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OBJECTIVE: To examine the association of umbilical venous diameter and flow in monochorionic diamniotic twin pregnancy with placental sharing and fetal demise. METHODS: This was a prospective longitudinal cohort study of a consecutive series of monochorionic diamniotic twin pregnancies that underwent ultrasound assessments at 12, 16, 20 and 28 weeks' gestation. Fetal biometry (crown-rump length at 12 weeks or estimated fetal weight (EFW) thereafter) and cord insertion sites were recorded at each visit, as well as the diameter of the umbilical vein (UV) in both the intra-abdominal part and a free loop of the umbilical cord. Time-averaged maximum velocity in the intra-abdominal part of the UV was measured to calculate UV-flow. Univariate and multivariate linear regression analyses were performed to assess the relationship between intertwin ratios of these variables and placental sharing at 12, 16, 20 and 28 weeks' gestation. Placental sharing was calculated by dividing the larger by the smaller placental share, as measured on placental injection studies after birth. Additionally, the Mann-Whitney U-test and receiver-operating-characteristics-curve analysis were used to explore the relationship between the occurrence of fetal demise and intertwin differences in fetal biometry, cord insertion sites, UV diameters and flow at 12, 16, 20 and 28 weeks. RESULTS: Of 200 consecutive monochorionic twin pregnancies enrolled, injection studies were performed in 165 (82.5%) placentas. On univariate analysis, intertwin differences in fetal biometry, cord insertions and UV variables were associated significantly with placental sharing at 12, 16, 20 and 28 weeks' gestation. On multivariate analysis, intertwin differences in fetal biometry, cord insertions and all three UV variables remained associated significantly with placental sharing at 12 and 16 weeks. However, at 20 and 28 weeks, only the intertwin EFW ratio was associated consistently with placental sharing. Fetal demise of one or both twins complicated 26 (13.0%) pregnancies. Differences in EFW and cord insertion sites were not associated significantly with fetal demise, while at 16 weeks, differences in intra-abdominal UV diameter and flow were associated with an increased risk of subsequent fetal demise. CONCLUSIONS: At 12 and 16 weeks' gestation, intertwin differences in UV diameter and flow reflect placental sharing more accurately than do differences in fetal growth and cord insertion sites. At 16 weeks, discordance in intra-abdominal UV diameter and flow is also associated with an increased risk of fetal demise. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:60 issue:4 pages:514-522 ispartof: location:England status: published

Despite its assumed global nature, there are very few detailed stratigraphic records of the late Cenomanian to the early Turonian Oceanic Anoxic Event 2 from the Southern Hemisphere. A highly resolved record of environmental changes across the Cenomanian–Turonian boundary interval is presented from Ocean Drilling Program Site 1138 on the central Kerguelen Plateau (southern Indian Ocean). The new data lead to three key observations. Firstly, detailed biostratigraphy and chemostratigraphy indicate that the record of Oceanic Anoxic Event 2 is not complete, with a hiatus spanning the onset of the event. A decrease in glauconite and highly weathered clays after the onset of Oceanic Anoxic Event 2 marks the end of the hiatus interval, which can be explained by a relative sea-level rise that increased sediment accommodation space on the Kerguelen Plateau margin. This change in depositional environment controlled the timing of the delayed peak in organic-matter burial during Oceanic Anoxic Event 2 at Site 1138 compared with other Oceanic Anoxic Event 2 locations worldwide. A second key observation is the presence of cyclic fluctuations in the quantity and composition of organic matter being buried on the central Kerguelen Plateau throughout the latter stages of Oceanic Anoxic Event 2 and the early Turonian. A close correspondence between organic matter, sedimentary elemental compositions and sediments recording sea-floor oxygenation suggests that the cycles were mainly productivity-driven phenomena. Available age-control points constrain the periodicity of the coupled changes in sedimentary parameters to ca 15 to 50 ka, suggesting a link between carbon burial and astronomically forced climatic variations (precession or obliquity) in the Southern Hemisphere mid-latitudes both during, and after, Oceanic Anoxic Event 2: fluctuations that were superimposed on the impact of global-scale processes. Finally, trace-metal data from the non-sulphidic black shale unit at Site 1138 provide the first evidence from outside of the proto-North Atlantic region for a global drawdown of seawater trace-metal (Mo) inventories during Oceanic Anoxic Event 2. This article is protected by copyright. All rights reserved.

Migraine is a neurological disorder that is far more than just a bad headache. A hallmark of migraine is altered sensory perception. A likely contributor to this altered perception is the neuropeptide calcitonin gene-related peptide (CGRP). Over the past decade, CGRP has become firmly established as a key player in migraine. Although the mechanisms and sites of action by which CGRP might trigger migraine remain speculative, recent advances with mouse models provide some hints. This brief review focuses on how CGRP might act as both a central and peripheral neuromodulator to contribute to the migraine-like symptom of light aversive behaviour in mice.

Introduction: The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. Object: The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. Methods: Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol® 980) or kappa carrageenan potassium salt (Gelcarin® GP‐812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen™ TR‐1), xanthan gum or guar gum). Hydrogels were characterized by means of physico‐chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check‐all‐that‐apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. Results: Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. Conclusion: Physico‐chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin. Fil: Parente, M. E.. Universidad de la República; Uruguay Fil: Ochoa Andrade, A.. Universidad de la República; Uruguay Fil: Ares, G.. Universidad de la República; Uruguay Fil: Russo, F.. Universidad de la República; Uruguay Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Objective The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system. Methods Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human. Receptor pharmacology was quantified using sensitive signaling assays in primary rat TG neurons. Results mRNA and histological expression analysis in rat and human samples revealed the presence of two CGRP-responsive receptors (AMY1: calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the CGRP receptor (calcitonin receptor-like receptor/RAMP1). In support of this finding, quantification of agonist and antagonist potencies revealed a dual population of functional CGRP-responsive receptors in primary rat TG neurons. Interpretation The unexpected presence of a functional non-canonical CGRP receptor (AMY1) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine.

To examine calcitonin gene-related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state.The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the Calca gene that encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of CT called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine.We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro-inflammatory agents in vitro. Quantitative polymerase chain reaction and immunohistochemistry were used to evaluate changes in messenger ribonucleic acid (mRNA) and protein levels of CGRP and proCT.Whole mouse trigeminal ganglia cultured for 24 hours showed a 10-fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia, and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia.These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine.

The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty-eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3-month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1-year follow-up, BMI (P

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL) >or=3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was >or=3.0 in 97 patients (group A) and

Molecular dynamics computer simulations are used to probe the development of the surface morphology and the processes that determinethe depth resolution in depth profiling experiments performed by secondary ion and neutral mass spectrometry (SIM5/5NMS). The Ag(111) surface is irradiated by an impact of 20-keV Au 3 , C 60 and Ar 872 clusters that represent a broad range of cluster projectiles used in SIMS/SNMS experiments. Improvements in the simulation protocol including automation and optimal sample shape allow for at least 1000 consecutive impacts for each set of initial conditions. This novel approach allows to shrink the gap between single-impact simulations and real experiments in which numerous impacts are used.

ummary Background Octreotide has shown to be effective against rebleeding from gastrointestinal angiodysplasias, but a long-term daily parenteral administration is recommended. Long-acting octreotide (LAR-OCT) could overcome such a limitation, but it has not been studied extensively. Aim To investigate the usefulness of long-acting octreotide in the control of chronic bleeding from gastrointestinal angiodysplasias. Methods Thirteen patients with chronic gastrointestinal bleeding because of angiodysplasias were enrolled. Diagnosis was made by endoscopy and wireless video capsule. Long-acting octreotide was administered intramuscularly at a dosage of 10 mg/monthly for 1 year. Patients were followed up for a minimum period of 1 year, and haemoglobin levels, blood transfusions, iron supplementation and hospitalizations were recorded 1 year before and after starting long-acting octreotide therapy. Results Follow-up ranged from 12 to 60 months. Nine of 13 patients (69%) did not need blood transfusions and iron supplementation any longer; a partial improvement was observed in one patient; no effect was found in the others. No side effect was recorded in any patient. Conclusions Long-acting octreotide for 1 year may be beneficial as a rescue therapy for controlling chronic bleeding from gastrointestinal angiodysplasias in patients not eligible for surgery. Its monthly administration represents an advantage, which makes such a formulation the choice when a long-term treatment is mandatory.

Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons.

BACKGROUND: Mutations in the PITX2 homeobox gene are known to contribute to Axenfeld-Rieger syndrome (ARS), an autosomal-dominant developmental disorder. Although most mutations are in the homeodomain and result in a loss of function, there is a growing subset in the C-terminal domain that has not yet been characterized. These mutations are of particular interest because the C-terminus has both inhibitory and stimulatory activities. METHODS: In this study we used a combination of in vitro DNA binding and transfection reporter assays to investigate the fundamental issue of whether C-terminal mutations result in gain or loss of function at a cellular level. RESULTS: We report a new frameshift mutation in the PITX2 allele that predicts a truncated protein lacking most of the C-terminal domain (D122FS). This newly reported mutant and another ARS C-terminal mutant (W133Stop) both have greater binding than wild-type to the bicoid element. Of interest, the mutants yielded ! 5-fold greater activation of the prolactin promoter in CHO cells, even though the truncated proteins were expressed at lower levels than the wild-type protein. The truncated proteins also had greater than wild-type activity in 2 other cell lines, including the LS8 oral epithelial line that expresses the endogenous Pitx2 gene. CONCLUSIONS: The results indicate that the PITX2 C-terminal domain has inhibitory activity and support the notion that ARS may also be caused by gain-of-function mutations. Birth Defects Research (Part A) 76:175‐181, 2006. © 2006 Wiley-Liss, Inc.

CyclosporinA (CsA) is an immunosuppressive drug which induces severe adverse effects such as cardiotoxicity and nephrotoxicity. In several therapeutic protocols CsA is used in association with corticosteroids to obtain better therapeutic results. Recently, our studies showed that CsA increases blood pressure while inhibit Nitric Oxide (NO) production in vivo. In this study we evaluated in rat cardiomyocytes the effects of CsA, used alone or in association with Hydrocortisone (HY), on intracellular calcium concentration, NO production and lipid peroxidation (MDA level). Our results demonstrated that CsA increased intracellular calcium and such effect was dose-dependent. HY used alone, slightly decreased intracellular calcium, while dramatically reduced CsA-induced calcium fluxes. CsA (3.2 microM) increased lipid peroxidation and this effect was blunted by HY. Both CsA and HY inhibited NO production in rat cardiomyocytes acting on this pathway synergically. Our results demonstrated that in rat cardiomyocytes, CsA toxicity is due to a calcium overload, which in turn induce lipid peroxidation and determines oxidative stress-induced cell injury. Treatment with HY effectively inhibits CsA-induced toxicity, decreasing lipid peroxidation as well as calcium intracellular concentration. Our findings seem to suggest that glucocorticoids may be effective in reducing CsA-induced cardiotoxicity at concentrations which are consistent with current therapeutic doses.

Reaction energies for the degradation reactions of poly(methyl methacrylate) (PMMA) and for the cycloaddition of two ethylene molecules to form cyclobutane were calculated using the atomistic reactive empirical bond order potential ReaxFF,1 and the reaction energies were then compared to reaction energies from literature sources. The PMMA degradation reaction energies were from 7 to 25 kcal/mol less endothermic than the relevant literature values. The cycloaddition reaction energy was 5 kcal/mol less exothermic for ReaxFF compared to the literature value. Copyright © 2010 John Wiley & Sons, Ltd.

We have previously demonstrated an augmentation of serotonergic activity within various brain areas following infusion of brain-derived neurotrophic factor (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe nuclei (PAG/DR). However, the mechanism of this BDNF-induced modulatory effect on serotonergic systems was unclear. The aim of the present work was to study the regulation of tryptophan hydroxylase (TPH) mRNA levels after chronic BDNF administration in vivo. TPH mRNA levels were measured using a quantitative competitive reverse transcription polymerase chain reaction (RTPCR) assay. A significant increase in the expression of TPH mRNA (13-fold) was found within the PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained throughout the duration of infusion (11 days). This was accompanied by increased serotonin (5-hydroxytryptamine, 5-HT) levels and decreased nociceptive responsiveness assessed by tail-flick latency. BDNF induction of TPH mRNA levels was also observed in a serotonergic cell line derived from raphe neurons, indicating that BDNF can directly regulate TPH mRNA levels. These results suggest that BDNF augments 5-HT synthesis in vivo by directly enhancing steady-state TPH mRNA levels, and subsequently leading to marked behavioral alterations. J. Neurosci. Res. 52:149‐158, 1998. r 1998 Wiley-Liss, Inc.

Thyroid C cells are neural crest-derived neuroendocrine cells that can acquire features similar to serotonergic neurons. Based on developmental and phenotypic markers, we have previously proposed that C cells and serotonergic enteric neurons arise from a common sympathoadrenal progenitor. In this report, we genetically examined this relationship using mice lacking the mammalian achaete-scute homologue 1 (MASH-1) transcription factor, since MASH-1 has recently been shown to be required for differentiation of serotonergic enteric neurons. We found that MASH-1 knockout mice have a greatly reduced number of C cells based on the lack of calcitonin and serotonin immunoreactivity. In contrast, calcitonin and serotonin were still expressed in cultured mature C cells that no longer express MASH-1, demonstrating that MASH-1 is not directly required for the expression of these two markers. Hence, MASH-1 is required to establish the C-cell phenotype and supports the model that C cells lie in the neuronal differentiation pathway of the sympathoadrenal neural crest. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 126–134, 1998

Error detection and correction are essential steps in developing robust automated laboratory systems involving robots. Single-point sensors can be used to detect errors when the anticipated number is small. But the wide range of errors that can occur in an automated laboratory system makes this an impossible or impractical approach. Computer vision and image analysis techniques can be used to significantly broaden the range of dynamically identifiable error conditions. Object recognition and neural networks can be used to provide further characteristics of an identified error. By combining these techniques, it is often possible to extract sufficient information to direct a laboratory robot to clear or avoid an identified error, allowing the automated laboratory task to continue without human intervention. This has the potential to dramatically improve the overall reliability of an automated laboratory robot system. In this article, we report on the application of computer vision and neural networks to the detection of errors that can occur in a robot system designed to automate the loading and unloading of a laboratory centrifuge. © 1998 John Wiley & Sons, Inc. Lab Robotics and Automation 10: 273–282, 1998

Apert syndrome is a rare craniosynostosis syndrome with significant bilateral syndactyly of the hands and feet. Usually it is detected by ultrasonography during the third trimester unless there is a family history. We present an interesting sporadic case with features consistent with Apert syndrome detected as early as the first trimester. A first-trimester ultrasound evaluation prior to chorionic villus sampling (CVS) for maternal age 41 was within normal limits except for the suggestion of a 'mitten-like' hand and proximally placed thumb. Mid-trimester ultrasound was not diagnostic; however, following the development of polyhydramnios in the third trimester, the evaluation of the digits and facial features were strongly suggestive of Apert syndrome. Amniocentesis was performed and a molecular diagnosis of Apert syndrome was made and confirmed on cord blood.

It is well accepted that automatic garbage collection simplifies programming, promotes modularity, and reduces development effort. However it is commonly believed that these advantages do not counteract the perceived price: excessive overheads, possible long pause times while garbage collections occur, and the need to modify existing code. Even though there are publically available garbage collector implementations that can be used in existing programs, they do not guarantee short pauses, and some modification of the application using them is still required. In this paper we describe a snapshot-at-beginning concurrent garbage collector algorithm and its implementation. This algorithm guarantees short pauses, and can be easily implemented on stock UNIX-like operating systems. Our results show that our collector performs comparable to other garbage collection implementations on uniprocessor machines and outperforms similar collectors on multiprocessor machines. We also show our collector to be competitive in performance with explicit deallocation. Our collector has the added advantage of being non-intrusive. Using a dynamic linking technique and effective root set inferencing, we have been able to successfully run our collector even in commercial programs where only the binary executable and no source code is available. In this paper we describe our algorithm, its implementation, and provide both an algorithmic and a performance comparison between our collector and other similar garbage collectors. ©1997 by John Wiley & Sons, Ltd.

We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.

Photophobia is a subjective experience that alters sensory per-ception of light. Patients often describe photophobia in differentways. For example, some will say “light hurts my eyes” or “lightmakes my headache worse,” while others will not report associ-ated pain or pain aggravation, but unpleasantness, and state “Icannot stand even low levels of light.” However, regardless of thesubjective experience reported, they all manifest a very consistentbehavior; they retreat to a dark place or protect their eyes fromlight.This variability in the subjective experience of photophobicpatients is not surprising, considering that many different disor-ders can result in photophobia.We would like to put out the idea that photophobia involvesnot only pain pathways, but also limbic system pathways thatsuperimpose an emotional processing of discomfort leading tolight avoidance. The interaction of these pathways could providethe drive to seek out darkness. This is especially important in thecontext of migraine, where photophobia may reflect an allodynicresponse when even very low levels of light become painful.However, this avoidance can also be protective. Everyone expe-riences the need to avoid exposure of the eyes to high lightintensity. For example, looking directly at the sun is unpleasant,and most people will squint or look away to avoid retinaldamage. Likewise, the glare of skiing on a sunny day withoutsunglasses is unpleasant no matter how good the snow is. Wesuggest that these protective pathways are likely to be the sameones activated by low light in migraine and other pathologiesassociated with photophobia.So, how might the brain integrate light with pain and emo-tional circuits to yield the phenomena of photophobia? In thepast few years, we have begun to get glimpses of potential path-ways and the direction of needed future research. The cascadebegins with light activation of non-image-forming melanopsinretinal ganglion cells.

The lower genital tracts of 137 adolescent women were examined for the presence of Mycoplasma hominis, Ureaplasma urealyticum, and Corynebacterium genitalium in relation to sexual activity, previous pregnancy, presence of vaginal discharge and oral contraceptive use. None of the sexually inactive and 10% of the sexually active adolescent females were colonized with U. urealyticum. None of the sexually inactive and 4% of the sexually active adolescent females were colonized with C. genitalium. Nineteen percent of the sexually inactive and 36% of the sexually active adolescent females were colonized with M. hominis. The presence of M. hominis in the lower genital tract was not associated with any clinically identifiable vaginal discharge or inflammatory changes in exfoliated cervical and vaginal epithelial cells. The presence of M. hominis in the lower genital tract did not appear to be related to the use of oral contraceptives or antecedent pregnancy. There was no significant difference in the recovery rates of these microorganisms when we compared women who had non-specific vaginitis with those who did not. There is no evidence from this study that any of these microorganisms is responsible for non-specific vaginitis.

Summary: To evaluate the comparative effects of valproic acid (VPA) and valpromide (VPM) on plasma levels and protein binding of carbamazepine (CBZ) and CBZ-10,11-epoxide (CBZ-E), 12 adult epileptic patients stabilized on CBZ monotherapy were divided into two groups. One group (n = 6) received sodium valproate (1,100 mg/day) for 2 weeks, while the other group (n = 6) was given, for the same period, a dosage of VPM (1,200 mg/day) expected to produce VPA levels equivalent to those achieved with valproate. Plasma CBZ levels were not affected by either treatment. In the valproate-treated group, plasma CBZ-E levels increased by 101% (range, 29–238%) within 1 week of combined therapy (p < 0.02) and returned to baseline values after VPA treatment was stopped. In the VPM-treated patients, the elevation of plasma CBZ-E levels was much greater. In this group, plasma CBZ-E increased by 330% (range, 110–864%), and this was associated in two patients with the appearance of adverse effects which subsided after reducing the VPM dosage. The plasma protein binding of CBZ and CBZ-E was not affected significantly by VPM or valproate therapy. Plasma VPA levels were similar in the two groups. It is concluded that VPM is not simply a pro-drug of VPA. Although both VPA and VPM increase CBZ-E levels—probably by inhibiting the enzyme epoxide hydrolase—the interaction caused by VPM is of much greater magnitude and potential clinical significance. RESUME Pour evaluer les effets comparatifs de l'acide valproique (VPA) et du valpromide (VPM) sur les niveaux plasmatiques et la liaison proteique de la carbamazepine (CBZ) et de l'epoxide (CBZ-E), 12 patients epileptiques adultes stabilises en monotherapie par la CBZ ont ete divises en deux groupes. Le Premier groupe (n = 6) a recu du valproate de soude (1,100 mg/j) pendant 2 semaines alors que l'autre groupe (n = 6), pendant la měme periode, recevait du VPM (1,200 mg/j), les taux attendus de VPA devant ětre equivalents a ceux obtenus avec le valproate. Les taux plasmatiques de CBZ n'ont ete modifies par aucun des deux medicaments. Dans le groupe traite par valproate, les taux de CBZ-E ont augmente de 101% (extrěmes: 29–238%) en une semaine de traitement associe (p < 0.02) et ont retrove leur valeur initiale apres arrět du VPA, Chez les malades traites par VPM l'elevation des taux de CBZ-E etait beaucoup plus importante, de 330% (extrěmes: 110–864%). Chez 2 patients cette elevation s'est accompagnee de l'apparition d'effets secondaires qui ont diminue apres la reduction de la dose de VPM. Les liaisons proteiques de la CBZ et du CBZ-E n'ont ete affectees ni par le VPM ni par le valproate. Les niveaux plasmatiques de VPA etaient similaires dans les deux groupes. On en conclut que le VPM n'est pas simplement une pro-drogue du VPA. Bien que les deux produits fassent augmenter le niveau plasmatique du CBZ-E, probablement par inhibition de l'hydrolase de l'epoxide, l'interaction produite par le VPM est beaucoup plus importante et peut avoir une signification clinique. ZUSAMMENFASSUNG Um die Wirkungen von Valproinsaure (VPA) und Valpromid (VPM) auf die Plasmaspiegel und die Eiweisbindung des Carba-mazepin (CBZ) und von Carbamazepin-10, 11-Epoxyd (CBZ-E) vergleichen zu konnen, wurden 12 erwachsene epileptische Patienten unter CBZ-Monotherapie 2 Gruppen zugeteilt. Eine Gruppe (n = 6) erhielt 2 Wochen lang Natrium-valproat (1,100 mg/Tag), wahrend der anderen Gruppe (n = 6) wahrend der selben Zeit VPM (1,200 mg/Tag) gegeben wurde, von dem man erwartete, das es VPA-Spiegel hervorrufen wurde die denen entsprechen, die durch Valproat erreicht wurden. Die Plasma-CBZ-Spiegel wurden durch keine Behandlung verandert. In der Valproat behandelten Gruppe stiegen die Plasma CBZ-E Spiegel auf 101% (29 bis 238%) innerhalb einer Woche kombinierter Therapie (p < 0.02) und kehrten zu Ausgangswerten nach Ab-setzen von VPA zuruck. Bei VPM-behandelten Patienten war die Erhohung des Plasma-CBZ-E Spiegels viel groser. In dieser Gruppe trat das Plasma CBZ-E auf 330% erhoht (110 bis 864%) auf; dieses wurde bei 2 Patienten von unerwunschten Nebenwirkungen begleitet, die nach Reduktion von VPM verschwanden. Die Plasma-Proteinbindung des CBZ und CBZ-E wurde weder durch VPA noch durch Valproat-Therapie signifikant beein-flusst. Die Plasma-VPA-Spiegel waren in beiden Gruppen ahnlich. Es wird gefolgert, das VPM nicht nur ein Vorlaufer des VPA ist. Obwohl VPA und VPM die CBZ-E-Spiegel erhohen—wahrscheinlich durch Inhibition der Epoxydhydrolase—ist die Interaktion, die durch VPM verursacht wurde, viel groser und moglicherweise von klinischer Bedeutung.

A theoretical basis for thin-film dialysis involving binding between a ligand and nondialyzing species is presented. A general differential equation that applies to the case of equivalent, noninteracting sites is derived relating [A]F, [A]T, [P]T, and K. Numerical solutions to this equation are used to develop a series of escape curves corresponding to specific values of the parameters [P]T, [A]i, K, and k0. A general method for determining an equilibrium binding constant from thin-film dialysis data is given. A comparison of thin-film dialysis results predicted by this theory with literature data shows essential agreement.

1 Anti-inflammatory steroids reduce prostaglandin E2 (PGE2) synthesis in rat renomedullary interstitial cells in culture by inhibiting the release of arachidonic acid from membranous phospholipid stores, exhibiting antiphospholipase-like properties. 2 After treatment of the cells with dexamethasone 10(-6)M, these cells release a protein in the supernatant. 3 This supernatant is able to inhibit PGE2 secretion in untreated cells and to inhibit phospholipase A2 activity in an in vitro system. 4 Using chromatofocusing separation, we showed that two distinct proteins exist with isoelectric points of 5.8 and 8.3. 5 Using gel permeation separation, we showed that two proteins exist with apparent molecular weights of 15,000 and 30,000 daltons. 6 We conclude that, in renal cells in culture, anti-inflammatory steroids induce the synthesis and the release of two polypeptides which we have named 'Renocortins' (induced by corticoids in renal cells) causing the antiphospholipase-like action of glucocorticoids. 7 Our results are in good agreement with others, but as renal cells are not directly involved in the inflammatory process, we suggest that this steroid-induced phenomenon is not solely involved in the inflammatory reaction but is of more general physiological relevance.