Reverse engineering field-derived vertical distribution profiles to infer larval swimming behaviors.

Biophysical models are well-used tools for predicting the dispersal of marine larvae. Larval behavior has been shown to influence dispersal, but how to incorporate behavior effectively within dispersal models remains a challenge. Mechanisms of behavior are often derived from laboratory-based studies and therefore, may not reflect behavior in situ. Here, using state-of-the-art models, we explore the movements that larvae must undertake to achieve the vertical distribution patterns observed in nature. Results suggest that behaviors are not consistent with those described under the tidally synchronized vertical migration (TVM) hypothesis. Instead, we show (i) a need for swimming speed and direction to vary over the tidal cycle and (ii) that, in some instances, larval swimming cannot explain observed vertical patterns. We argue that current methods of behavioral parameterization are limited in their capacity to replicate in situ observations of vertical distribution, which may cause dispersal error to propagate over time, due to advective differences over depth and demonstrate an alternative to laboratory-based behavioral parameterization that encompasses the range of environmental cues that may be acting on planktic organisms.

One Health collaborations for zoonotic disease control in Ethiopia.

Zoonotic diseases require a One Health approach for successful control and elimination due to the nature of their transmission between animals and humans. One Health recognises that the health of humans, animals, and the environment are all interconnected. Ethiopia has committed itself to controlling five prioritised zoonotic diseases (rabies, anthrax, brucellosis, leptospirosis and echinococcosis), using a One Health approach. The National One Health Steering Committee (NOHSC) provides a framework for national stakeholders to address gaps in multisectoral communication, coordination and collaboration. In addition, the NOHSC oversees the formation of several specialised disease-focused groups, referred to as 'Technical Working Groups' (TWGs). These TWGs are responsible for developing disease prevention and control strategies, as well as implementing disease-focused public health activities and providing recommendations to the NOHSC. Ethiopia's success using the One Health approach and its efficient control of zoonotic diseases will depend on the commitment of all member Ministries to support the NOHSC and TWGs, as well as to build capacity in Ethiopia's workforce and laboratories, a task supported by its many international partners.

Les zoonoses étant par nature des maladies transmissibles entre les animaux et l'homme, l'approche Une seule santé est la seule qui permette de les contrôler efficacement en vue de les éliminer. Le concept Une seule santé repose sur la prise en compte de l'interconnexion entre la santé humaine, celle des animaux et celle de l'environnement. L'Éthiopie s'est fixé pour objectif de lutter contre cinq maladies zoonotiques classées comme prioritaires (rage, fièvre charbonneuse, brucellose, leptospirose et échinococcose) en suivant une approche Une seule santé. Le comité de pilotage national Une seule santé (NOHSC) apporte un cadre permettant aux parties prenantes du pays de résoudre les problèmes de communication, de coordination et de collaboration intersectorielles. En outre, le NOHSC supervise la création de plusieurs groupes de travail techniques dédiés à des maladies spécifiques. Ces groupes de travail sont chargés d'élaborer des stratégies de prévention et de contrôle, de mettre en oeuvre des activités de santé publique axées sur ces maladies et de formuler des recommandations à l'intention du NOHSC. La réussite des efforts déployés par l'Éthiopie pour appliquer les principes Une seule santé et l'efficacité de la lutte contre les maladies zoonotiques dépendront de l'engagement des ministères concernés à soutenir le NOHSC et les groupes de travail techniques et à renforcer les capacités des ressources humaines et des laboratoires éthiopiens, tâche qui bénéficie de l'appui de nombreux partenaires internationaux.

Toda labor eficaz de control y eliminación de las enfermedades zoonóticas, por la propia naturaleza de su transmisión entre animales y personas, pasa por abordar estas patologías desde los planteamientos de Una sola salud, noción esta que parte del reconocimiento de que salud humana, animal y ambiental están siempre interconectadas. Etiopía está embarcada en el innegociable empeño de combatir cinco enfermedades zoonóticas consideradas prioritarias (rabia, carbunco bacteridiano, brucelosis, leptospirosis y equinococosis) trabajando desde la óptica de Una sola salud. El Comité Directivo Nacional de Una sola salud proporciona a los interlocutores del país un marco de referencia que sirve para subsanar las lagunas existentes en cuanto a comunicación, coordinación y colaboración entre los diversos sectores. Ese órgano, además, supervisa la formación de varios grupos especializados y centrados en una u otra enfermedad, denominados grupos de trabajo técnicos, que tienen por cometido elaborar estrategias de prevención y control de una enfermedad concreta, llevar adelante acciones de salud pública dirigidas contra ella y formular recomendaciones para el Comité Directivo. El éxito de Etiopía a la hora de aplicar los postulados de Una sola salud y de combatir eficazmente las enfermedades zoonóticas dependerá del nivel de compromiso con que todos los ministerios copartícipes presten apoyo al Comité Directivo y los grupos de trabajo técnicos y ayuden a instaurar en el país un tejido lo bastante solvente de laboratorios y recursos humanos, empresa esta en la que Etiopía cuenta con el respaldo de sus numerosos asociados internacionales.

Implications of new legislation (US FSMA) and guidelines (EC) on the establishment of management systems for agricultural water.

This report summarizes key messages related to agricultural water quality as discussed by an ad hoc panel at the 1st International Symposium of Food Safety in Santiago, Chile. Participating representatives of the academia, industry and government of diverse geographical backgrounds and the audience discussed topics such as (1) implications of the US Food Safety Modernization Act (FSMA: www.fda.gov/Food/GuidanceRegulation/FSMA/ucm277706.htm) on the Agricultural Water Quality, (2) comparisons between MPN and CFU in analyzing water quality, (3) alternatives to fecal indicator bacteria (FIB) to be used as indicators to evaluate water quality, and (4) vegetative buffers as an alternative to reduce pathogen loads in agricultural surface waters. Panelists identified the following key messages for each topic discussed that are related to agricultural water quality: (1) the FSMA regulation and the new guidance document elaborated by the EC are highly relevant as they provide a definition of agricultural water and specific criteria for different water uses and circumstances; (2) FSMA supports modification from MPN to CFU; (3) Growers require more alternatives for treatment of agricultural water; (4) Vegetative buffers are a potential practical and feasible alternative for agriculture producers to reduce the pathogen and fecal pollution loads of in their agricultural waters.

Molecular epidemiology of Cryptosporidium spp. and Giardia spp. in mussels (Mytilus californianus) and California sea lions (Zalophus californianus) from Central California.

Cryptosporidium and Giardia are of public health importance, with recognized transmission through recreational waters. Therefore, both can contaminate marine waters and shellfish, with potential to infect marine mammals in nearshore ecosystems. A 2-year study was conducted to evaluate the presence of Cryptosporidium and Giardia in mussels located at two distinct coastal areas in California, namely, (i) land runoff plume sites and (ii) locations near sea lion haul-out sites, as well as in feces of California sea lions (CSL) (Zalophus californianus) by the use of direct fluorescent antibody (DFA) detection methods and PCR with sequence analysis. In this study, 961 individual mussel hemolymph samples, 54 aliquots of pooled mussel tissue, and 303 CSL fecal samples were screened. Giardia duodenalis assemblages B and D were detected in hemolymph from mussels collected near two land runoff plume sites (Santa Rosa Creek and Carmel River), and assemblages C and D were detected in hemolymph from mussels collected near a sea lion haul-out site (White Rock). These results suggest that mussels are being contaminated by protozoa carried in terrestrial runoff and/or shed in the feces of CSL. Furthermore, low numbers of oocysts and cysts morphologically similar to Cryptosporidium and Giardia, respectively, were detected in CSL fecal samples, suggesting that CSL could be a source and a host of protozoan parasites in coastal environments. The results of this study showed that Cryptosporidium and Giardia spp. from the feces of terrestrial animals and CSL can contaminate mussels and coastal environments.

A preliminary evaluation into the performance of posterior resin bonded cast metal restorations (adhesive onlays).

Posterior resin bonded cast metal restorations (adhesive onlays) were used in a variety of clinical scenarios including: management of tooth wear and cracked tooth, as retainers for fixed bridge work, for correction of the occlusal plane and in providing cuspal coverage following endodontic treatment. The mean length in service for the examined onlays was 42 months, with a range of 9-75 months. Two restorations in two patients failed resulting in an overall success of 94%. Patient satisfaction was high at 95%. Such restorations seem to be a viable option for managing a number of clinical scenarios.

The potential effects of polyunsaturated ω-3 fatty acids on spinal cord injury: A systematic review & meta-analysis of preclinical evidence.

Polyunsaturated fatty acids (PUFAs) have received attention for their anti-inflammatory and antioxidant properties. Preclinical studies have investigated the efficacy of PUFAs in animal models of spinal cord injury (SCI) to determine if these properties can translate to neuroprotection and locomotor recovery. Findings from such studies have been promising, suggesting PUFAs as potential treatments against the neurological dysfunction induced by SCI. This systematic review and meta-analysis sought to investigate the efficacy of PUFAs for promoting locomotor recovery in animal models of SCI. PubMed, Web of Science and Embase (Ovid) were searched for relevant papers and those that examined the restorative effects of PUFAs on locomotor recovery in preclinical SCI models were included in our analysis. A random effects meta-analysis (restricted maximum likelihood estimator) was employed. A total of 28 studies were included and the results showed the claim that PUFAs have a beneficial therapeutic effect for promoting locomotor recovery (SMD = 1.037, 95% CI = 0.809-1.2644, p = <0.001) and cell survival (SMD = 1.101, 95% CI = 0.889-1.313, p = <0.001) in animal models of SCI. No significant differences for the secondary outcomes of neuropathic pain and lesion volume. Moderate asymmetry was observed in the funnel plots for locomotor recovery, cell survival and neuropathic pain measures, suggesting publication bias. Trim-and-fill analysis estimated 13, 3, 0 and 4 missing studies for locomotor recovery, cell survival, neuropathic pain, and lesion volume, respectively. A modified CAMARADES checklist was also used to assess risk of bias, showing that the median score for all included papers was 4 out of a possible 7.

Effect of reduced exposure times on the microhardness of nanocomposites polymerized by QTH and second-generation LED curing lights.

This study investigated the effectiveness of polymerization of various curing regimes on five nanocomposite restorative materials­Z350, Grandio, Clearfil Majesty Esthetic, Ice and Tetric EvoCeram­by utilizing microhardness measurements. Five (n=5) disc-shaped specimens of each material were subjected to one of three curing regimes: curing with a halogen light for 20 seconds, curing with an LED light for 20 seconds and curing with an LED light for 10 seconds. Immediately following curing, hardness measurements were made with a Vickers indenter at five different locations on both the top and bottom surfaces of each disc. The mean for each surface was calculated. Data were analyzed using a one-way ANOVA and post-hoc Tukey HSD (α=0.05). The results demonstrated that among the Z350 composite samples, top and bottom microhardness values showed no statistical differences when cured with the halogen 20 second or LED 20 second regimes (p>0.05). Comparison of the top and bottom values of discs cured with the LED 10 second regime demonstrated significant differences (p<0.0001). Grandio samples cured with the halogen 20 second regime showed no statistical differences between top and bottom microhardness values (p>0.05); however, the bottom values of Grandio discs cured with the LED 20 second and 10 second regimes were significantly lower when compared with top surface values (p=0.001 and p<0.0001, respectively). Clearfil Majesty Esthetic, Ice and Tetric Evo Ceram samples cured with the halogen 20 second regime produced significantly lower bottom microhardness values, while both LED regimes produced top and bottom surfaces that were statistically comparable. The conclusion may be drawn that LED 10 second curing regimes were insufficient to cure Z350 and Grandio, while they were adequate for curing Clearfil Majesty Esthetic, Ice and Tetric EvoCeram.

Structural and IgE binding analyses of recombinant Der p 2 expressed from the hosts Escherichia coli and Pichia pastoris.

BACKGROUND: The house dust mite allergen Der p 2 is one of the most important indoor allergens associated with allergic disease. Recombinant Der (rDer) p 2 with high IgE binding activity can be readily produced in Escherichia coli and Pichia pastoris, but the structure and IgE binding of the different methods of preparation have not been compared. METHODS: Secondary structure was assessed by circular dichroism (CD). Intrinsic fluorescence and hydrophobic probe (1-anilinonaphthalene 8-sulphonic acid, ANS) were used to study the Der p 2 hydrophobic cavity. IgE binding was assessed by ELISA inhibition. RESULTS: CD analysis showed the expected secondary structure for both nDer p 2 and refolded Der p 2 prepared from E. coli inclusion bodies but primarily random structure for Der p 2 secreted from P. pastoris. The secreted product, however, had disulphide bonding and could be refolded to a similar structure to natural Der (nDer) p 2 after precipitation with trichloro-acetic or ammonium sulphate. ANS binding and intrinsic Trp92 fluorescence showed that all recombinant proteins were different to nDer p 2 and that the allergen secreted from P. pastoris did not form a hydrophobic cavity. Despite the marked structural changes, all preparations of Der p 2 had similar IgE binding to nDer p 2. CONCLUSION: Despite almost identical IgE binding, rDer p 2 prepared from both E. coli and P. pastoris showed structural differences to nDer p 2. Der p 2 secreted from P. pastoris lacked most of the natural structure, but refolding could induce the natural structure.

Toxoplasma gondii seroprevalence and association with equine protozoal myeloencephalitis: A case-control study of Californian horses.

While toxoplasmosis is not commonly considered a clinical disease of equines, previous seroprevalence studies have reported differing background rates of Toxoplasma gondii infection in horses globally. The objective of this study was to evaluate possible associations between T. gondii seroprevalence and clinical signs of equine protozoal myeloencephalitis (EPM) in horses. Using a case-control study design, 720 Californian horses with neurologic signs compatible with EPM were compared to healthy, non-neurologic horses for the presence of T. gondii antibodies (using indirect fluorescent antibody tests [IFAT]). Toxoplasma gondii seroprevalence among cases and controls was determined at standard serum cut-offs: 40, 80, 160, 320, and 640. At a T. gondii titre cut-off of 320, horses with clinical signs compatible with EPM had 3.55 times the odds of a seropositive test compared to those without clinical signs (P<0.01) when adjusted for covariates. When restricted to the autumn season and at the same titre cut-off, an EPM suspect horse had 6.4 times the odds of testing seropositive to T. gondii, compared to non-neurologic horses. The association between high T. gondii titres and clinical signs compatible with EPM is potentially reflective of toxoplasmosis in equines. Serologic testing of cerebrospinal fluid and isolation of T. gondii in EPM suspect cases should be considered. Future studies investigating the relationship between T. gondii and EPM are warranted.

Tooth surface loss in adult subjects attending a university dental clinic in Trinidad.

OBJECTIVES: To determine the prevalence of tooth surface loss (TSL) in a sample of subjects attending a university dental clinic in Trinidad and to investigate the relationship to tooth brushing, medical history, parafunction and dietary habits. DESIGN: Tooth surface loss was measured clinically by the index used in the 1998 UK, Adult Dental Health Survey. SETTING: Trinidad, West Indies. PARTICIPANTS: Convenience sample of adult subjects attending The University of the West Indies Dental School Polyclinic, Mount Hope. METHODS: A questionnaire was administered and tooth surface loss measured clinically. MAIN OUTCOME MEASURES: mild, moderate and severe tooth surface loss. RESULTS: 155 subjects were examined (mean age 40.6 years) of whom 72% had some degree of TSL with the majority (52%), exhibiting mild, 16% with moderate and 4% with severe TSL. There were associations found between TSL and age (OR=3.14), reflux (OR=1.37), parafunction (OR=1.06), weekly consumption of citrus fruits (OR=1.31) and soft drinks (OR=1.78), daily consumption of alcohol (OR=1.40) and a vegetarian diet (OR=2.79). CONCLUSIONS: Tooth surface loss in this Trinidadian population group appears to be common. Data supports an association between TSL and age, reflux parafunction and certain dietary patterns.

Comparison of human and southern sea otter (Enhydra lutris nereis) health risks for infection with protozoa in nearshore waters.

Cryptosporidium and Giardia spp. are waterborne, fecally-transmitted pathogens that cause economic loss due to gastroenteritis and beach closures. We applied quantitative microbial risk assessment (QMRA) to determine the health risks for humans and sea otters due to waterborne exposure of Cryptosporidium and Giardia spp. when swimming in three types of surface waters: river, stormwater and wastewater effluent during the wet and dry seasons in the central coast of California. This is the first application of QMRA to estimate both the probability of infection in Southern sea otters and the probability of illness in humans, using microbial source tracking (MST) as a variable. Children swimming close to stormwater discharges had an estimated Cryptosporidium-associated illness probability that exceeded the accepted U.S. EPA criteria (32 illnesses/1000 swimmers or 3.2%). Based on the assumption that sea otters are as susceptible as humans to Cryptosporidium infection, the infection probabilities were close to 2% and 16% when sea otters were swimming at the end of points of rivers and stormwater discharges, respectively. In the case of Giardia, infection probabilities of 11% and 23% were estimated for sea otters swimming at the end of point of wastewater discharges, assuming that sea otters are as susceptible as gerbils and humans, respectively. The results of this QMRA suggest that 1) humans and sea otters are at risk when swimming at outflow sites for rivers, stormwater and treated wastewater effluent; 2) reduced loads of viable protozoan cysts and oocysts in recreational water can lessen the probability of infection of humans and sea otters; and 3) the risk of infection of humans and sea otters can be reduced with the treatment of wastewater to decrease oocyst and cyst viability before effluent is released into the sea.

Emergency interventions for hyperkalaemia.

BACKGROUND: Hyperkalaemia occurs in outpatients and in between 1% and 10% of hospitalised patients. When severe, consequences include arrhythmia and death. OBJECTIVES: To review randomised evidence informing the emergency (i.e. acute, rather than chronic) management of hyperkalaemia SEARCH STRATEGY: We searched MEDLINE (1966-2003), EMBASE (1980-2003), The Cochrane Library (issue 4, 2003), and SciSearch using the text words hyperkal* or hyperpotass* (* indicates truncation). We also searched selected journals and abstracts of meetings. The reference lists of recent review articles, textbooks, and relevant papers were reviewed for additional potentially relevant titles. SELECTION CRITERIA: All selection was performed in duplicate. Articles were considered relevant if they were randomised, quasi-randomised or cross-over randomised studies of pharmacological or other interventions to treat non-neonatal humans with hyperkalaemia, reporting on clinically-important outcomes, or serum potassium levels within the first six hours of administration. DATA COLLECTION AND ANALYSIS: All data extraction was performed in duplicate. We extracted quality information, and details of the patient population, intervention, baseline and follow-up potassium values. We extracted information about arrhythmias, mortality and adverse effects. Where possible, meta-analysis was performed using random effects models. MAIN RESULTS: None of the studies of clinically-relevant hyperkalaemia reported mortality or cardiac arrhythmias. Reports focussed on serum potassium levels. Many studies were small, and not all intervention groups had sufficient data for meta-analysis to be performed. On the basis of small studies, inhaled beta-agonists, nebulised beta-agonists, and intravenous (IV) insulin-and-glucose were all effective, and the combination of nebulised beta agonists with IV insulin-and-glucose was more effective than either alone. Dialysis is effective. Results were equivocal for IV bicarbonate. K-absorbing resin was not effective by four hours, and longer follow up data on this intervention were not available from RCTs. AUTHORS' CONCLUSIONS: Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.

Self-reported percutaneous injuries of students and interns at the School of Dentistry in Trinidad: A follow up study of an updated sharps protocol

Objective: To report the results of a survey of all percutaneous injuries that occurred between 2009 ­ 2014 among students and interns at the dental school in Trinidad and to evaluate compliance with the protocol for the management of percutaneous injuries. Methods: Data was collected via questionnaires administered to 186 clinical students and interns in 2012 and 2014. Data were analysed using SPSS® 17.0 Statistical software. Results: A 90% response rate was obtained. Forty-eight persons (29%) reported one or more sharps injuries at the dental school. Of the 76 sharps injuries reported, 55 were percutaneous. Needle sticks and burs accounted for the majority of injuries and mostly occurred while working on patients. There were no significant relationships (p>0.05) between sex nor student year with the occurrence of injuries. 76% of the respondents described their concern for contracting blood borne injuries from sharps injuries as "high." After injury, 41% of the respondents followed the school's protocol for sharps injuries. Conclusion: The prevalence of percutaneous injuries among students and interns at the UWI dental school in Trinidad is 23% and occur most commonly while working on patients. Compliance with the protocol for percutaneous injuries needs to be improved. The protocol needs to be audited to improve efficiency and reinforced to the students, interns and clinical supervisors during their clinical years.

A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.

Lymphocyte recruitment to peripheral tissues is fundamental for immune surveillance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. To address this, we analyzed the chemokines expressed in the normal human nasal mucosa and found that CCL28 is preferentially expressed at a high level on the lumenal face of vascular endothelial cells in the mucosa. Analysis of the cognate chemokine receptors revealed that close to 50% of the CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3, whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In the circulation, CCR3(+) T cells comprised a small subset that did not express homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T cells abrogated the proliferative response of human blood CD4(+) T cells against the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities relevant for the upper airways. Together, these findings indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.

The Establishment of the Colombian Integrated Program for Antimicrobial Resistance Surveillance (COIPARS): A Pilot Project on Poultry Farms, Slaughterhouses and Retail Market.

The development of antimicrobial resistance among bacteria (AMR) is currently one of the world's most pressing public health problems. The use of antimicrobial agents in humans and animals has resulted in AMR which has narrowed the potential use of antibiotics for the treatment of infections in humans. To monitor AMR and to develop control measures, some countries, such as the USA, Canada and Denmark, have established national integrated surveillance systems (FDA, , CIPARS, 2007, DANMAP,2002). The components of these programs monitor changes in susceptibility/resistance to antimicrobial agents of selected zoonotic pathogens and commensal organisms recovered from animals, retail meats and humans. The rapid development of Colombia's animal production industry has raised food safety issues including the emergence of antibiotic resistance. The Colombian Integrated Surveillance Program for Antimicrobial Resistance (COIPARS) was established as a pilot project to monitor AMR on poultry farms, slaughter houses and retail markets.

GnRH-mediated desensitization of the pituitary gonadotrope is not calcium dependent.

In the present work we describe homologous desensitization of gonadotropin release from pituitary cells in response to short-term exposure to GnRH. Like the release process itself, desensitization requires receptor occupancy by an agonist. In contrast, however, inhibition of LH release by chelation of extracellular calcium or blockade of the calcium ion channel does not inhibit desensitization. Further, stimulation of gonadotropin release by ionophore A23187 (which mobilizes calcium without GnRH receptor occupancy) does not lead to desensitization. These findings indicate that the decrease in pituitary sensitivity to GnRH due to an initial exposure to the peptide can be uncoupled from LH release. The data provide the first evidence of a calcium-independent biological effect of the releasing hormone in cultured pituitary cells.

Microaggregation of the gonadotropin-releasing hormone-receptor: relation to gonadotrope desensitization.

Desensitization of the pituitary gonadotrope was examined using perifusion of immobilized dispersed cells. Specifically, a relatively brief (20 min) pulse of GnRH was shown to result in markedly reduced release of LH in response to subsequent administration of the releasing hormone. Derivatives of cAMP exerted neither an inhibitory nor a stimulatory effect on desensitization. Nonreceptor mediated secretagogues (phorbol dibutyrate and melittin) promoted gonadotropin release without desensitizing pituitary cells indicating that release and desensitization are dissociable. However, conditions that promote GnRH receptor-receptor cross-linking did lead to reduced GnRH-responsiveness, even when the receptor was occupied by an antagonist. Cells were perifused with a conjugate consisting of two dimers of a pure GnRH-antagonist (D-pGlu1-D-Phe2-D-Trp3-D-Lys6-GnRH) attached to cross-reacting antibody. The antagonist conjugate, now able to cross-link (microaggregate) GnRH receptors, is converted to an agonist. In the present work we show that the conjugate stimulates desensitization in addition to release of LH. This observation suggests that microaggregation is the final step common to both pathways, on the one hand leading to Ca2+ mobilization and release of LH, and on the other, leading to Ca2+ independent receptor-mediated desensitization.

Altered pituitary responsiveness to gonadotropin- releasing hormone in middle-aged rats with 4-day estrous cycles.

We employed a perifusion system to compare the GnRH responsiveness of pituitaries removed from young (3-6 months old) and middle-age (10-14 months old) female rats with 4-day estrous cycles in order to determine whether changes at this locus may contribute to alterations in LH secretion which precede a loss of regular estrous cycles. Pituitaries were removed and halved on each day of the 4-day cycle; one hemipituitary was retained for measurement (by RIA) of LH content. The second half was perifused for 2.5 h with medium 199 plus BSA, then stimulated for 6 h with 10(-7) M GnRH in medium 199 plus BSA. Results were as follows. 1) Within young and middle-aged groups, the magnitude of GnRH-stimulated LH release varied with stage of the estrous cycle (proestrus, diestrous day 2 greater than estrus, diestrous day 1). General patterns of LH release were similar between age groups; however, pituitaries removed from middle-aged females released significantly less LH on proestrus and diestrous day 1 than did those removed from young females. 2) The time required to reach maximal response to GnRH also varied with the estrous stage; response times were shortest on proestrus and estrus in both age groups. The time to maximal response was significantly longer in the middle-aged vs. the young group on all days of the estrous cycle except diestrous day 2. 3) Within age groups, pituitary LH content varied with the estrous cycle in a pattern similar to that of GnRH responsiveness. Between groups, LH content in middle-age females was equivalent to or greater than that in young females on all days of the cycle. These results indicate that reduced pituitary responsiveness to GnRH may contribute to the delayed attenuated proestrous LH surge that precedes reproductive senescence in the female rat.

Abducens nerve palsy due to spontaneous dissection of the internal carotid artery.

A patient had angiographic and computed tomographic features of a dissecting aneurysm of the extracranial internal carotid artery, with intracranial extension into the cavernous sinus. Isolated abducens nerve palsy resolved without treatment, within a two-month period.

Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study.

A randomized, double-blinded, placebo-controlled, two-year multicenter study demonstrated that natural human fibroblast interferon (interferon beta) administered intrathecally (IT) is effective in reducing the exacerbations of exacerbating-remitting multiple sclerosis (MS). The mean reduction in exacerbation rate of 34 patients with MS who received interferon beta administered IT was significantly greater during the study than that of 35 control patients who received placebo. The prestudy exacerbation rates were comparable for both patients who received interferon beta and control patients, but the exacerbation rate of patients receiving interferon beta at the end of the study was significantly lower than that of the control patients. Interferon beta was administered by nine or ten lumbar punctures for the first six months of the study, and observations were continued for two years. In 95% of the recipients, interferon beta therapy was well tolerated, and the side effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin dramatically reduced the toxicity of interferon beta therapy and played an important role in successful double blinding. This study confirms a preliminary report on 20 patients that initially suggested that interferon beta administered IT was of benefit in patients with MS. The number of treatments was fewer and the dosage of interferon beta administered was less in the present study than in the preliminary one. It is possible that even fewer treatments with lower doses of interferon beta administered might provide a similar degree of prophylaxis against exacerbations.