Gold nanoparticles (AuNP) exert immunostimulatory and protective effects in shrimp (Litopenaeus vannamei) against Vibrio parahaemolyticus.

Gold nanoparticles (AuNP) stimulate immune responses in mammals but they have not been tested in species of relevance in aquaculture. In this study the immunostimulant and protective potential of orally administered AuNP against V. parahaemolyticus, the causative agent of Acute Hepatopancreatic Necrosis Disease, was determined in shrimp. Synthetized AuNP (18.57 ±â€¯4.37 nm) were moderately dispersed with a negative ζ potential of -10.3 ±â€¯0.208 mV (pH = 7). AuNP were administered (single dose) at 0.2, 2, and 20 µg/g feed in shrimp. Hemolymph samples were withdrawn daily for 6 days. Hemolymph or hemocytes were used to determine total hemocyte counts, immune-related enzymatic activities, and expression of immune-relevant genes. Hepatopancreas was sampled for the analysis of AuNP biodistribution and histological examination. Survival was recorded daily. No mortality or toxicity signs in hepatopancreas were found. AuNP were detected in hepatopancreas. Early (24-48 h) immunostimulation was mainly related to immune gene up-regulation. Upon a challenge with V. parahaemolyticus, survival was higher (80%) and histopathological damages were lower in shrimp treated with the 2 µg/g dose when compared to the control. Therefore orally administered AuNP are proposed as immunostimulants that protect shrimp against V. parahaemolyticus infection.

Supraspinal modulation of neuronal synchronization by nociceptive stimulation induces an enduring reorganization of dorsal horn neuronal connectivity.

KEY POINTS: The state of central sensitization induced by the intradermic injection of capsaicin leads to structured (non-random) changes in functional connectivity between dorsal horn neuronal populations distributed along the spinal lumbar segments in anaesthetized cats. The capsaicin-induced changes in neuronal connectivity and the concurrent increase in secondary hyperalgesia are transiently reversed by the systemic administration of small doses of lidocaine, a clinically effective procedure to treat neuropathic pain. The effects of both capsaicin and lidocaine are greatly attenuated in spinalized preparations, showing that supraspinal influences play a significant role in the shaping of nociceptive-induced changes in dorsal horn functional neuronal connectivity. We conclude that changes in functional connectivity between segmental populations of dorsal horn neurones induced by capsaicin and lidocaine result from a cooperative adaptive interaction between supraspinal and spinal neuronal networks, a process that may have a relevant role in the pathogenesis of chronic pain and analgesia. ABSTRACT: Despite a profusion of information on the molecular and cellular mechanisms involved in the central sensitization produced by intense nociceptive stimulation, the changes in the patterns of functional connectivity between spinal neurones associated with the development of secondary hyperalgesia and allodynia remain largely unknown. Here we show that the state of central sensitization produced by the intradermal injection of capsaicin is associated with structured transformations in neuronal synchronization that lead to an enduring reorganization of the functional connectivity within a segmentally distributed ensemble of dorsal horn neurones. These changes are transiently reversed by the systemic administration of small doses of lidocaine, a clinically effective procedure to treat neuropathic pain. Lidocaine also reduces the capsaicin-induced facilitation of the spinal responses evoked by weak mechanical stimulation of the skin in the region of secondary but not primary hyperalgesia. The effects of both intradermic capsaicin and systemic lidocaine on the segmental correlation and coherence between ongoing cord dorsum potentials and on the responses evoked by tactile stimulation in the region of secondary hyperalgesia are greatly attenuated in spinalized preparations, showing that supraspinal influences are involved in the reorganization of the nociceptive-induced structured patterns of dorsal horn neuronal connectivity. We conclude that the structured reorganization of the functional connectivity between the dorsal horn neurones induced by capsaicin nociceptive stimulation results from cooperative interactions between supraspinal and spinal networks, a process that may have a relevant role in the shaping of the spinal state in the pathogenesis of chronic pain and analgesia.

Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform.

We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms. A number of shared differentially expressed genes and pathways between subAR and cAR in both platforms strongly suggest that these two clinical phenotypes form a continuum of alloimmune activation. SubAR is associated with fewer or less expressed genes than cAR in blood, whereas in biopsy tissues, this clinical phenotype demonstrates a more robust molecular signature for both platforms. The discovery work done in this study confirms a clear ability to detect gene expression profiles for sTx, subAR, and cAR in both blood and biopsy tissue, yielding equivalent predictive performance that is agnostic to both technology and platform. Our data also provide strong biological insights into the molecular mechanisms underlying these signatures, underscoring their logistical potential as molecular diagnostics to improve clinical outcomes following kidney transplantation.

Biomass fuel smoke exposure was associated with adverse cardiac remodeling and left ventricular dysfunction in Peru.

While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59 years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain.

Relationship between respiratory and food allergy and evaluation of preventive measures.

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions.

Different prognostic models for different patient populations: validation of a new prognostic model for patients with oropharyngeal cancer in Western Europe.

OBJECTIVE: The presence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant in prognostic risk modelling. Recently, a prognostic model was proposed in which HPV status, comorbidity and nodal stage were the most important prognostic factors to determine high-, intermediate- and low-risk survival groups. Here, we report on the validation of this model using an independent single-institutional cohort. METHODS: A total number of 235 patients curatively treated for OPSCC in the period 2000-2011 at the MUMC (Maastricht University Medical Center, The Netherlands) were included. The presence of an oncogenic HPV infection was determined by p16 immunostaining, followed by a high-risk HPV DNA PCR on the p16-positive cases. The model variables included were HPV status, comorbidity and nodal stage. As a measure of model performance, the Harrell's Concordance index (Harrell's C-index) was used. RESULTS: The 5-year overall survival (OS) estimates were 84.6%, 54.5% and 28.7% in the low-, intermediate- and high-risk group, respectively. The difference between the survival curves was highly significant (P<0.001). The Harrell's C-index was 0.69 (95% confidence interval (CI): 0.63-0.75). CONCLUSION: In this study a previously developed prognostic risk model was validated. This model will help to personalise treatment in OPSCC patients. This model is publicly available at www.predictcancer.org.

Nasal Hyperreactivity: Nonspecific Nasal Provocation Tests. Review by the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology.

Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity.

Consensus document on allergic conjunctivitis (DECA).

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Role of Rhizobium endoglucanase CelC2 in cellulose biosynthesis and biofilm formation on plant roots and abiotic surfaces.

BACKGROUND: The synthesis of cellulose is among the most important but poorly understood biochemical processes, especially in bacteria, due to its complexity and high degree of regulation. In this study, we analyzed both the production of cellulose by all known members of the Rhizobiaceae and the diversity of Rhizobium celABC operon predicted to be involved in cellulose biosynthesis. We also investigated the involvement in cellulose production and biofilm formation of celC gene encoding an endoglucanase (CelC2) that is required for canonical symbiotic root hair infection by Rhizobium leguminosarum bv. trifolii. RESULTS: ANU843 celC mutants lacking (ANU843ΔC2) or overproducing cellulase (ANU843C2+) produced greatly increased or reduced amounts of external cellulose micro fibrils, respectively. Calcofluor-stained cellulose micro fibrils were considerably longer when formed by ANU843ΔC2 bacteria rather than by the wild-type strain, in correlation with a significant increase in their flocculation in batch culture. In contrast, neither calcofluor-stained extracellular micro fibrils nor flocculation was detectable in ANU843C2+ cells. To clarify the role of cellulose synthesis in Rhizobium cell aggregation and attachment, we analyzed the ability of these mutants to produce biofilms on different surfaces. Alteration of wild-type CelC2 levels resulted in a reduced ability of bacteria to form biofilms both in abiotic surfaces and in planta. CONCLUSIONS: Our results support a key role of the CelC2 cellulase in cellulose biosynthesis by modulating the length of the cellulose fibrils that mediate firm adhesion among Rhizobium bacteria leading to biofilm formation. Rhizobium cellulose is an essential component of the biofilm polysaccharidic matrix architecture and either an excess or a defect of this "building material" seem to collapse the biofilm structure. These results position cellulose hydrolytic enzymes as excellent anti-biofilm candidates.

Trypanosoma cruzi discrete typing units in Chagas disease patients from endemic and non-endemic regions of Argentina.

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

Treatment for T1DM patients by a neuro-fuzzy inverse optimal controller including multi-step prediction.

Diabetes Mellitus is a serious metabolic condition for global health associations. Recently, the number of adults, adolescents and children who have developed Type 1 Diabetes Mellitus (T1DM) has increased as well as the mortality statistics related to this disease. For this reason, the scientific community has directed research in developing technologies to reduce T1DM complications. This contribution is related to a feedback control strategy for blood glucose management in population samples of ten virtual adult subjects, adolescents and children. This scheme focuses on the development of an inverse optimal control (IOC) proposal which is integrated by neural identification, a multi-step prediction (MSP) strategy, and Takagi-Sugeno (T-S) fuzzy inference to shape the convenient insulin infusion in the treatment of T1DM patients. The MSP makes it possible to estimate the glucose dynamics 15 min in advance; therefore, this estimation allows the Neuro-Fuzzy-IOC (NF-IOC) controller to react in advance to prevent hypoglycemic and hyperglycemic events. The T-S fuzzy membership functions are defined in such a way that the respective inferences change basal infusion rates for each patient's condition. The results achieved for scenarios simulated in Uva/Padova virtual software illustrate that this proposal is suitable to maintain blood glucose levels within normoglycemic values (70-115 mg/dL); furthermore, this level remains less than 250 mg/dL during the postprandial event. A comparison between a simple neural IOC (NIOC) and the proposed NF-IOC is carried out using the analysis for control variability named CVGA chart included in the Uva/Padova software. This analysis highlights the improvement of the NF-IOC treatment, proposed in this article, on the NIOC approach because each subject is located inside safe zones for the entire duration of the simulation.

Rhizobium cellulase CelC2 is essential for primary symbiotic infection of legume host roots.

The rhizobia-legume, root-nodule symbiosis provides the most efficient source of biologically fixed ammonia fertilizer for agricultural crops. Its development involves pathways of specificity, infectivity, and effectivity resulting from expressed traits of the bacterium and host plant. A key event of the infection process required for development of this root-nodule symbiosis is a highly localized, complete erosion of the plant cell wall through which the bacterial symbiont penetrates to establish a nitrogen-fixing, intracellular endosymbiotic state within the host. This process of wall degradation must be delicately balanced to avoid lysis and destruction of the host cell. Here, we describe the purification, biochemical characterization, molecular genetic analysis, biological activity, and symbiotic function of a cell-bound bacterial cellulase (CelC2) enzyme from Rhizobium leguminosarum bv. trifolii, the clover-nodulating endosymbiont. The purified enzyme can erode the noncrystalline tip of the white clover host root hair wall, making a localized hole of sufficient size to allow wild-type microsymbiont penetration. This CelC2 enzyme is not active on root hairs of the nonhost legume alfalfa. Microscopy analysis of the symbiotic phenotypes of the ANU843 wild type and CelC2 knockout mutant derivative revealed that this enzyme fulfils an essential role in the primary infection process required for development of the canonical nitrogen-fixing R. leguminosarum bv. trifolii-white clover symbiosis.

Legumes display common and host-specific responses to the rhizobial cellulase CelC2 during primary symbiotic infection.

Primary infection of legumes by rhizobia involves the controlled localized enzymatic breakdown of cell walls at root hair tips. Previous studies determined the role of rhizobial CelC2 cellulase in different steps of the symbiotic interaction Rhizobium leguminosarum-Trifolium repens. Recent findings also showed that CelC2 influences early signalling events in the Ensifer meliloti-Medicago truncatula interaction. Here, we have monitored the root hair phenotypes of two legume plants, T. repens and M. sativa, upon inoculation with strains of their cognate and non-cognate rhizobial species, R. leguminosarum bv trifolii and E. meliloti, (over)expressing the CelC2 coding gene, celC. Regardless of the host, CelC2 specifically elicited 'hole-on-the-tip' events (Hot phenotype) in the root hair apex, consistent with the role of this endoglucanase in eroding the noncrystalline cellulose found in polarly growing cell walls. Overproduction of CelC2 also increased root hair tip redirections (RaT phenotype) events in both cognate and non-cognate hosts. Interestingly, heterologous celC expression also induced non-canonical alterations in ROS (Reactive Oxygen Species) homeostasis at root hair tips of Trifolium and Medicago. These results suggest the concurrence of shared unspecific and host-related plant responses to CelC2 during early steps of symbiotic rhizobial infection. Our data thus identify CelC2 cellulase as an important determinant of events underlying early infection of the legume host by rhizobia.

The design of an observational study of hypertension management, adherence and pressure control in Blood Pressure Success Zone Program participants.

AIMS: The Blood Pressure Success Zone (BPSZ) Program, a nationwide initiative, provides education in addition to a complimentary trial of one of three antihypertensive medications. The BPSZ Longitudinal Observational Study of Success (BPSZ-BLISS) aims to evaluate blood pressure (BP) control, adherence, persistence and patient satisfaction in a representative subset of BPSZ Program participants. The BPSZ-BLISS study design is described here. METHODS: A total of 20,000 physicians were invited to participate in the study. Using a call centre supported Interactive Voice Response System (IVRS), physicians report BP and other data at enrolment and every usual care visit up to 12 +/- 2 months; subjects self-report BPs, persistence, adherence and treatment satisfaction at 3, 6 and 12 months post-BPSZ Program enrolment. In addition to BPSZ Program enrolment medications, physicians prescribe antihypertensive medications and schedule visits as per usual care. The General Electric Healthcare database will be used as an external reference. RESULTS: After 18 months, over 700 IRB approved physicians consented and enrolled 10,067 eligible subjects (48% male; mean age 56 years; 27% newly diagnosed); 97% of physicians and 78% of subjects successfully entered IVRS enrolment data. Automated IVRS validations have maintained data quality (< 5% error on key variables). Enrolment was closed 30 April 2007; study completion is scheduled for June 2008. CONCLUSIONS: The evaluation of large-scale health education programmes requires innovative methodologies and data management and quality control processes. The BPSZ-BLISS design can provide insights into the conceptualisation and planning of similar studies.

Measuring left ventricular mechanical dyssynchrony from ECG-gated SPECT myocardial perfusion imaging.

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. The traditional criteria to select patients for CRT (New York Heart Association [NYHA] class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) result in at least 30% of the selected patients with no response to CRT. Recent studies with echocardiography have shown that the presence of LV dyssynchrony is an important predictor for response to CRT. However, the recent report from the predictors of response to cardiac resynchronization therapy (PROSPECT) trial suggested that under ''real-world'' conditions the current available echocardiographic techniques including tissue Doppler imaging (TDI) and myocardial strain-rate imaging are not ready for routine clinical practice to assess LV dyssynchrony. Phase analysis is a recently developed technique that allows measuring LV dyssynchrony from electrocardiogram (ECG)-gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI). This technique uses Fourier harmonic functions to approximate regional wall thickening over the cardiac cycle and to calculate regional onset of mechanical contraction (OMC) phases. These OMC phases are obtained three-dimensionally over the entire left ventricle to quantitatively assess the degree of LV dyssynchrony. This technique has been compared to TDI and shown promising results in clinical validations. The advantages of this technique over echocardiography in measuring LV dyssynchrony are its automation, its high repeatability and reproducibility. It can be applied to any conventional GSPECT MPI study with no additional procedure. In this review the phase analysis methodology is described and its up-to-date clinical validations are summarized.

[Adenomatoid tumour of epididymis: the most common tumour of the paratesticular structures]. / Tumor adenomatoide de epididimo: el tumor más frecuente de las estructuras paratesticulares.

INTRODUCTION: Paratesticular tumours are rare but generally benign neoplasms, usually treated by local excission. Adenomatoid tumours of epididymis are the most common of these tumours. OBJECTIVES: Analyze paratesticular tumours treated in our center and describe dyagnosis and treatment of adenomatoid tumours of epididymis. MATERIAL AND METHODS: We retrospectively review 8 patients with paratesticular tumours treated from July 1997 to July 2007. We analyze clinical presentation, dyagnostic suspicion given by image technique, treatment followed and final dyagnosis. RESULTS: Patients median age was 44.1 years (22-69), presenting most of them subacute scrotal tumour with median size by ultrasound of 2.8 cm (1.5-7). All of them were locally extirpated except one with suspicion of a malignant polyorchidism and another one with an apparently intratesticular lesion of great size. Just in two cases peroperatory biopsy was performed. Dyagnosis was in 4 cases adenomatoid tumour of epididymis, in two cases fibrous pseudotumour of epididymis, in one case leiomyoma of epididymis and in one case angiolipoma of spermatic cord. Just in one case diagnosed of adenomatoid tumour of epididymis ultrasound confirmed solid tumour suggesting the final dyagnosis. CONCLUSIONS: Adenomatoid tumors of epididymis are rare tumours which may present at any age. Ultrasound may help in dyagnosis, but its capacity to distinguish this lesions is low. Benignity of adenomatoid tumour of epididymis as well as most of the other paratesticular tumours should make local excission the treatment of choice and, when any doubt existed, peroperatory biopsy should be performed.

Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

Increased rewarding properties of morphine in perinatally protein-malnourished rats.

In the current research, we assessed the influence of a protein malnutrition schedule from the 14th day of gestation up to 40 days of age (D-rats) on the rewarding properties of morphine in adult rats by means of the conditioned place preference paradigm. Well-nourished animals (C-rats) administered with different doses of morphine (0.75, 1.5, 3, 6, 12 or 24 mg/kg i.p.) exhibited a conditioning place preference with doses of 3 and 6 mg/kg, whereas in D-rats such a conditioning effect was observed with doses of 1.5 and 3 mg/kg. No adverse effects were observed in either C- or D-rats for the higher doses of morphine. In addition, when animals of both groups were pretreated twice a day for 3 days with increasing doses of morphine (5, 10 and 20 mg/kg s.c.), only D-rats elicited sensitization to the conditioning effect with the lowest dose of morphine (0.75 mg/kg i.p.). Furthermore, sensitized D-rats showed a selective and significant increase in FosB expression in the nucleus accumbens (core and shell), basolateral amygdala and medial prefrontal cortex, brain areas that are functionally related to the rewarding neural circuit. These results demonstrate that a deficient nutritional status during the perinatal period results in adult subjects having neural alterations, leading to an increased responsiveness to morphine and/or enhanced reinforcement effects, which correlates with an overexpression of FosB in selective brain areas related to the rewarding network.

[Case report. Patient with varicocele & oligozoospermia with Y chromosome microdeletion: AZFb+c]. / Aportación de un caso. Paciente con varicocele y oligozoospermia, con microdeleción en cromosoma Y: AZFb+c.

The 13-18% of the couples in reproductive age gets to present some kind of fertility problem, the male factor participates in near 50% of the cases. The microdeletions in the Yq chromosome occupy single the 7,6%; severe oligozoospermia and azoospermia are related with these alterations. The structure of region AZF of Yq is divided in AZFa, AZFb, AZFc and AZFd. The microdeletions can be simple or combined, the microdeletion AZFc (59-65%) is the commonest. In cases with severe oligozoospermia (or azoospermia), study of microdeletions in Y chromosome is suggested. ICSI with selection of sex, would be the treatment adapted in these cases, is in phase of study.

Insulin does not induce the hydrolysis of a glycosyl phosphatidylinositol in rat fetal hepatocytes.

An inositol phosphoglycan that is the polar head group of a glycosyl phosphatidylinositol has been considered as a putative mediator of insulin action. To gain insight into the functions of this hormone during development, the relationships between insulin, insulin receptors, glycosyl phosphatidylinositol, and inositol phosphoglycan were studied. Glycosyl phosphatidylinositol was isolated and characterized in fetal liver as early as day 15 of intrauterine life. In isolated hepatocytes from fetal and adult rats labeled with [3H]glucosamine, [3H]galactose, or [3H]myo-inositol, these molecules were incorporated into glycosyl phosphatidylinositol. In hepatocytes labeled with [3H]glucosamine and then allowed to react with [1-14C]IAI, the [3H]glycosyl phosphatidylinositol was purified as the 14C-labeled amidinated lipid. Glycosyl phosphatidylinositol molecules from fetal and adult cells were sensitive to hydrolysis by a phosphatidylinositol-specific phospholipase C from B. cereus. The product of this hydrolysis inhibits the activity of a cAMP-dependent protein kinase, whereas this effect was abolished by nitrous acid deamination. In isolated hepatocytes from adult animals, an inverse correlation between extracellular insulin and the number of insulin receptors and the cellular content of glycosyl phosphatidylinositol was observed. However, in fetal hepatocytes insulin failed to reduce the glycosyl-phosphatidylinositol content when labeled either with [1-14C]isethionyl acetimidate or [3H]glucosamine, whereas insulin-like growth factor I produced a significant hydrolysis of glycosyl phosphatidylinositol. Fetal and adult hepatocytes were incubated with insulin or inositol phosphoglycan after which glycogen phosphorylase activities were determined. Inositol phosphoglycan mimicked the action of insulin on both forms of the enzyme from adult hepatocytes, whereas in fetal cells insulin did not change, and purified inositol phosphoglycan reduced the activities of glycogen phosphorylase. These findings suggest a dissociation between insulin receptor occupancy and the expected hormonal effects in fetal hepatocytes. This could be related to alterations at a postreceptor level.