Orienting and classical conditioning in the rabbit (Oryctolagus cuniculus): effects of septal area lesions

Rabbits with either sham or septal lesions recieved differential classical conditioning training in which tones of different frequencies served as CSs and paraorbital shock served as the UCS. Eyeblink (EB), EMG, and heart rate (HR) CRs were concommitantly assessed. Free field activity was also studied in selected animals. Animals with septal lesions revealed an impaired EB discrimination which resulted from increased responding to the CS-. These animals showed HR CRs of greater magnitude than sham animals. The HR discrimination was, however, unimpaired by septal lesions. Differential EMG activity also occurred, but was unaffected by septal destruction. Septal lesions resulted in greater free-field activity associated with visual stimulation, but no differences were obtained between septal and sham animals in the dark. It is suggested that these results were due to an enhanced reactivity to environmental stimulation, possibly related to dysfunctions of the orienting reflex.     

Blood Pressure and Heart Rate Changes Accompanying Classical Eyeblink Conditioning In The Rabbit (Oryctolagus Cuniculus)

In two experiments employing 38 rabbits differential classical conditioning of heart rate, blood pressure, and corneoretinal potential (CRP) response were examined using l-sec and 4-sec interstimulus intervals ISI respectively. The conditioned response consisted of HK decelerations and DP depressor responses early in conditioning. However, many, but not all, animals revealed pressor responses and HR accelerations after the CRP discrimination was acquired. Significant correlations were also obtained between BP pressor responses, HR accelerations, and the frequency of CRP CRs. These results were discussed within the context of the orienting and defense reflexes.     

Evidence for a genetic association between alleles of monoamine oxidase a gene and bipolar affective disorder

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant. © 1995 Wiley-Liss, Inc.     

Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine

The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix’s extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.     

Implementation of the NCAA Sickle Cell Trait Screening Policy: A Survey of Athletic Staff and Student-athletes

Objective

To describe the perspectives and experiences of athletic trainers, coaches, and student-athletes approximately three years post-implementation of the NCAA sickle cell trait (SCT) screening policy.

Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4(+) T helper (Th) cell responses by gamma interferon (IFN-gamma)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-gamma-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.     

Familial gastric cancer: overview and guidelines for management

Families with autosomal dominant inherited predisposition to gastric cancer have been described. More recently, germline E-cadherin/CDH1 mutations have been identified in hereditary diffuse gastric cancer kindred. The need to have protocols to manage and counsel these families in the clinic led a group of geneticists, gastroenterologists, surgeons, oncologists, pathologists, and molecular biologists to convene a workshop to produce consensus statements and guidelines for familial gastric cancer. Review of the available cancer pathology from people belonging to families with documented germline E-cadherin/CDH1 mutations confirmed that the gastric cancers were all of the diffuse type. Criteria to define the different types of familial gastric cancer syndromes were agreed. Foremost among these criteria was that review of histopathology should be part of the evaluation of any family with aggregation of gastric cancer cases. Guidelines for genetic testing and counselling in hereditary diffuse gastric cancer were produced. Finally, a proposed strategy for clinical management in families with high penetrance autosomal dominant predisposition to gastric cancer was defined.     

Knowledge,attitude and behaviour regarding dietary salt intake among medical students in Angola

High salt (sodium chloride) consumption is an important determinant of high blood pressure and cardiovascular risk. According to World Health Organisation (WHO) statistics, over 80% of cardiovascular disease (CVD) deaths take place in low-and middle-income countries, and elevated blood pressure levels were a major cause of these CVD deaths in those countries.1 Lifestyle factors such as unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol have been considered the most important behavioural risk factors for heart disease and stroke.2Among dietary factors, high salt intake has been the most strongly associated with raised blood pressure and increased risk of stroke and CVD.3 Therefore dietary sodium restriction has been recommended as a non-pharmacological approach to blood pressure lowering,4-6 and for the prevention and control of non-communicable diseases at the population level.7,8Cumulative evidence has shown that even a modest reduction in salt intake was associated with blood pressure lowering and therefore with a significant reduction in incidence of cardiovascular events.9-12 Furthermore, data from the most recent systematic review and meta-analyses has shown the benefit of lowering sodium intake in apparently healthy adults and children,13 and in both hypertensive and normotensive individuals, irrespective of gender and ethnic group.9Since hypertension is associated with CVD worldwide, a public health intervention to reduce high blood pressure must target the role of lifestyle, particularly reduced sodium intake.7 Therefore, several countries have initiated strategies to reduce dietary salt intake in the general population by a combination of various procedures such as public education, food labelling, and collaboration with the food industry to reduce the salt content of processed food.14Among sub-Saharan African countries, only Nigeria and South Africa have developed dietary guidelines regarding salt intake.15 Recently, the South African government implemented important specific legislation towards decreasing salt intake in the population by reducing sodium content of processed foods by industries.16 Therefore, the current public health recommendation is that countries should launch national initiatives to reduce the over-consumption of salt as part of non-communicable disease prevention and healthy nutrition policies for limiting salt intake to less than 5 g/day for the general population including children.7 Despite of this guideline, however, high sodium intake remains prevalent around the world, with average daily salt intake varying from 5 to 18 g/day per person.17Although processed foods have been found to be the principal source of excessive dietary salt intake,18 sources of dietary sodium vary largely worldwide and may be influenced by cultural context and dietary habits of the population.19 In sub-Saharan African countries experiencing demographic and epidemiological transition, the rapid rise in prevalence of CVD (chiefly hypertension) has been attributed to lifestyle change, including high dietary sodium intake.20,21 However, consistent data from studies on risk factors are lacking for the majority of these countries.With regard to Angola, available data from a cross-sectional study reported a high prevalence of multiple cardiovascular risk factors, such as hypertension, sedentary lifestyle, electrocardiographic left ventricular hypertrophy,22 and high rate of the metabolic syndrome23 in an apparently healthy middle-aged population of university public employees living in urban and peri-urban areas.Determining the level of sodium intake in the population is crucial to establish intervention strategies and policy on reduction of sodium intake. For medical students in particular, it is very important to assess their awareness regarding dietary salt intake, since they are the future providers of healthcare information for the counselling of people about the need to reduce salt consumption. The aim of this study was to determine salt intake and to assess the knowledge, attitude and behaviour regarding dietary salt among medical students.     

From the Cover: Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.Obesity and the metabolic syndrome are major risk factors for a wide array of diseases, including type 2 diabetes mellitus, cardiovascular disease, and cancer (1, 2). Compelling evidence shows that metabolic syndrome is caused, in part, by a suboptimal intrauterine environment (3). The strong association between maternal obesity during pregnancy and metabolic syndrome in childhood is of particular concern because almost two-thirds of American women now enter pregnancy either overweight or obese (4). Obesity during pregnancy therefore creates a vicious, detrimental cycle of intrauterine transmission of metabolic disease from the mother to her children (5). Intervention strategies involving lifestyle changes or antiobesity drugs remain largely unsuccessful, and it is therefore urgent to explore the possibility of intervening in utero to prevent the development of obesity and metabolic syndrome.Obesity in pregnant women is associated with activation of placental insulin and mechanistic target of rapamycin complex 1 (mTORC1) signaling, up-regulation of specific placental amino acid transporters, and fetal overgrowth (6, 7). In addition, circulating levels of adiponectin (ADN) are decreased in obese pregnant women (8, 9). The ADN protein is synthesized in adipose tissue and undergoes tightly regulated multimerization involving chaperone proteins, including disulfide-bond A oxidoreductase-like protein (DsbA-L), resulting in the assembly of oligomeric ADN proteins of different molecular weight (10). Multimerization into the high-molecular-weight (HMW) form increases the t_1/2 of ADN (11), and the insulin-sensitizing effect of ADN can largely be attributed to the HMW form (12). Low circulating levels of HMW ADN strongly predict the development of gestational diabetes mellitus (GDM) independent of maternal adiposity (13, 14).We recently reported that ADN, in contrast to its well-known insulin-sensitizing effects in skeletal muscle and liver, inhibits insulin and mTORC1 signaling and amino acid transport in cultured primary human trophoblast (PHT) cells (15) and in pregnant mice in vivo (16). This effect is mediated by activation of trophoblast peroxisome proliferator-activated receptor-α (PPARα) signaling and increased ceramide synthesis, resulting in inhibition of IRS-1 (17). Thus, low circulating ADN in maternal obesity may be causally linked to changes in placental function and increased fetal growth. These findings, together with the recent discovery of an orally active ADN receptor agonist (AdipoRon) (18), provide the rationale for exploring the possibility that maternal ADN supplementation may prevent the adverse fetal outcomes in maternal obesity.We recently established a mouse model of obesity in pregnancy, which shows extensive similarities to the human condition, including low maternal ADN and glucose intolerance, increased placental nutrient transport, and fetal overgrowth (19). In this study, we used this model to test the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin signaling and nutrient transport, and prevents fetal overgrowth.