Management options for orbital complications of acute rhinosinusitis in pediatric patients.

OBJECTIVES: Acute bacterial rhinosinusitis (ABRS) is a common pediatric condition. Despite its tendency to heal without complications, orbital complications (OC) are seen in 6% of patients and can cause vision impairment and put life at risk. Current treatment of this complications involves systemic antibiotics with or without surgical drainage, remaining controversial the use of corticosteroids. The aim of this study is to describe our results in the management of this complication both through medical and surgical treatment, with the inclusion of corticosteroids on it. METHODS: A retrospective cross-sectional study was conducted in a tertiary hospital over pediatric patients with this complication. RESULTS: 23 patients were included with a mean age of 7.4 years. Ten of them (43.5%) presented ophthalmoplegia on admission and 2 of those also impaired visual acuity. A computerized tomography was performed in all patients and all of them received intravenous antibiotics and corticosteroids achieving that 60% did not require surgical treatment. The mean length of hospital stay was 6.2 days. CONCLUSIONS: The treatment of OC of ABRS with intravenous antibiotics and corticosteroids is safe, remaining surgical treatment available when necessary. When evolution is favorable, a reduced hospital stay must be sought.

Alterations in the non-neuronal cholinergic system induced by in-vitro exposure to diazoxon in spleen mononuclear cells of Nile tilapia (O. niloticus).

Organophosphate pesticides as diazinon disrupt the neuroimmune communication, affecting the innate and adaptive immune response of the exposed organisms. Since the target molecule of diazinon is typically the acetylcholinesterase enzyme (AChE), the existence of a non-neuronal cholinergic system in leukocytes makes them susceptible to alterations by diazinon. Therefore, the aim of this work was to evaluate the activity of AChE, acetylcholine (ACh) concentration, and the expression of nicotinic ACh receptors (nAChR) and muscarinic ACh receptors (mAChR) in spleen mononuclear cells (SMNC) of Nile tilapia (O. niloticus) exposed in vitro to diazoxon, a diazinon metabolite. SMNC were exposed in-vitro to 1 nM, 1 µM, and 10 µM diazoxon for 24 h. The enzyme activity of AChE was then evaluated by spectrophotometry, followed by ACh quantification by ultra-performance liquid chromatography. Finally, mAChR and nAChR expression was evaluated by RT-qPCR. The results indicate that AChE levels are significantly inhibited at 1 and 10 µM diazoxon, while the relative expression of (M3, M4, and M5) mAChR and (ß2) nAChR is reduced significantly as compared against SMNC not exposed to diazoxon. However, ACh levels show no significant difference with respect to the control group. The data indicate that diazoxon directly alters elements in the cholinergic system of SMNC by AChE inhibition or indirectly through the interaction with AChR, which is likely related to the immunotoxic properties of diazinon and its metabolites.

RSV infection in a macrophage-cell line activates the non-canonical NF-κB pathway and induces pro-inflammatory cytokine expression.

Respiratory syncytial virus (RSV) is a highly prevalent infectious agent that causes severe respiratory tract illnesses in infants and children worldwide. Children who have suffered severe RSV infections during infancy are prone to develop recurrent episodes of wheezing and asthma that may be associated with viral persistence. RSV infections in humans and animal models are characterized by extensive inflammatory responses. Epithelial cell lines acutely infected by RSV have shown activation of the NF-κB signaling through two independent pathways: the canonical pathway, mediated by RelA and p50 subunits, and the non-canonical pathway, mediated by the subunits RelB and p52. Herein, we investigated the state of activation of the canonical and non-canonical NF-κB signaling pathways in macrophages either acutely or persistently infected by RSV and examined the expression of pro-inflammatory mediators. Activation of NF-κB subunits was analyzed through Western blot assays using acutely RSV-infected epithelial cells as a control. The expression levels of two pro-inflammatory cytokines and a chemokine were determined by quantitative RT-PCR and through immunobead assays. The results showed that p52 was abundant during acute and persistent RSV infection, indicating that macrophages predominantly activate the non-canonical pathway. We also observed activation of IL-1ß, TNF-α and CCL5/RANTES transcription, though at higher levels in persistently infected macrophages than in acutely infected macrophages. In contrast, the protein levels of these cytokines/chemokine did not correlate with their mRNA transcription, as quantitation displayed higher levels during acute infection than in persistent infection, suggesting post-transcriptional regulation by RSV persistence.

The yin/yang of inflammatory status: Blood-brain barrier regulation during sleep.

Sleep loss induces a low-grade inflammatory status characterized by a subtle but sustained increase of pro-inflammatory mediators, which are key regulators of blood-brain barrier function. To investigate the influence of inflammatory status on blood-brain barrier dysfunction induced by sleep restriction we performed an experiment using two strains of mice with different immunological backgrounds, C57BL/6 mice that have a predominant pro-inflammatory response and BALB/c mice that have a predominant anti-inflammatory response. Mice were sleep-restricted during 10 days using the flowerpot technique during 20 h per day with 4 h of daily sleep opportunity. The systemic inflammatory status, blood-brain barrier permeability, and the hippocampal expression of neuroinflammatory markers were characterized at the 10th day. Serum levels of TNF and IFN-γ increased in sleep-restricted C57BL/6 but not in BALB/c mice; no changes in other cytokines were found. Sleep restriction increased blood-brain barrier permeability in C57BL/6 strain but not in BALB/c. The hippocampus of sleep-restricted C57BL/6 mice exhibited an increase in the expression of the neuroinflammatory markers Iba-1, A2A adenosine receptor, and MMP-9; meanwhile in sleep-restricted BALB/c mice the expression of this markers was lesser than the control group. These data suggest that cytokines may be playing a key role in modulating blood-brain barrier function during sleep restriction, and probably the effects are related to Iba-1, MMP-9 and A2A adenosine receptor overexpression.

Influencia de la vía de administración sobre el efecto del extracto etanólico de la semilla de Jatropha curcas L, en la motilidad intestinal en ratones albinos / Influence of the route of administration on the effect of ethanol extract of the Jatropha curcas L. seeds, on gut motility of albino mice

Objetivo: Determinar la influencia de la vía de administración sobre efecto de distintas dosis del extracto etanólico de la semilla de Jatropha curcas L en la motilidad intestinal de ratones. Materiales y Métodos: Se utilizaron ratones albinos machos con un peso promedio de 23 g, a los que, por vía oral e intraperitoneal, y a dosis escalonadas y no tóxicas, se les administraron extracto etanólico de la semilla de Jatropha curcas L. Los grupos experimentales fueron: suero fisiológico 0,1 mL/10 g, atropina 1 mg/Kg, extracto etanólico de semilla de Jatropha curcas L. 500, 750 y 1000 mg/Kg, respectivamente, y neostigmina 0,4 mg/Kg. Para la validación estadística se usó ANOVA con post-hoc de Sidak. Resultados: Se encontró diferencias significativas al analizar los porcentajes de motilidad intestinal de todos los grupos, sin embargo, al realizar la comparación por parejas solo se halló diferencias entre los grupos que recibieron atropina y neoestigmina (p=0,038), J. curcas L. vía oral a dosis de 500 mg/Kg y 1000 mg/Kg (p=0,001 en ambos casos). Se encontraron diferencias significativas (p>0,05) en las comparaciones entre la administración por vía oral y por vía peritoneal del extracto de J. curcas L. a dosis de 500 mg/Kg y 1000 mg/Kg. Conclusión: Se encontró influencia de la vía de administración, sobre el efecto del extracto etanólico de Jatropha curcas L. en la la motilidad intestinal en ratones albinos.

Objectives. To determine the influence of administration route of Jatropha curcas L. seeds ethanolic extract (in different doses) on intestinal motility of albino mice. Methods. Male albino mice were used with an average weight of 23 g., which the ethanolic extract of Jatropha curcas L. seeds were administered in different administration routes (oral and intraperitoneal), using staggered and non-toxic doses. The experimental groups were 0,1 mL/10 g physiological saline, atropine 1mg/Kg, neostigmine 0.4 mg/kg and Jatropha curcas L seed ethanolic extract in doses of 500, 750 and 1000mg/kg. One-way ANOVA test with Sidak post-hoc test were used to do a statistical inferences. Results. Significant differences were found when all-groups intestinal charcoal transit distance (%) were analyzed. However, when paired comparisons were made, significant differences were found between neostigmine group (p=0,038); and oral administration of J curcas L extracts in doses of 500 mg/Kg and 1000 mg/Kg (p=0.001 in both cases). Significant differences were found (p>0.05) in comparisons made between orally and intraperitoneal administration of J. curcas L. extract in doses of 500 mg/Kg and 1000 mg/Kg. Conclusion. There is some influence caused by route of administration of Jathropa curcas L. seeds ethanolic extract on intestinal motility in albino mice.

Efecto del extracto de maíz morado sobre la expresión génica de srebp-1, A5d y A6d en glándula mamaria de ratas nodrizas suplementadas con aceite de chía (Salvia Hispánica L) / Effect of purple corn extract on gene expression of srebp-1, A5d y A6d in mammary gland of nursing rats supplemented with chia oil (Salvia Hispánica L)

The effect of the dietary intake of purple-corn extract (EMM) as a source of anthocyanins and the oral supplementation of chia oil (CH), rich in α-linolenic acid on the lipid metabolism of the mammary glands were evaluated by gene expression SREBP-1, Δ6D Δ5D in 36 nursing rats distributed in olive oil (OL), chia oil (CH), olive oil - EMM (EMM OL +) or chia oil - EMM (CH + EMM) treatments. Gene expression of SREBP-1 was similar in OL and CH, increasing in presence of EMM; suggesting that under this conditions, CH and OL oils have similar effect on SREBP-1, while anthocyanins upregulate the gene expression. ALA inhibited the expression of desaturases, and the anthocyanins imaaproved Δ5D expression at control levels similar or higher in the case of Δ6D.

Se evaluó el efecto dietario de un extracto de maíz morado (EMM) como fuente de antocianinas y la suplementación oral de aceite de chía (CH), rico en ácido α-linolénico sobre la expresión génica de SREBP-1, Δ5D y Δ6D en en glándula mamaria de 36 ratas nodrizas distribuidas en cuatro tratamientos: aceites de oliva (OL), CH, OL + EMM o CH + EMM. La expresión de SREBP-1 fue similar en OL y CH, incrementándose en presencia de EMM. La expresión de Δ5D y Δ6D fue mayor en OL que en CH, donde incrementó en presencia de EMM, sugiriendo que bajo estas condiciones los aceites CH y OL tienen efectos similares sobre la expresión de SREBP-1 mientras las antocianinas regulan al alza dicha expresión. ALA inhibió la expresión de las desaturasas y la presencia de antocianinas aumentó la de Δ5D a niveles similares al control, o superiores en el caso de Δ6D.

Oxidative damage in gills and liver in Nile tilapia (Oreochromis niloticus) exposed to diazinon.

Agricultural activity demands the use of pesticides for plague control and extermination. In that matter, diazinon is one of the most widely used organophosphorus pesticides (OPs). Despite its benefits, the use of OPs in agricultural activities can also have negative effects since the excessive use of these substances can represent a major contamination problem for water bodies and organisms that inhabit them. The aim of this paper was to evaluate oxidative damage in lipids and proteins of Nile tilapia (Oreochromis niloticus) exposed acutely to diazinon (0.97, 1.95 and 3.95ppm) for 12 or 24h. The evaluation of oxidative damage was determined by quantifying lipid hydroperoxides (Fox method) and oxidized proteins (DNPH method). The data from this study suggest that diazinon induces a concentration-dependent oxidative damage in proteins, but not lipids, of the liver and gills of Nile tilapia. Furthermore, the treatment leads to a decrease in the concentration of total proteins, which can have serious consequences in cell physiology and fish development.

Whiplash-Associated Disorders : Clinical and medico-legal guidelines on the methods of ascertainment.

The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD).The document includes a detailed description of the logical and methodological steps of the ascertainment process as well as a synoptic diagram in the form of Flow Chart.

Identificación de genes clave implicados en el síndrome de Down mediante terapia génica / Identification of key genes involved in Down syndrome pathogenesis by gene therapy

La terapia génica nos ofrece la posibilidad de manipular los virus para convertir un agente infeccioso en un vehículo que transporta en su genoma secuencias de DNA con potencial terapéutico. En este trabajo hemos aprovechado la metodología que nos proporciona la terapia génica para desarrollar vectores virales derivados de virus adenoasociados y lentivirus con el objetivo de identificar genes clave (proteínas o microRNA [miRNA]) implicados en las alteraciones cognitivas presentes en el síndrome de Down (SD). Hemos demostrado que en un contexto de trisomía, como es el modelo de ratón Ts65Dn, la normalización de la expresión de Dyrk1A a través de la administración de los virus adenoasociados AAV2/1-shDyrk1A contribuye a restablecer la regulación de moléculas clave en los procesos de memoria y aprendizaje. Ello permite una atenuación de los defectos en plasticidad sináptica y facilita el desarrollo de una estrategia de aprendizaje visuoespacial más eficiente. Estos estudios refuerzan el papel destacado de Dyrk1A en los procesos cognitivos. Por otro lado, la estrategia de control de la expresión de miRNA desarrollada mediante los lentivirus Lv-anti-miR155-802 nos permite proponer a MeCP2 como un gen cuya desregulación en el síndrome de Down puede tener un papel clave en el deterioro cognitivo (AU)

Viruses have evolved ways of encapsulating and delivering their genes into human cells. Gene therapy takes advantage of this capability to manipulate the viral genome and convert an infectious agent into an efficient vector that delivers therapeutic genes. In the current work we have applied gene therapy approaches based on adeno-associated virus and lentivirus delivery to identify candidate genes (protein-coding or miRNAs) involved in the cognitive deficits in Down Syndrome. We show that the hippocampal injection of the adeno-associated virus AAV2/1-shDyrk1A normalized Dyrk1A expression in the trisomic Ts65Dn mice. As a consequence the regulation of key molecular players in memory and learning processes was rescued and mice showed an attenuation of synaptic plasticity defects and improved efficacy in learning strategies. All together these results reinforce the role of Dyrk1A in cognition. On the other hand, with the lentiviral strategydeveloped to specifically inhibit miR-155 and miR-802 (Lv-anti-miR155/802), we were able to show a tight control of the miRNAs target Mecp2 suggesting that the downregulation of MeCP2 in Down syndromecould be a contributing factor to the cognitive defects (AU)

Hemorragia digestiva alta: Helicobacter pylori e ingesta de ácido acetil salicílico / Upper gastrointetinal bleeding. Helicobacter pylori and intake of acetylsalicylic acid

Introducción. La hemorragia digestiva en niños requiere un adecuado diagnóstico etiológico, que variará en función de la localización, edad del paciente. Ante la presencia de hemorragia digestiva alta, se debe considerar la infección por Helicobacter pylori, ya que se asocia a gastritis crónica y desarrollo de úlcera garoduodenal. Además se deberán tener encuentra otros factores como realización de pruebas invasivas, ingesta de cuerpo extraño o tratamiento con antinflamatorios no esteroideos. Caso clínico. Describimos el caso de un niño de 11 años, que presenta una hemorragia digestiva alta asociada a enfermedad ulceropéptica por helicobacter pylori exacerbada por la ingesta de ácido acetil salicílico. Conclusiones. La infección por Helicobacter pylori puede permanecer asintomática hasta la edad adulta y aunque la primera manifestación suele ser el dolor abdominal, no deberemos olvidarla ante la presencia de hemorragia digestiva, patología poco habitual en la edad pediátrica, peor que se correlaciona con este microrganismo de manera similar a la población adulta. Se deberá descartar la presencia de otros factores de riesgo como la ingesta de ácido acetil salicílico u otros antinflamatorios no esteroideos, que pueden provocar exacerbaciones en una mucosa dañada previamente (AU)

Introduction. Gastrointestinal hemorrhage in children requires an adequate etiologic diagnosis, which depends on the location and the age of the patient. In upper gastrointestinal bleeding, Helicobacter pylori infection should be considered, because it is associated with chronic gastritis an peptic ulcer. In addition other factors such invasive techniques, foreign body ingestion or AINES therapy should be investigated. Clinical case. We report the case of a child under 11 years, who presents an upper gastrointestinal bleeding, associated with Helicobacter pylori peptic ulcer disease which was exacerbated by aspirin ingestion. Conclusions. Helicobacter pylori infection can remain asymptomatic until adulthood, and although the first manifestation is usually abdominal pain, we shouldn´t forget it in the presence of gastro intestinal bleeding, unusual disease in children, but with similar correlation that in the adult people. We should investigate other risk factors such as the ingestion of aspirin or other AINES, which cause exacerbation in a previously damaged mucosa (AU)

Understanding a ductal carcinoma in situ diagnosis: patient views and surgeon descriptions.

Following the release of the national clinical treatment recommendations for ductal carcinoma in situ (DCIS), consumers' and surgeons' characterisation of this disease was assessed. Telephone interviews were conducted with 231 women diagnosed with DCIS, in Victoria, Australia in 2006/2007 and 63 treating surgeons completed a mailed survey. The main outcome measures were: women's diagnostic experience, women's and surgeons' description of DCIS, women's understanding of DCIS, confusion and worry about the disease and risk perceptions. While the majority of women had not heard of DCIS prior to diagnosis, most reported a positive diagnostic experience. Surgeons' and women's description of DCIS were consistent. Women understood that DCIS is a contained disease (86%), can progress (88%) and treatment aims to prevent invasive cancer (97%). However, only 13% understood that DCIS alone cannot spread to other parts of the body. A quarter of the women were confused about the risk of DCIS spreading. Younger women had more concerns about developing breast cancer (P= 0.008) and the disease spreading (P= 0.002) and rated their risk of invasive disease higher (P= 0.007). Most women diagnosed with DCIS in 2006/2007 understand the 'early, contained nature' of the disease, but understanding of the 'non-invasive' nature of DCIS could be improved.

Therapeutic potential of cannabinoids in the treatment of neuroinflammation associated with Parkinson's disease.

The cannabinoid system is represented by two principal receptor subtypes, termed CB1 and CB2, along with several endogenous ligands. In the central nervous system it is involved in several processes. CB1 receptors are mainly expressed by neurons and their activation is primarily implicated in psychotropic and motor effects of cannabinoids. CB2 receptors are expressed by glial cells and are thought to participate in regulation of neuroimmune reactions. This review aims to highlight several reported properties of cannabinoids that could be used to inhibit the adverse neuroinflammatory processes contributing to Parkinson's disease and possibly other neurodegenerative disorders. These include anti-oxidant properties of phytocannabinoids and synthetic cannabinoids as well as hypothermic and antipyretic effects. However, cannabinoids may also trigger signaling cascades leading to impaired mitochondrial enzyme activity, reduced mitochondrial biogenesis, and increased oxidative stress, all of which could contribute to neurotoxicity. Therefore, further pharmacological studies are needed to allow rational design of new cannabinoid-based drugs lacking detrimental in vivo effects.

The impact of publication of Australian treatment recommendations for DCIS on clinical practice: A population-based, "before-after" study.

BACKGROUND: Clinical practice guidelines/recommendations have been promoted as a mechanism for ensuring evidence-based medicine. We examine the impact of the publication of Australian treatment recommendations (ATR) for ductal carcinoma in situ (DCIS) on clinical practice and surgeons' attitudes to the ATR. METHODS: All new cases of DCIS diagnosed in the 12-months immediately before the ATR release (pre-ATR: September 2002 to August 2003) and three years later (post-ATR: September 2006 to August 2007) were identified from the state of Victoria's population cancer registry. Treatment information, extracted for each case by treating surgeon or study manager, was available for 342 of 353 (97%) tumours pre-ATR and 371 of 378 (98%) tumours post-ATR. Sixty-three surgeons (58% response) completed a survey on awareness and attitudes to the ATR. RESULTS: The proportion of cases undergoing image-guided biopsy, or breast conservation surgery (BCS) did not change between surveys nor did extent of surgical margins. Compared to the pre-ATR period, more BCS cases were referred to a radiation oncologist (67% versus 58%) and more received radiotherapy (53% versus 44%) post-ATR. Tumours greater than 20 mm, of intermediate grade and moderate necrosis were more likely to receive radiotherapy post-ATR. While surgeons agreed with most recommendations, items reflecting radiotherapy recommendations generated most disagreement. CONCLUSION: With the possible exception of adjuvant radiotherapy, most DCIS cases were treated according to treatment recommendations before the ATR's release. The lack of change in radiotherapy for low grade, smaller tumours may reflect surgeon's uncertainty regarding this therapy for all BCS treated cases.

Medical attribution of common mental disorders in a rural Indian population.

Common mental disorders (CMD) refer to anxiety and depressive disorders causing significant disability and are commonly encountered in communities. Early diagnosis and treatment of these disorders can be improved if the population has a better understanding of them. This study aimed to explore the medical attribution of CMD among a rural community in South India using case vignettes. While most respondents agreed that there was a problem, they showed a preference for lay help over medical treatment. Improving awareness among rural communities of the usefulness of medical help for CMD might facilitate early diagnosis and treatment for these disorders.

Survival and degree of spread for female breast cancers in New South Wales from 1980 to 2003: implications for cancer control.

This study investigated associations of degree of spread at diagnosis of breast cancer and socio-demographic factors with the risk of death among NSW females diagnosed in 1980-2003. Trends by diagnostic period, socio-demographic differences, and the implications for cancer control were considered. NSW Central Cancer Registry data were analyzed using regression and rank-order tests to show predictors of death from breast cancer and trends in degree of spread. Compared with localized disease, case fatality was thrice and 14 times higher for cancers with regional spread and distant metastases, respectively. After adjusting for degree of spread and socio-demographic differences, the relative risk of death from breast cancer has declined in recent diagnostic periods compared with the 1980-1983 baseline, reaching a low of 0.38 (0.35, 0.40) for 1999-2003. Age-specific analyses indicated that relative risks were lower in 1999-2003 for 50-69 year olds (RR = 0.31) than younger (RR = 0.40), or older (RR = 0.46) females. Regional or distant disease at diagnosis was lowest in the older age groups, the highest socio-economic stratum and in more recent periods. Females born in non-English speaking countries presented with more advanced disease, as did metropolitan women with the highest access to health services. Degree of spread of cancer at diagnosis is a powerful predictor of case fatality. Case fatalities from breast cancer have declined by diagnostic period, after adjusting for degree of spread, which may reflect treatment and screening advances. Attention should be directed at reducing disparities by socio-economic status and encouraging migrant women to present earlier.

Prevalencia de displasia de vesícula biliar / Frequency of gallbladder dysplasia in gallbladders excised during cholecystectomy

Introducción: El cancer de vesícula biliar es una enfermedad muy frecuente en la actualidad, sobre todo en Chile, la India y Japón. La displasia de vesícula biliar es considerada como una lesión que precede la aparición de carcinoma vesicular. Objetivos: El objetivo de este estudio es determinar la prevalencia de la displasia de vesícula biliar en nuestro centro hospitalario y conocer sus características histológicas y clínicas. Material y Método: Los datos obtenidos de 1.237 informes de biopsias de colecistectomías realizadas en el hospital durante el año 2003 fueron procesados y analizados. Resultados: La prevalencia de la displasia de vesícula biliar fue de 2,5%. Del total de displasias (31 casos), 12 pertenecen a grado I (38,7%), 14 a grado II (45,16%) y 5 a grado lll-CIS ( carcinoma in situ 16%). La edad promedio en que se detectó la displasia de vesícula biliar fue de 54.7 años, siendo predominante en el sexo femenino con un 74,2%. Discusión: La displasia de vesícula biliar es una patología prevalente que sólo es posible diagnosticar mediante la histología realizada a los pacientes sometidos a colecistectomías.

Introduction: Gallbladder dysplasia is considered a premalignant stage, preceding the appearance of carcinoma. Aim: To assess the prevalence of gallbladder dysplasia in gallbladder biopsies. Material and methods: Review of pathology reports of 1237 gallbladders obtained during cholecystectomies, during 2003. Results: Thirty one reports informed the presence of dysplasia (2.5%). Of these, 12 were in stage 1 (39%), 14 were in stage 2 (45%) and 5 in stage 3-ISC (in-situ carcinoma, 16%). The mean age of patients with gallbladder dysplasia was 54 years. Discussion: Gallbladder dysplasia is common. The pathological study of the excised gallbladders is the only way to make the diagnosis.

Leptin receptor signaling and the regulation of mammalian physiology.

The adipocyte-derived hormone, leptin, signals the status of body energy stores to the central nervous system to regulate appetite and energy expenditure. A specific long-form leptin receptor (LepRb), a type I cytokine receptor, mediates leptin action on LepRb-expressing neurons in the brain. Leptin binding to LepRb activates the associated Janus kinase-2 (Jak2) tyrosine kinase to promote the phosphorylation of Jak2 and three residues on LepRb; each of these sites mediates a distinct aspect of downstream LepRb signaling, with differing physiologic functions. Tyr(1138) --> STAT3 signaling suppresses feeding, but is not required for a number of other leptin actions. Tyr(985) binds SH2-containing tyrosine phosphatase-2 and suppressor of cytokine signaling-3 and primarily mediates the attenuation of LepRb signaling in vivo. The role for Tyr(1077), the major regulator of signal transducer and activator of transcription-5 (STAT5) during leptin signaling, in the physiologic response to leptin remains unclear, although the obese phenotype of animals deleted for STAT5 in the brain suggests the potential importance of this signaling pathway. Leptin also modulates a number of other signaling pathways in the brain, including PI 3-kinase, mammalian target of rapamycin and AMP-dependent protein kinase; the pathways by which leptin controls these signals remain unclear, however, and may involve some indirect mechanisms. Important issues regarding leptin action and LepRb signaling in the future include not only the more thorough analysis of intracellular signaling pathways, but the neural substrate by which leptin acts, as most major populations of LepRb neurons remain poorly studied.

Scopolamine (hyoscine) for preventing and treating motion sickness.

BACKGROUND: Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine (hyoscine) has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness. OBJECTIVES: To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology. SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2007), MEDLINE (OVID, 1966 to May 2007), EMBASE (1974 to May 2007) CINAHL (OVID, 1982 to May 2007) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. The date of the last search was May 2007. SELECTION CRITERIA: All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered. DATA COLLECTION AND ANALYSIS: Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random-effects model. MAIN RESULTS: Of 35 studies considered potentially relevant, 14 studies enrolling 1025 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, methscopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality. Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus methscopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine. No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness. AUTHORS' CONCLUSIONS: The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, no randomised controlled trials were identified that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.

Clarifying the effects of dwarfing rootstock on vegetative and reproductive growth during tree development: a study on apple trees.

BACKGROUND AND AIMS: Despite the widespread use of dwarfing rootstocks in the fruit-tree industry, their impact on tree architectural development and possible role in the within-tree balance between growth and flowering are still poorly understood, in particular during the early years of growth. The present study addressed this question in apple trees, through a detailed analysis of shoot populations, i.e. both vegetative and flowering shoots, during tree development. METHODS: Architectural databases were constructed for trees of two cultivars that were either own-rooted or grafted on dwarfing rootstock. Within-tree shoot demographics and annual shoot characteristics, i.e. their dimensions, number of laterals and flowering, were observed from the first to the fifth year of growth and compared among scion/root system combinations. KEY RESULTS: Differences in axis demographics appeared among scion/root system combinations after the second year of growth. Differences were found (a) in the number of long axes and (b) the number of medium axes. Dwarfing rootstock reduced the total number of axes developed in a tree, and this reduction resulted from proportionally more medium axes and spurs than long axes. The life span of spurs was also shortened. These phenomena appeared after an increase in flowering that started in the second year of growth and involved both axillary and terminal positions. Flowering regularity was also increased in grafted trees. CONCLUSIONS: These results confirm that the number of long shoots and flowering potential depend on the cultivar. They indicate that tree architectural plasticity in response to its root system mainly derives from the number of medium shoots developed and follows priorities within the whole tree axis population. There was also evidence for dwarfing rootstock involvement in adjusting the flowering abundance and that differences in flowering occurrence take precedence over those regarding vegetative growth during tree development.