscia Roberto , Battagliese Alessandro , Schina Mauro , Agati Luciano , Fedele Francesco
Published: May 2006

Background: Prostanoids are a well-established therapy for pulmonary arterial hypertension (PAH), and observational studies suggest their efficacy even in chronic thromboembolic pulmonary hypertension (CTEPH) patients. Objective: To compare the effects of 6 months of treatment with beraprost, an orally-active prostacyclin analog, in patients with distal CTEPH and PAH. Design: Case-control study. Population: Sixteen patients with severe pulmonary hypertension (NYHA II–IV), eight with distal CTEPH matched with eight patients with idiopathic PAH for similar effort tolerance. Methods: All patients were in stable clinical and hemodynamic condition for 3 months with maximal standard therapy. During the titration phase (4 weeks) beraprost was increased to maximal tolerated dose (mean daily dosage: CTEPH 275 ± 47 µg, PAH 277 ± 47 µg) in adjunction of standard therapy, patients were followed-up for 6 months. Main Outcome Measures: World Heart Organization (WHO) functional class, exercise capacity measured by distance walked in 6 min, and systolic pulmonary pressure (echocardiography), were evaluated at baseline, and at 1-, 3- and 6-month interval. Results: At 6 months WHO class decreased significantly in both groups (CTEPH from 2.7 ± 0.6 to 2.0 ± 0.24, p < 0.05; PAH from 3.0 ± 0.26 to 2.1 ± 0.25, p < 0.05), similarly the 6-min walk distance increased significantly from baseline (CTEPH from 312 ± 31 to 373 ± 29 m, p < 0.003; PAH from 303 ± 31 to 347 ± 29, p < 0.0003). Systolic pulmonary artery pressure showed a trend toward lower value (CTEPH from 85 ± 7 m to 81 ± 6 mm Hg, p = NS; PAH from 89 ± 7 to 82 ± 5, p = NS). During the observation period we did not have any death. The drug was well-tolerated with minor side-effects. Conclusion: In patients with CTEPH beraprost had similar mid-term clinical and hemodynamic improvements than in patients with PAH.
Mycophenolate Mofetil Ameliorates Accelerated Progressive Nephropathy in Rat
Authors: Bloudíčková S. , Rajnoch J. , Lodererová A. , Honsová E. , Viklický O.
Published: May 2006

Background: Renal ischemia and hypertension have been suggested to be involved in the progression of renal diseases. Recently, we developed a model of accelerated major histocompatibility complex-independent renal injury, where high-renin hypertension aggravates functional and morphological changes induced by ischemia/reperfusion (I/R). In this model, we evaluated the effect of immunosuppressant mycophenolate mofetil (MMF) to test its capability to slow the progression of accelerated nephropathy. Methods: 34 anesthetized uninephrectomized hypertensive transgenic (mREN2)27 rats (TGR) received a clamp on the renal pedicle for 45 min. Animals were treated with MMF 10 mg/kg/day (n = 10), 20 mg/kg/day (n = 10) or placebo (n = 10) orally via gavage for 12 weeks. Four animals were sham operated and not treated. Proteinuria and blood pressure were evaluated throughout the experiment. At the end of the experiment, kidney function was evaluated and kidneys harvested for morphological analysis and immunohistochemistry (CD4+, CD8+ lymphocytes and specific rat monocyte/macrophage marker ED-1+ cells). Results: At week 12, both MMF-treated groups had lower proteinuria as compared to the placebo group (MMF 10: 22.4 ± 9.8, MMF 20: 20.9 ± 5.6 vs. 126.7 ± 35.8; p < 0.01; sham 28.1 ± 1.4 mg/day) and reduced glomerulosclerosis (MMF 10: 11.4 ± 7.8, MMF 20: 5.2 ± 2.7 vs. 20.9 ± 10.9; p < 0.05; sham 15.7 ± 9.2%). There were no differences in systolic blood pressure among groups. MMF-treated rats had lower CD4+ (MMF 10: 61.2 ± 46.4, MMF 20: 29.3 ± 18.2 vs. 125.3 ± 42.8; p < 0.01, sham 84.9 ± 6.1 cells/field of view) and CD8+ (MMF 10: 13.7 ± 10.2, MMF 20: 10.0 ± 8.1 vs. 37.8 ± 14.3; p < 0.01; sham: 31.8 ± 7.6 cells/field of view) lymphocytes infiltration and ED-1 macrophages infiltration (MMF 10: 5.5 ± 6.4, MMF 20: 2.5 ± 2.8 vs. 16.7 ± 4.1; p < 0.01; sham 12.2 ± 4.6 cells/field of view) than placebo-treated rats. Conclusion: Our results thus support the hypothesis about the key role of immune mechanisms in progression of chronic nephropathies.
Apolipoprotein E υ4 Allele Frequency in Vascular Dementia
Authors: Davidson Yvonne , Gibbons Linda , Purandare Nitin , Byrne Jane , Hardicre Jayne , Wren Joanne , Payton Antony , Pendleton Neil , Horan Michael , Burns Alistair , Mann David M.A.
Published: May 2006

Aim: The aim of the study was to investigate whether possession of the υ4 allelic form of the apolipoprotein E (APOE) gene increases the risk of developing vascular dementia (VaD). Methods:APOE allele and genotype frequencies were determined by PCR in 89 patients with possible and probable VaD and compared with those in 97 patients with possible and probable Alzheimer’s disease (AD) of similar age of disease onset and ethnic background, and with 766 control subjects drawn from the same geographical region. Results: The APOE υ4 allele frequency in all 97 patients with possible and probable AD was significantly higher (p < 0.001) than that in control subjects. However, the APOE υ4 allele frequency in all 89 patients with possible and probable VaD was also significantly higher (p < 0.001) than that in control subjects, but not significantly different from that in AD. The APOE υ4 allele frequency was similarly, and still significantly (p < 0.001), increased when only those patients with probable AD or probable VaD were considered. Conclusion: Possession of APOE υ4 allele increases the risk of VaD.
Effect of Cyclosporine A on Glucose Interstitial Concentration in Renal Cortex and Medulla from Rats
Authors: Navegantes Luiz Carlos Carvalho , Mendes Glória Elisa Florido , Lira Eduardo Carvalho , Kettelhut Ísis do Carmo , Baptista Maria Alice Sperto Ferreira , Burdmann Emmanuel A.
Published: May 2006

Aim: To standardize microdialysis in rat kidneys and address cyclosporine A (CsA) effects on renal cortex and medulla interstitial glucose. Methods: Munich-Wistar rats were treated with vehicle or CsA (15 mg/kg/day) for 3 weeks. Glucose was assessed by spectrophotometry in dialysate samples from cortex, medulla and arterial plasma. Plasma insulin was measured by radioimmunoassay. Renal blood flow (RBF) was measured by Doppler ultrasound. Creatinine and urea were measured by spectrophotometry. Results: CsA significantly increased the plasma levels of urea and creatinine (1.5 ± 0.20 vs. 0.73 ± 0.03 mg/dl in controls, p < 0.05). Medullary glucose in control was 44% lower than arterial glucose (56 ± 6 vs. 101 ± 8 mg/dl, p < 0.05). At the same time, CsA increased arterial (163 ± 35 vs. 101 ± 8 mg/dl in controls, p < 0.05) and medullary interstitial glucose (100 ± 18 vs. 56 ± 6 mg/dl in controls, p < 0.05), but did not affect cortical glucose (114 ± 21 vs. 90 ± 11 mg/dl in controls). These changes occurred in the presence of a decreased plasma insulin level (2.7 ± 0.2 vs. 9.3 ± 0.4 µU/ml in controls, p < 0.05). The increment in medullary glucose in CsA group occurred despite a reduction in RBF (4.6 ± 0.8 vs. 6.5 ± 1.0 ml/min/kidney in controls, p < 0.05). Conclusions: Microdialysis was an adequate tool to investigate in vivo regulation of renal glucose metabolism. Renal glucose uptake was dependent on medullary cells and CsA treatment induced diabetogenic effects on renal medulla in situ.
Phase II Trial of Docetaxel Therapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Hebbar Mohamed , Ernst Olivier , Cattan Stéphane , Dominguez Sophie , Oprea Corina , Mathurin Philippe , Triboulet Jean-Pierre , Paris Jean-Claude , Pruvot François-René
Published: May 2006

Objectives: We assessed the safety and efficacy of docetaxel, a microtubule inhibitor, in patients with advanced hepatocellular carcinoma (HCC). Methods: HCC patients that were not suitable for local therapy, but who possessed measurable disease, good performance status and adequate organ function were eligible. Docetaxel was administered every 3 weeks at a dose of 100 mg/m2 (or 75 mg/m2 if transaminase levels were between 1.5 and 3.5 times the upper normal limit). Efficacy was assessed radiologically every three cycles of chemotherapy. Results: Fifteen patients were enrolled: 11 males and 4 females; their median age was 64 years (range, 42–72 years). Nine patients had underlying cirrhosis. Four patients had been surgically treated before relapse (liver resection in 3 cases and transplantation in 1), 3 had been treated with arterial chemoembolization and 1 with arterial chemotherapy (doxorubicin). A total of 57 cycles of docetaxel were delivered (median 3, range 1–6). Significant toxicity was observed: mostly grade 3–4 neutropenia and fatigue (6 and 4 patients, respectively). Treatment had to be stopped because of toxicity in 6 patients, all having underlying cirrhosis. An important partial response was obtained in 1 patient, a result that enabled liver transplantation; this patient is still alive after 34 months. Five patients had transient stable disease. Conclusion: When used in this schedule, docetaxel does not appear to be safe and effective enough in patients with advanced HCC and cirrhosis.
Benefits of Screening in von Hippel-Lindau Disease – Comparison of Morbidity Associated with Initial Tumours in Affected Parents and Children
Authors: Priesemann M. , Davies K.M. , Perry L.A. , Drake W.M. , Chew S.L. , Monson J.P. , Savage M.O. , Johnston L.B.
Published: May 2006

Von Hippel-Lindau (VHL) is a rare autosomal dominant syndrome characterised by the association of retinal and CNS haemangioblastomas, phaeochromocytoma and renal cell carcinoma. If a child of an affected parent has inherited a VHL mutation or the parent’s mutation cannot be identified, then clinical screening is recommended. We report the clinical features in three parent-offspring pairs where the parents have presented clinically with renal cell carcinoma, phaeochromocytoma, cerebellar haemangioblastoma and retinal haemangioma, and the children have undergone pre-symptomatic screening. During the first screening a 13-year-old boy was diagnosed with bilateral phaeochromocytoma and later developed an endolymphatic sac tumour at 19 years. A right phaeochromocytoma was found in a 12-year-old girl who was screened from the age of 4 years and in a 13-year-old boy screened from 5 years of age. All children were asymptomatic at the time of diagnosis. These families demonstrate that clinical screening of children at risk of VHL can detect tumours before the first symptoms arise with a consequent reduction in morbidity. These observations strongly support the recommendation to undertake screening of the children of VHL patients.
Differential Susceptibility to Etoposide in Clones Derived from a Human Ovarian Cancer Cell Line
Authors: Balan K.V. , Sitaras N.M. , Dimas K. , Han Z. , Wyche J.H. , Pantazis P.
Published: May 2006

Objectives: To identify parameters/factors that may contribute to the differential sensitivity to etoposide in two clones isolated from the human ovarian carcinoma SKOV-3 cell line, which does not express p53 and is resistant to platinum-based regimens. Methods: Differential sensitivity of the cells to etoposide was monitored by microscopy to observe morphological changes, by flow cytometry analyses to detect cell cycle perturbations, and by molecular/biochemical assays to identify events involved in induction of apoptosis. Results: Etoposide treatment (1) induced apoptosis in one clone, ES, but not in another clone, ER, (2) had no effect on the expression of the antiapoptotic proteins Bcl-2 and Bcl-XL in both cell clones, whereas the proapoptotic proteins Bak and Bax were dramatically upregulated in ES, but not ER cells, and (3) induced more extensive processing of procaspase-8, procaspase-9, and the caspase-3-targeted substrates, topoisomerase I and PARP, in ES cells. Ectopic overexpression of Bcl-2 in ES cells failed to inhibit etoposide-induced apoptosis. Conclusions: The differential susceptibility of ES and ER cells to etoposide-induced apoptosis is associated with differences in several events rather than with a specific single genetic regulator of the apoptotic machinery. We propose that the differential response of ovarian cancer patients to etoposide treatment is associated with the number of etoposide-sensitive cells in the tumor.
Obstetric Uterine Rupture of the Unscarred Uterus: A Twenty-Year Clinical Analysis
Authors: Wang Yeou-Lih , Su Tsung-Hsien
Published: May 2006

Background:Rupture of the unscarred uterus is a rare and potentially catastrophic event. We retrospectively reviewed the records of patients with this condition to analyze their obstetric and gynecologic history and evaluate maternal and perinatal morbidity and mortality. Methods:A total of 11 cases of rupture of the unscarred gravid uterus were managed at Mackay Memorial Hospital from January 1984 to September 2003. Data extracted from the records included the use of uterine stimulants, instrumental delivery, and prior abortion by instrumentation, clinical features, treatment, and maternal and fetal morbidity and mortality. Results:The incidence of unscarred uterine rupture is 0.009% during the 20-year study period. The most common contributing factors were prior abortion by instrumentation and the use of uterotonic agents, in three cases respectively. Fetal distress occurred in six cases and postpartum hemorrhage in two. There was no maternal death, but in two cases, there was intrauterine fetal demise or perinatal death. Conclusion:Though unexpected in a woman with an unscarred uterus, rupture should be considered as a possible cause of fetal distress or unusual pain or hypotension in the mother.