bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-A and -B receptors, superoxide, and Ca2+signaling in afferent arterioles
Authors: Fellner Susan K. , Arendshorst William
Published: June 2006

It is unknown if endothelin-A and -B receptors (ETAR and ETBR) activate the production of superoxide via NAD(P)H oxidase and subsequently stimulate the formation of cyclic adenine diphosphate ribose (cADPR) in afferent arterioles. Vessels were isolated from rat kidney and loaded with fura 2. Endothelin-1 (ET-1) rapidly increased cytosolic Ca2+concentration ([Ca2+]i) by 303 nM. The superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and nicotinamide, an inhibitor of ADPR cyclase, diminished the response by ∼60%. The ETBR agonist sarafotoxin 6c (S6c) increased peak [Ca2+]iby 117 nM. Subsequent addition of ET-1 in the continued presence of S6c caused an additional [Ca2+]ipeak of 225 nM. Neither nicotinamide or 8-bromo- (8-Br) cADPR nor apocynin decreased the [Ca2+]iresponse to S6c, but inhibited the subsequent [Ca2+]iresponse to ET-1. The ETBR blockers BQ-788 and A-192621 prevented the S6c [Ca2+]ipeak and reduced the ET-1 response by more than one-half, suggesting an ETBR/ETAR interaction. In contrast, the ETAR blocker BQ-123 had no effect on the S6c [Ca2+]ipeak and obliterated the subsequent ET-1 response. ET-1 immediately stimulated superoxide formation (measured with TEMPO-9-AC, 68 arbitrary units) that was inhibited 95% by apocynin or diphenyl iodonium. S6c or IRL-1620 increased superoxide by 8% of that caused by subsequent ET-1 addition. We conclude that ETAR activation of afferent arterioles increases the formation of superoxide that accounts for ∼60% of subsequent Ca2+signaling. ETBR activation appears to result in only minor increases in superoxide production. Nicotinamide and 8-Br-cADPR results suggest that ET-1 (and primarily ETAR) causes the activation of vascular smooth muscle cell-ADPR cyclase.
Renal cortical regulation of COX-1 and functionally related products in early renovascular hypertension (rat)
Authors: Theilig F. , Debiec H. , Nafz B. , Ronco P. , Nüsing R. , Seyberth H. W. , Pavenstädt H. , Bouby N. , Bachmann S.
Published: June 2006

Renal volume regulation is modulated by the action of cyclooxygenases (COX) and the resulting generation of prostanoids. Epithelial expression of COX isoforms in the cortex directs COX-1 to the distal convolutions and cortical collecting duct, and COX-2 to the thick ascending limb. Partly colocalized are prostaglandin E synthase (PGES), the downstream enzyme for renal prostaglandin E2(PGE2) generation, and the EP receptors type 1 and 3. COX-1 and related components were studied in two kidney-one clip (2K1C) Goldblatt hypertensive rats with combined chronic ANG II or bradykinin B2receptor blockade using candesartan (cand) or the B2antagonist Hoechst 140 (Hoe). Rats (untreated sham, 2K1C, sham + cand, 2K1C + cand, sham + Hoe, 2K1C + Hoe) were treated to map expression of parameters controlling PGE2synthesis. In 2K1C, cortical COX isoforms did not change uniformly. COX-2 changed in parallel with NO synthase 1 (NOS1) expression with a raise in the clipped, but a decrease in the nonclipped side. By contrast, COX-1 and PGES were uniformly downregulated in both kidneys, along with reduced urinary PGE2levels, and showed no clear relations with the NO status. ANG II receptor blockade confirmed negative regulation of COX-2 by ANG II but blunted the decrease in COX-1 selectively in nonclipped kidneys. B2receptor blockade reduced COX-2 induction in 2K1C but had no clear effect on COX-1. We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct.
Mre11-Rad50-Nbs1 complex is activated by hypertonicity
Authors: Sheen Mee Rie , Kim Seung Whan , Jung Ju-Young , Ahn Joon Young , Rhee Juong G. , Kwon H. Moo , Woo Seung Kyoon
Published: June 2006

When exposed to hypertonic conditions, cells accumulate double-strand DNA breaks (DSBs) like they are exposed to ionizing radiation. It has been proposed that inactivation of the Mre11-Rad50-Nbs1 (MRN) complex due to nuclear exit is responsible for the accumulation of DSBs as cells fail to repair DSBs produced during normal cellular activity. In this study, we examined the MRN complex in cells switched to hypertonicity. Surprisingly, we found that the MRN complex stayed in the nucleus and remained intact in response to hypertonicity. In fact, the MRN complex was dramatically activated after 4 h of switch to hypertonicity in a dose-dependent manner as shown by formation of foci. Activation of ATM and the MRN complex by hypertonicity and bleomycin was additive as was activation of their downstream targets including γH2AX and Chk2 indicating that the cellular response to DSB was intact in hypertonic conditions. Activation of Chk2 in response to hypertonicity was not observed in mutant cells with functionally impaired MRN complex confirming that they are in the same pathway. After 20 h of a switch to hypertonicity, MRN foci and γH2AX returned to a control level, suggesting that cells adapted to hypertonicity by repairing DNA. We conclude that cells respond normally to DSB and repair the DNA damages induced by hypertonicity.
Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension
Authors: Klein Janet D. , Murrell Brian P. , Tucker Suzanne , Kim Young-Hee , Sands Jeff M.
Published: June 2006

The kidney responds to high levels of ANG II, as may occur during malignant hypertension, by increasing sodium and water excretion. To study whether kidney medullary transporters contribute to this response, rats were made hypertensive using ANG II. Within 3 days of being given ANG II, systolic blood pressure (BP) was increased (200 mmHg), vs control (130 mmHg), and remained high through day 14. Kidney inner medullary (IM) tip and base and outer medulla were analyzed for transporter protein abundance. There were significant decreases in UT-A1 urea transporter, aquaporin-2 (AQP2) water channel, and NKCC2/BSC1 Na+-K+-2Cl−cotransporter. To determine whether the decreases were a response to hypertension, ANG II, or an ANG II-induced increase in aldosterone, rats were given 1) norepinephrine (to increase BP) and 2) ANG II plus spironolactone (to block the mineralocorticoid receptor). Norepinephrine (7 days) increased BP, urine volume, sodium excretion, and decreased urine osmolality and UT-A1, AQP2, and NKCC2/BSC1 abundances, similar to ANG II. ANG II alone or with spironolactone yielded similar increases in BP, urine volume, and urine osmolality, and decreases in UT-A1 and AQP2 proteins in the IM tip. Plasma vasopressin was unaffected by treatment. Water diuresis did not change UT-A1 but decreased AQP2 and NKCC2/BSC1 abundances. We conclude that decreases in UT-A1, AQP2, and NKCC2/BSC1 proteins may contribute to the diuresis and natriuresis that occur following ANG II or norepinephrine-induced acute hypertension and do not appear to involve ANG II stimulation of aldosterone or thirst.
Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF
Authors: Burt Laura E. , Forbes Michael S. , Thornhill Barbara A. , Kiley Susan C. , Minor Jordan J. , Chevalier Robert L.
Published: June 2006

Chronic unilateral ureteral obstruction (UUO) in the neonatal rat causes delayed renal maturation, tubular apoptosis, and interstitial inflammation. Vascular endothelial growth factor (VEGF) acts as a survival factor for tubular cells and reduces renal injury in several models of renal disease. To determine whether exogenous VEGF attenuates renal injury from UUO, rats were subjected within the first 48 h of life to sham operation, partial UUO, or complete UUO. Saline vehicle or VEGF121(50 mg/kg) was injected twice daily for 7 days, after which kidneys were harvested for histological study. The density of peritubular capillaries was measured with platelet-endothelial cell adhesion molecule-1 immunostaining, proliferating nuclei were detected by proliferating-cell nuclear antigen staining, apoptosis by the transferase-mediated dUTP nick end-labeling technique, macrophages by ED-1 immunostaining, and collagen by Sirius red staining. Glomerular number and maturation index were also determined in each group. Following chronic complete UUO in the neonatal rat, peritubular capillary density was significantly decreased. Cortical capillary density was further reduced by exogenous VEGF in the partially obstructed kidney. While UUO also decreased glomerular number and delayed glomerular maturation, exogenous VEGF exerted no additional effects. Cellular proliferation and tubular apoptosis increased in proportion to the severity of obstruction, but exogenous VEGF had no additional effects on proliferation, tubular apoptosis, or macrophage infiltration. However, VEGF reduced interstitial apoptosis in the kidney with partial UUO. We conclude that VEGF does not have salutary effects on the renal lesions caused by chronic UUO in the neonatal rat and may actually worsen obstructive nephropathy by aggravating the interstitial lesions.
Expression and distribution of HuR during ATP depletion and recovery in proximal tubule cells
Authors: Jeyaraj Selvi C. , Dakhlallah Duaa , Hill Stephanie R. , Lee Beth S.
Published: June 2006

Human antigen R (HuR) is a nucleocytoplasmic shuttling protein that binds to and stabilizes mRNAs containing adenine- and uridine-rich elements. Under normal growth conditions, the bulk of HuR is maintained in the nucleus, but under conditions of cell stress, HuR may become more prevalent in the cytosol, where it can stabilize mRNA and regulate gene expression. We have studied the behavior of HuR in LLC-PK1proximal tubule cells subjected to ATP depletion and recovery. ATP depletion resulted in detectable net movement of HuR out of the nucleus, followed by net movement of HuR back into the nucleus on reversion to normal growth medium. In addition, HuR protein levels increased during energy depletion. This increase was inhibited by cycloheximide and was independent of HuR mRNA levels, since no change was noted in the quantity of HuR transcript. In contrast, recovery in normal growth medium resulted in increased HuR mRNA, while protein levels decreased to baseline. This suggested a mechanism by which previously injured cells maintained normal levels of HuR but were primed to rapidly translate increased amounts of protein on subsequent insults. Indeed, a second round of ATP depletion resulted in heightened HuR protein translation at a rate more rapid than during the first insult. Additionally, the second insult produced increased HuR levels in the cytoplasm while still maintaining high amounts in the nucleus, indicating that nuclear export may not be required on subsequent insults. These results suggest a role for HuR in protecting kidney epithelia from injury during ischemic stress.
Intersegmental Coordination During Human Locomotion: Does Planar Covariation of Elevation Angles Reflect Central Constraints?
Authors: Hicheur Halim , Terekhov Alexander V. , Berthoz Alain
Published: June 2006

To study intersegmental coordination in humans performing different locomotor tasks (backward, normal, fast walking, and running), we analyzed the spatiotemporal patterns of both elevation and joint angles bilaterally in the sagittal plane. In particular, we determined the origins of the planar covariation of foot, shank, and thigh elevation angles. This planar constraint is observable in the three-dimensional space defined by these three angles and corresponds to the plane described by the three time-varying elevation angle variables over each step cycle. Previous studies showed that this relation between elevation angles constrains lower limb coordination in various experimental situations. We demonstrate here that this planar covariation mainly arises from the strong correlation between foot and shank elevation angles, with thigh angle independently contributing to the pattern of intersegmental covariation. We conclude that the planar covariation of elevation angles does not reflect central constraints, as previously suggested. An alternative approach for analyzing the patterns of coordination of both elevation and joint (hip, knee, and ankle) angles is used, based on temporal cross-correlation and phase relationships between pairs of kinematic variables. We describe the changes in the pattern of intersegmental coordination that are associated with the changes of locomotor modes and locomotor speeds. We provide some evidence for a distinct control of thigh motion and discuss the respective contributions of passive mechanical factors and of active (arising from neural control) factors to the formation and the regulation of the locomotor pattern throughout the gait cycle.
Two-Dimensional Coincidence Detection in the Vibrissa/Barrel Field
Authors: Rodgers Krista M. , Benison Alexander M. , Barth Daniel S.
Published: June 2006

Coincidence detection in visual and auditory cortex may also be critical for feature analysis in somatosensory cortex. We examined its role in the rat posteromedial barrel subfield (PMBSF) using high-resolution arrays of epipial electrodes. Five vibrissae, forming an arc, row, or diagonal, were simultaneously or asynchronously stimulated to simulate contact with a straight edge of different angles at natural whisking velocities. Results indicated supralinear responses for both slow-wave and fast oscillations (FOs, about 350 Hz) at intervibrissa delays <2 ms. FO represented the earliest and most precisely tuned response to coincident vibrissa displacement. There was little difference in the spatiotemporal pattern of slow-wave or FO responses in the row, arc, or diagonal. This equivalence of function suggests that the PMBSF may be capable of working as a two-dimensional integrative array, processing spatial features based on coincidence detection despite the direction that the vibrissae pass across an object.
Differential expression profiling of the blind subterranean mole ratSpalax ehrenbergisuperspecies: bioprospecting for hypoxia tolerance
Authors: Avivi Aaron , Brodsky Leonid , Nevo Eviatar , Band Mark R.
Published: June 2006

The blind subterranean mole rat of the Spalax ehrenbergi superspecies, living underground and exposed to fluctuating oxygen and carbon dioxide levels, is an excellent model of hypoxic tolerance. Unique structural and functional adaptations of the cardiovascular and respiratory systems allow these underground mammals to survive at severely reduced oxygen tension. Elucidation of the natural variation and evolutionary changes under hypoxia within this superspecies may have biomedical applications in ischemic syndromes and cancer. In this study, we have compared expression profiles of muscle tissue at normoxic (21%) and hypoxic (3%) levels of oxygen concentration between two allospecies of the S. ehrenbergi superspecies exhibiting differential hypoxia tolerance in accordance with their ecological regimes. Profiling was performed by cross-species hybridization using a mouse cDNA array containing 15,000 gene elements. Results uncover species-specific responses to hypoxic stress among numerous genes involved in angiogenesis, apoptosis, and oxidative stress management. Among the most striking results are differential expressions of cardiac ankyrin repeat protein ( Carp), activating transcription factor 3 ( Atf3), LIM and cysteine-rich domains 1 ( Lmcd1), cysteine and glycine-rich protein 2 ( Csrp2), and ras homolog gene family, member B ( RhoB). These findings support the hypothesis that allospecies of the S. ehrenbergi superspecies are variably adapted to fluctuating oxygen tension. Differences may involve specific metabolic pathways and functional adaptations at the structural and molecular levels.
Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis
Authors: Li Robert W. , Meyer Matthew J. , Van Tassell Curtis. P. , Sonstegard Tad S. , Connor Erin E. , Van Amburgh Michael E. , Boisclair Yves R. , Capuco Anthony V.
Published: June 2006

Identification of estrogen-responsive genes is an essential step toward understanding mechanisms of estrogen action during mammary gland development. To identify these genes, 16 prepubertal heifers were used in a 2 × 2 factorial experiment, with ovarian status (intact or ovariectomized) as the first factor and estrogen treatment as the second (control or estradiol). Heifers were ovariectomized at ∼4.5 mo of age, and estrogen treatments were initiated 1 mo later. After 3 days of treatment, gene expression was analyzed in the parenchyma and fat pad of the bovine mammary gland using a high-density oligonucleotide microarray. Oligonucelotide probes represented 40,808 tentative consensus sequences from TIGR Bos taurus Gene Index and 4,575 singleton expressed sequence tags derived from libraries of pooled mammary gland and gut tissues. Microarray data were analyzed by use of the SAS mixed procedure, with an experiment-wide permutation-based significance level of P < 0.1. Considerable differences in basal gene expression were noted between mammary parenchyma and fat pad. A total of 124 estrogen-responsive genes were identified, with most responding only in the parenchyma or the fat pad. The majority of genes identified were not previously reported to be estrogen responsive. These undoubtedly include genes that are regulated indirectly but also include known estrogen-targeted genes and novel genes with potential estrogen-responsive elements in their promoter regions. The distinctive expression patterns regulated by estrogen in parenchyma and fat pad shed light on the need for both tissues to obtain normal mammary development.
Symptom Exacerbation and Adherence to Antiretroviral Therapy During the Menstrual Cycle: A Pilot Study
Authors: Patel Pinaki N. , Grimes Richard M.
Published: June 2006

Our objective is to investigate the relationship between drug and
menstrual cycle symptoms in HIV+ women receiving antiretroviral
therapy (HAART). Interviews were done for 12 weeks with 54 HIV+
women receiving HAART. Patients were asked if they experienced
any of 28 symptoms associated with HAART and the menstrual cycle
and about HAART adherence. Weeks were divided into menstrual weeks
(MWs), premenstrual weeks (PWs), and other weeks. Women reported
more bloating (P = .02) and cramps (P = .001) during MWs. Skin problems (P = .08) and breast tenderness (P = .03) were experienced during PWs. Feeling tired/loss of energy (P = .05), joint pain (P = .02), and chills (P = .03) were higher in non‐MW/PWs. Women were slightly less adherent during the MWs
(89%) than PWs (94%) and other weeks (93%). Feeling sad or
depressed (P = .01) was associated with nonadherence. Experiencing
certain symptoms associated with both the menstrual cycle and
HAART drugs was related with nonadherence.
Intestinal Parasitic Infections Among Pregnant Women in Venezuela
Authors: Rodríguez-Morales Alfonso J. , Barbella Rosa A. , Case Cynthia , Arria Melissa , Ravelo Marisela , Perez Henry , Urdaneta Oscar , Gervasio Gloria , Rubio Nestor , Maldonado Andrea , Aguilera Ymora , Viloria Anna , Blanco Juan J. , Colina Magdary , Hernández Elizabeth , Araujo Elianet , Cabaniel Gilberto , Benitez Jesús , Rifakis Pedro
Published: June 2006

Introduction. Intestinal parasitic infections, especially
due to helminths, increase anemia in pregnant women. The results
of this are low pregnancy weight gain and IUGR, followed by LBW,
with its associated greater risks of infection and higher
perinatal mortality rates. For these reasons, in the setting of no
large previous studies in Venezuela about this problem, a national
multicentric study was conducted. Methods. Pregnant women
from nine states were studied, a prenatal evaluation with a
coproparasitological study. Univariated and multivariated analyses
were made to determine risk factors for intestinal parasitosis
and related anemia. Results. During 19 months, 1038
pregnant women were included and evaluated. Intestinal parasitosis
was evidenced in 73.9%: A lumbricoides 57.0%,
T trichiura 36.0%, G lamblia 14.1%,
E hystolitica 12.0%, N americanus 8.1%,
E vermicularis 6.3%, S stercoralis 3.3%.
Relative risk for anemia in those women with intestinal
parasitosis was 2.56 (P < .01).
Discussion. Intestinal parasitoses could be associated
with conditions for development of anemia at pregnancy. These
features reflect the need of routine coproparasitological study
among pregnant women in rural and endemic zones for intestinal
parasites. Further therapeutic and prophylactic protocols are
needed. Additional research on pregnant intestinal parasitic
infection impact on newborn health is also considered.
Mycoplasma Genitalium Among Women With Nongonococcal, Nonchlamydial Pelvic Inflammatory Disease
Authors: Haggerty Catherine L. , Totten Patricia A. , Astete Sabina G. , Ness Roberta B.
Published: June 2006

Pelvic inflammatory disease (PID) is a frequent condition of young women, often resulting in reproductive morbidity. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are/is recovered from approximately a third to a half of women with PID, the etiologic agent is often unidentified. We need PCR to test for M genitalium among a pilot sample of 50 women with nongonococcal, nonchlamydial endometritis enrolled in the PID evaluation and clinical health (PEACH) study. All participants had pelvic pain, pelvic organ tenderness, and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Endometritis was defined as ≥5 surface epithelium neutrophils per ×400 field absent of menstrual endometrium and/or ≥2 stromal plasma cells per ×120 field. We detected M genitalium in 7 (14%) of the women tested: 6 (12%) in cervical specimens and 4 (8%) in endometrial specimens. We conclude that M genitalium is prevalent in the endometrium of women with nongonococcal, nonchlamydial PID.
Actinomyces israelii May Produce Vulvar Lesions Suspicious for Malignancy
Authors: McElroy Jennifer Y. , Gorens Marsha E. , Jackson Lisa N. , Stigger Danielle , Becker Teresa , Sheiner Eyal
Published: June 2006

Background. We present a case of Actinomyces israelii
causing vulvar mass suspicious for malignancy in a postmenopausal
woman. Case. A 60 year‐old woman presented due to a firm,
nonmobile, 10 cm vulvar mass, which had been rapidly
enlarging for 5 months. The mass was painful, with localized
pruritus and sinus tracts oozing of serosanguinous fluid. Biopsy
and cultures revealed a ruptured epidermal inclusion cyst
containing granulation tissue and Actinomyces israelii.
Conclusion. Actinomyces israelii may produce vulvar
lesions that are suspicious for malignancy. Thus, biopsies and
cultures are both mandatory while evaluating vulvar masses
suspicious for malignancy.
Endometrial Histology of Depomedroxyprogesterone Acetate Users: A Pilot Study
Authors: Thurman Andrea Ries , Soper David E.
Published: June 2006

Objective. To obtain pilot data on the endometrial histology of
Depomedroxyprogesterone acetate (Depo‐Provera, DMPA) users
experiencing breakthrough bleeding (BTB) versus users with
amenorrhea. To compare the endometrial histology of patients who
used DMPA continuously for 3–12 months versus those who used it for
13 months or more. Methods. Cross‐sectional study. Endometrial
biopsy was obtained from all consenting patients who used DMPA for at
least 3 months. Patients were divided into those with BTB in the last 3 months
versus those with amenorrhea for at least 3 months. Histology
results and duration of therapy were compared. Results. The
proportion of women with chronic endometritis, uterine polyps,
atrophic, proliferative, or progesterone‐dominant endometrium did
not differ between those DMPA users with BTB versus those with
amenorrhea. Duration of therapy did not correlate with symptoms of
BTB or endometrial histology. Chronic endometritis was the most
common histologic finding (10/40, 25%) and occurred more often
in women experiencing BTB (35% versus 15%) (RR 1.62 CI
0.91–2.87). Moreover, 45% of women with BTB had received
DMPA for more than 12 months. Conclusions. BTB was more common
than previously reported in women using DMPA for more than 12
months. Chronic endometritis, which may indicate an underlying
infectious or intracavitary anatomic etiology, has not been
previously reported as a frequent finding in DMPA users, and may
be related to ethnic or other sociodemographic characteristics of
our patient population. Further study to elucidate the etiology of
chronic endometritis in these patients is warranted.
Helicobacter pylori Seropositivity and Stool Antigen in Patients With Hyperemesis Gravidarum
Authors: Karadeniz R. Sinan , Ozdegirmenci Ozlem , Altay M. Metin , Solaroglu Ayse , Dilbaz Serdar , Hızel Nedret , Haberal Ali
Published: June 2006

The objective of this paper is to investigate whether Helicobacter
pylori is an etiologic factor in hyperemesis gravidarum. Thirty one
patients with hyperemesis gravidarum and twenty nine pregnant
controls without hyperemesis gravidarum were included in this
prospective study. All pregnant women were examined both for
Helicobacter pylori serum immunoglobulin G antibodies
(HpIgG Ab), showing chronic infection, and Helicobacter pylori
stool antigens (HpSA), showing active gastrointestinal colonization. Chi‐square
and Student t tests were used accordingly for
statistical analysis. Helicobacter pylori seropositivity
was 67.7% in the patients with hyperemesis gravidarum and
79.3% in the control group (χ2 = 1.02, P = .31). HpSA was detected in 22.6% of patients with hyperemesis gravidarum, whereas 6.9% of patients in the control group. The difference was not statistically
significant (χ2 = 2.89, P = .08). In this study, no relation was found between Helicobacter pylori and
hyperemesis gravidarum. The low social status of women in both
groups could be one of the reasons for the high prevalence of Hp
infection.
Reducing the Health Burden of HPV Infection Through Vaccination
Authors: Soper David
Published: June 2006

Human papillomavirus (HPV), a sexually transmitted infection and
the etiologic cause of genital warts and cervical cancer, is
highly prevalent in sexually active men and women. Although
cervical screening procedures have significantly reduced the
disease burden associated with HPV infection, they are expensive
and abnormal results cause significant emotional distress.
Therefore, prevention may be an effective strategy for reducing
the economic, psychosocial, and disease burden of HPV infection.
Multivalent vaccines are now in clinical development. A bivalent
vaccine that protects against HPV 16 and 18, and a quadrivalent
vaccine which protects against HPV types 6, 11, 16, and 18, have
been shown to significantly reduce the occurrence of incident and
persistent HPV infections in phase 2 clinical trials; phase 3
trials are currently underway. HPV vaccines will be most effective
when administered prior to initiation of sexual activity, and
vaccination campaigns should aggressively target preadolescent and
adolescent populations.
Comparison of Sleep Condition and Sleep-Related Psychological Activity after Cognitive-Behavior and Pharmacological Therapy for Chronic Insomnia
Authors: Wu Rengang , Bao Jinfeng , Zhang Chungai , Deng Jun , Long Chunling
Published: June 2006

Background: Previous studies of insomnia focused mainly on the improvement of sleep condition and ignored the effects of sleep-related psychological activity and daytime function after pharmacological and behavioral treatments. We compared the clinical effects of both therapies on sleep condition, sleep-related psychological activity and daytime function in chronic insomnia. Methods: Seventy-one patients with chronic insomnia were randomly divided into 4 groups and either received cognitive-behavior therapy (CBT, n = 19), pharmacological therapy (PCT, n = 17), CBT plus medication (Combined, n = 18) or placebo (n = 17). The treatments lasted for 8 weeks with follow-ups conducted at 3 and 8 months. On the day after treatment ended, all patients were assessed using a polysomnogram (PSG), a sleep diary and a psychological assessment. Results: The three active treatments were more effective than placebo at the time the treatments were completed. Subjective sleep-onset latency, sleep efficacy and total sleep time were better in the PCT group than in the CBT group. At the 3-month follow-up, subjective and objective sleep-onset latency, sleep efficacy and total sleep time were better in the CBT group than in both the PCT and the Combined group. At the 8-month follow-up, the CBT group showed a steady comfortable sleep state, while the PCT and Combined groups were gradually returning to the pre-treatment condition. The Combined group showed a variable long-term effect. On the other hand, pre-sleep arousal at nighttime, dysfunctional beliefs about sleep as well as daytime functioning in the CBT group not only improved, but was better than in the other active treatment groups. Conclusion: Medication and Combined therapy produced a short-term effect on chronic insomnia while CBT had a long-term effect of improved sleep-related psychological activity and daytime functioning.
Dose Response to Adjunctive Light Therapy in Citalopram-Treated Patients with Post-Stroke Depression
Authors: Søndergaard M.P. , Jarden J.O. , Martiny K. , Andersen G. , Bech P.
Published: June 2006

Background:Post-stroke depression affects the outcome of stroke rehabilitation and is observed in approximately 30% of all stroke patients. We investigated whether the addition of light treatment to medical antidepressants influences the course of depression as measured by the Hamilton Depression Scale. Methods: The effect of a combination of light therapy and citalopram in stroke victims receiving citalopram was examined by use of two different doses of light therapy under double-blind conditions. Altogether, 63 patients were included in the study. The mean age was 74.9 years. Results: After 4 weeks of therapy, the 6-item subscale of the Hamilton Depression Scale showed a statistically significantly larger improvement in patients receiving high-intensity light treatment compared to those treated with medium-intensity light (p < 0.05). Conclusion: This pilot study demonstrates a dose response effect of light used as an adjunct therapy to antidepressants in post-stroke patients with major depression.
Pentoxifylline Decreases Up-Regulated Nuclear Factor kappa B Activation and Cytokine Production in the Rat Retina following Transient Ischemia
Authors: Ji Qing , Zhang Lidong , Lv Ran , Jia Hongbin , Xu Jianguo
Published: June 2006

Aim: To investigate whether pentoxifylline (PTX) could influence the increased cytokine gene expression in the retina flowing transient ischemia, and if so, whether it acts through the modulation of nuclear factor kappa B (NF-ĸB) activation. Methods: Sprague-Dawley rats were randomly divided into three equal groups: control group, saline-treated group, and PTX-treated group. Increased intraocular pressure was applied for 90 min to induce retinal ischemia, and reperfusion was established by lowering the bottle to eye level. The reperfusion period lasted for 48 h. In the PTX-treated group, an initial dose of 20 mg PTX was injected via tail vein at the beginning of reperfusion. Then the rat received infusion of PTX at a rate of 6 mg/kg/h throughout the entire reperfusion period. The retinal tissues were collected at the end of 1, 6, 12, 24, and 48 h of reperfusion, respectively, for biochemical analysis. Histological examination was done on the tissues collected at the end of 48 h after reperfusion. Results: Histological examination revealed reduction of overall retinal thickness and thinning of the inner retinal layer in saline-treated rats after 48-hour reperfusion. However, PTX treatment significantly reduced the loss of overall retinal thickness and thinning of inner retinal layers. Dramatic increase in NF-ĸB activation, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production and mRNA expression were observed in the saline-treated group after reperfusion, with the peak reached around 12 h. In the PTX-treated group, NF-ĸB activation, TNF-α and IL-1β production and mRNA expression were significantly reduced at each corresponding time point compared to the saline-treated group. Conclusion: PTX decreased the up-regulated activation of NF-ĸB and the expression of proinflammatory cytokines, TNF-α and IL-1β in rat retinas following ischemia/reperfusion. This may contribute to significantly reduce the loss of overall retinal thickness and thinning of inner retinal layers.
Alkali Burns of the Eye: Effect of Immediate Copious Irrigation with Tap Water on Their Severity
Authors: Ikeda N. , Hayasaka Seiji , Hayasaka Yoriko , Watanabe Konomi
Published: June 2006

Purpose: To examine the effect of immediate irrigation on ocular alkali burn. Methods: Information on the injury, immediate irrigation, and ocular findings was retrospectively obtained from each patient’s record. Results: 36 patients (49 eyes) irrigated their eyes with tap water (the irrigation group) and 17 patients (29 eyes) did not (no irrigation group). The mean age of patients in the irrigation and no irrigation groups was 30 and 53 years, respectively. According to Hugher’s classification, 76% of eyes in the irrigation group had grade 1 injury, while 86% of eyes in the no irrigation group had grade 2 injuries. Mean time from the injury until healing was 8 days in the irrigation group and 29 days in the no irrigation group, respectively. Conclusion: Immediate copious irrigation with tap water reduced the severity in alkali burns of the eye and shortened the healing time.
The Differential Diagnosis of Red Eye: A Survey of Medical Practitioners from Eastern Europe and the Middle East
Authors: Petricek Igor , Prost Marek , Popova Anna
Published: June 2006

A survey amongst ophthalmologists and general medical practitioners from nine countries in Eastern Europe and the Middle East was conducted to estimate the percentage of patients presenting with a red eye and to examine differential diagnosis and treatment. Practitioners recorded brief details of every patient seen and detailed information concerning signs and symptoms, differential diagnosis and treatment for all patients presenting with a red eye during 20 consecutive days in the period between May and September 2004. Red eyes accounted for approximately 15% of consultations with ophthalmologists and almost 6% with general medical practitioners. Allergic conjunctivitis was the most common diagnosis (35%), followed by dry eye (25%) and bacterial conjunctivitis (24%). General medical practitioners were far more likely to prescribe a combination topical antibiotic and steroid preparation than ophthalmologists. This survey illustrates that red eye remains a very important problem for both ophthalmologists and general medical practitioners. Identification of dry eye as a common cause of red eye symptoms and more appropriate treatment of dry eye, allergic conjunctivitis and viral conjunctivitis are key messages to emerge.
Involvement of cAMP Response Element-Binding Protein Activation in Salivary Secretion
Authors: Yamada Koichi , Inoue Hiroko , Kida Satoshi , Masushige Shoichi , Nishiyama Tatsuaki , Mishima Kenji , Saito Ichiro
Published: June 2006

Objective: Saliva secretion is mediated by cAMP and the calcium signaling pathway in salivary acinar cells. The PKA signaling pathway plays an important role in protein secretion through the activation of cAMP, in fluid secretion through the elevation of intracellular calcium and in the activation of cAMP response element-binding protein (CREB), which is involved in these signaling cascades. In this study, we investigated whether the activation of CREB plays a part in the salivary secretion in mice. Methods: We examined CREB activation by assessing phosphorylation at the serine-133 position using Western blotting. Results: Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a β-adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol and isoproterenol-induced CREB phosphorylation was blocked by atropine (a muscarinic acetylcholine antagonist) and propranolol (a β-adrenergic antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol-stimulated amylase secretion from parotid acinar cells was inhibited by H89 and adenoviral dominant-negative CREB. Conclusion: These results indicate that the muscarinic and β-adrenergic activation of CREB was mediated through the PKA pathway and that CREB is involved in protein secretion from parotid acinar cells.
Significance of Akt Phosphorylation on Tumor Growth and Vascular Endothelial Growth Factor Expression in Human Gastric Carcinoma
Authors: Kobayashi Iwao , Semba Shuho , Matsuda Yoshiko , Kuroda Yoshikazu , Yokozaki Hiroshi
Published: June 2006

Objective: Hypoxia is known to be a prevalent stress stimulus and increases the transcription of vascular endothelial growth factor (VEGF) mediated by hypoxia inducible factor-1α (HIF-1α). We investigated the role of phosphatidyl inositol-3 OH kinase (PI3K)-Akt signaling in the regulation of HIF-1α and VEGF expression in human gastric adenocarcinoma. Methods: The growth-inhibitory and apoptosis-inducing effects of the LY294002 PI3K inhibitor were analyzed in four gastric cancer cell lines and in vivo. The regulatory mechanism of VEGF and HIF-1α expression under hypoxic conditions was examined in the cell cultures. In 88 gastric cancer tissue samples, phosphorylated Akt and VEGF expression were analyzed immunohistochemically. Results: LY294002 suppressed cell proliferation but induced apoptosis with decreased levels of phosphorylated Akt. HIF-1α expression and VEGF secretion were induced under hypoxic conditions and VEGF protein secretion was significantly decreased by treatment with LY294002. In tumor samples, phosphorylated Akt expression was detected in 57% of the tumors, which was correlated with high VEGF expression, angiogenesis, clinicopathological parameters as well as a poor outcome. Conclusions: These findings suggest that phosphorylated Akt (Ser473) reflects the grade of malignancy in human gastric adenocarcinomas, not only in terms of tumor growth but also with respect to tumor angiogenesis.
Impaired Endotoxin Tolerance Induction in Patients with Familial Mediterranean Fever
Authors: Davtyan Tigran K. , Hakopyan Gagik S. , Avetisyan Samvel A. , Mkrtchyan Nana R.
Published: June 2006

Objective: To investigate periodic disturbances in proinflammatory activation of neutrophils and monocytes in patients with familial Mediterranean fever (FMF) both during an attack and in remission. Methods: 20 FMF patients, who were naive to colchicine treatment and did not have amyloidosis, and 10 patients with Behçet’s disease (BD) were enrolled in this study. Phagocytosis, respiratory burst, CD11a/CD18 expression and intracellular cytokine synthesis were determined by flow cytometry. Endotoxin tolerance induction was defined by a reduced capacity of monocytes to respond to lipopolysaccharide (LPS) activation following a first exposure to LPS. Results:In FMF patients, we observed upregulation of neutrophil and monocyte phagocytic activity and oxidative burst during remission and downregulation of phagocytic activity and stimulus-dependent oxidative burst during an attack. A comparative analysis of oxidative burst has revealed that while the neutrophil population shows a certain periodicity in the increase (during remission) and decrease (during attacks) in the spontaneous and inducible respiratory burst, periodicity in the monocyte population is very poor. In addition, LPS-induced oxidative burst and CD11a/CD18 integrin surface expression is higher in patients during an attack compared to patients in remission. The induction of homologous tolerance of monocytes to the repeated action of LPS is observed in FMF patients during an attack, normal donors and patients with BD, whereas monocytes from patients in remission failed to induce LPS homologous tolerance and exhibited heightened sensitivity to bacterial endotoxin. We found that colchicine is able to restore impaired LPS homologous tolerance induction in FMF patients in remission upon increased synthesis of IL-4 in FMF patient monocytes. Conclusion: Chronic inflammation during FMF is characterized by periodic changes in monocyte and neutrophil activation and heightened sensitivity to endotoxin, which is associated with the episodic nature of FMF. Increased endotoxin sensitivity in the period of remission could result from a shift in the monocyte activation program from ‘alternatively’ into ‘classically’ activated monocytes, which may have important implications for the treatment of FMF.
How Wild-Type TP53 Is Inactivated in Undifferentiated-Type Gastric Carcinomas: Analyses of Intratumoral Heterogeneity in Deletion and Mutation of TP53
Authors: Yoshimura Akinobu , Sugihara Hiroyuki , Ling Zhi-Qiang , Peng Dun-Fa , Mukaisho Ken-ichi , Fujiyama Yoshihide , Hattori Takanori
Published: June 2006

Objective: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53 is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at advanced stages. To clarify how TP53 inactivation relates to histogenesis of UGCs, we examined p53 alterations in multiple samples of individual UGCs. Methods: We used 27 UGCs including 12 mixed types with minor tubular component (TC) and 16 with a layered structure (LS), a histological remnant of incipient signet ring cell carcinoma (SIG). We examined p53 expression immunohistochemically and analyzed loss of heterozygosity (LOH) with four microsatellite markers within 17p13.1 in multiple microdissected samples. DNA sequence of mutation hot spots in TP53 was determined in representative samples of each tumor. Results: In the mixed-type UGCs, 5 and 1 of the 8 tumors without LS showed global and regional loss of wild-type TP53, respectively, through mutation and LOH, and one fourth of the tumors with LS showed the regional loss. In the tumors with the mutation, the mutation pattern was identical between TC and poorly differentiated major component. Conclusion: The inactivation of wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC, but is less frequent and a later event in a subset of mixed-type UGC deriving from SIG.
Anaemia after Renal Transplantation – Role of Immunosuppressive Drugs and a Pathophysiological Appraisal
Authors: Goldsmith David , Al-Khoury Salam , Shah Nilesh , Covic Adrian
Published: June 2006

Improvements in patient care and longevity on dialysis programmes together with the increased numbers of patients referred for renal replacement therapy will inevitably result in enlarging numbers of subjects with functioning renal transplants. While this translates to a boon for the patients in terms of survival and quality of life, a very real problem has begun to emerge, that of post-transplantation anaemia (PTA). The prevalence of this condition has been estimated by several studies as varying somewhere between one third and two thirds of all patients, with the same attendant problems as anaemia in the context of chronic kidney disease. PTA is multifactorial in origin and involves interplay between a number of risk factors, not least of all the immunosuppressive protocol. It is the purpose of this article to briefly review the contribution from transplant immunosuppression to PTA and to assess its likely effects on and treatment options for patients.
Bartter Syndromes and Other Salt-Losing Tubulopathies
Authors: Kleta Robert , Bockenhauer Detlef
Published: June 2006

Genetic studies into rare inborn errors of renal tubular sodium handling in man have brought many interesting, sometimes surprising insights into how we can maintain our bodies’ electrolytes and fluids homeostasis. The cloning and identification of sodium transporting genes and proteins like NHE3, NKCC2, ROMK, CLCNKB, NCC, and EnaC has considerably improved our understanding of renal salt handling. Subsequently, studies of genetically engineered animals provided even more insight into the complex renal physiology. The recent discovery of the WNK kinases as regulators and integrators of specific renal transport pathways helped elucidate this further and lets us start to appreciate the full complexity of renal sodium handling. We summarize recent findings in the field in the context of human diseases and a pathophysiologic basis for their treatment.
Localization of NBC1 Variants in Rat Kidney
Authors: Endo Yoko , Yamazaki Satoru , Moriyama Nobuo , Li Yuehong , Ariizumi Takashi , Kudo Akihiko , Kawakami Hayato , Tanaka Yoshinori , Horita Shoko , Yamada Hideomi , Seki George , Fujita Toshiro
Published: June 2006

Na+-HCO3– cotransporter (NBC1) plays a major role in bicarbonate reabsorption from proximal tubules. In a previous immunohistochemical study on human kidney, we showed that the kidney-type transporter (kNBC1) was abundantly expressed in the basolateral membranes of proximal tubules while the expression of pancreatic-type transporter (pNBC1) was undetectable. In the present study we tried to determine the localization of NBC1 variants in rat kidney using the antibodies against the unique N-terminal regions of kNBC1 and pNBC1. In Western blot analysis on the membrane-enriched fraction from rat kidney both anti-kNBC1 and anti-pNBC1 antibodies yielded a ∼130 kDa band. In immunohistochemical analysis with confocal microscopy the anti-kNBC1 antibody produced a strong and exclusively basolateral labeling in proximal tubules. On the other hand, the occasional pNBC1 labeling was detected in the apical membranes of proximal tubules. The electron microscopic observation further supported the basolateral localization of kNBC1 as well as the localization of pNBC1 on the basis of the brush border. Acute metabolic acidosis did not change the protein expression levels as well as the intracellular distribution of both NBC1 variants in rat kidney. These results are consistent with a view that kNBC1 is the dominant variant that mediates bicarbonate reabsorption from rat renal proximal tubules. They also indicate that species difference may exist regarding the distribution of NBC1 variants in kidney.
The Fetal Variant of the Circle of Willis and Its Influence on the Cerebral Collateral Circulation
Authors: van Raamt A. Fleur , Mali Willem P.T.M. , van Laar Peter Jan , van der Graaf Yolanda
Published: June 2006

In a fetal-type posterior circle of Willis (FTP) there is an embryonic derivation of the posterior cerebral artery (PCA) from the internal carotid artery (ICA). Besides the fact that a larger area is thus dependent on the ICA, leptomeningeal vessels cannot develop between the anterior and posterior circulation. The tentorium namely prevents cerebellar vessels from connecting to the PCA territory. Therefore patients with an FTP could be more prone to develop vascular insufficiency. An overview of the literature is given. We propose to define a partial FTP, in which a small P1 segment between the basilar artery and the postcommunicating part of the PCA is present, and a full FTP, in which the P1 segment is absent. Whether a full FTP is a risk factor for stroke should be subject of further investigation.
Deep Vein Thrombosis following Ischemic Stroke among Asians
Authors: De Silva Deidre Anne , Pey Huey Bee , Wong Meng Cheong , Chang Hui Meng , Chen Christopher P.L.H.
Published: June 2006

Background: Deep vein thrombosis (DVT) is perceived as uncommon among Asian stroke patients. However, there is a paucity of published data, and thus, we studied the frequency, characteristics and prognosis of DVT following ischemic stroke in Asian patients with lower limb paresis. Methods: Doppler ultrasound scans of the lower limbs were performed at days 7–10 and 25–30 after stroke onset. The functional status of patients was assessed at 6 months using the modified Rankin scale. Results: DVT was detected in 30% of patients at days 7–10 and in 45% of patients at days 25–30. Most thromboses were distal. There were significant associations of age and degree of weakness with the presence of DVT at days 25–30, but not at days 7–10. DVT in the first month after stroke was associated with poorer outcome at 6 months. Conclusions: DVT following ischemic stroke among Asians is common and associated with poor functional outcome.