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PubMed1989

The nonoxime bispyridinium compound SAD-128 alters the kinetic properties of the nicotinic acetylcholine receptor ion channel: a possible mechanism for antidotal effects.

The effects of SAD-128 [1,1'-oxybis(methylene) bis 4-(1,1-dimethylethyl) pyridinium dichloride], a nonoxime bispyridinium compound, were investigated on the nicotinic acetylcholine receptor-ion channels of frog muscle fibers using end-plate current (EPC) and single channel current measurement techniques. SAD-128 decreased the EPC peak amplitude in a concentration-dependent manner and caused nonlinearity in the current-voltage plots. The time constant of EPC decay was prolonged by SAD-128 (10-200 microM) at potentials between +50 and -90 mV without loss of the single exponential decay. However, at -100 mV and below, biphasic decays of the EPCs were observed in the presence of the drug. The time constant of the fast phase of the EPC decay decreased, whereas that of the slow phase increased, with either hyperpolarization or increasing concentration of the drug. SAD-128 weakly inhibited acetylcholinesterase in frog sartorius muscle. At the single-channel current level, SAD-128 reduced the mean channel open time and produced a blocked state evidenced as an additional phase in the closed time distribution. The agent induced a biphasic burst time distribution whose fast component became faster and slow component slower with increasing concentration and hyperpolarization. The present study provides more details regarding the kinetics of the nicotinic acetylcholine receptor ion channel-blocking mechanisms and a correlation between single-channel currents and macroscopic events. The ability of SAD-128 to block the nicotinic acetylcholine receptor may underlie its efficacy in counteracting lethal effect of organophosphorus compounds.

Animals↗
PubMed1996

Modulation of erythrocyte potassium chloride cotransport, potassium content, and density by dietary magnesium intake in transgenic SAD mouse.

Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6 normal mice, we investigated the effect of 2 weeks of diet with either low Mg (6 +/- 2 mg/kg body weight/d) or high Mg (1,000 +/- 20 mg/kg body weight/ d), in comparison with a diet of standard Mg (400 +/- 20 mg/ kg body weight/d). The high-Mg diet increased SAD 1 erythrocyte Mg and K contents and reduced K-CI cotransport activity, mean corpuscular hemoglobin concentration (MCHC), cell density, and reticulocyte count. SAD 1 mice treated with low-Mg diet showed a significant reduction in erythrocyte Mg and K contents and increases in K-CI cotransport, MCHC, cell density, and reticulocyte counts. In SAD 1 mice, hematocrit (Hct) and hemoglobin (Hb) decreased significantly with low Mg diet and increased significantly with high-Mg diet. The C57BL/6 controls showed significant changes only in erythrocyte Mg and K content, and K-CI cotransport activities, similar to those observed in SAD 1 mice. Thus, in the SAD 1 mouse, changes in dietary Mg modulate K-CI cotransport, modify erythrocyte dehydration, and ultimately affect Hb levels.

Anemia, Sickle Cell↗
PubMed1996

Gender differences in regional cerebral blood flow during transient self-induced sadness or happiness.

Men, compared to women, are less likely to experience mood disorders. We wondered if gender differences exist in the ability to self-induce transient sadness and happiness, and in regional cerebral blood flow (rCBF) either at rest or during transient emotions. Ten adult men and 10 age-matched women, all healthy and never mentally ill, were scanned using H2(15)O positron emission tomography at rest and during happy, sad, and neutral states self-induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces. At rest, women had decreased temporal and prefrontal cortex rCBF, and increased brainstem rCBF. There were no significant between-group differences in difficulty, effort required, or the degree of happiness or sadness induced. Women activated a significantly wider portion of their limbic system than did men during transient sadness, despite similar self-reported changes in mood. These findings may aid in understanding gender differences with respect to emotion and mood.

Adult↗
PubMed2005

A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals.

BACKGROUND: The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals. RESULTS: Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals. CONCLUSIONS: These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.

Adult↗
PubMed2004

Childhood and adult sexual abuse, rumination on sadness, and dysphoria.

OBJECTIVE: The study addressed the hypothesis that adults reporting sexual abuse are more likely to exhibit a general tendency to ruminate on sadness. The relations between reported abuse, rumination on sadness, and dysphoria were also examined. METHOD: Undergraduate students (101 women and 100 men) reported on childhood and adult sexual abuse and instances of intimidation, as well as completing the Rumination on Sadness Scale [Journal of Personality Assessment 75 (2000) 404] and the Beck Depression Inventory [Depression: Clinical, Experimental, and Theoretical Aspects, Harper & Row, New York]. RESULTS: Participants who reported more abuse were more likely to report rumination on sadness. Both reports of abuse and of rumination were linked to dysphoria. Overall, causal modeling indicated that two models were equally effective in accounting for the data: (a) victimization leads to dysphoria, with this relation being partly mediated by rumination and (b) victimization leads to dysphoria, which in turn leads to rumination. Both models are consistent with prior research. For men considered separately, both models were equally effective. For women, model a best accounted for the data. CONCLUSION: One of the pathways by which victimization may lead to depression in adulthood is by encouraging the development of a tendency to ruminate on sadness. Alternatively, victimization may lead to depression by other means, and the experienced depression or dysphoria may foster rumination.

Adult↗
PubMed2005

The neural bases of amusement and sadness: a comparison of block contrast and subject-specific emotion intensity regression approaches.

Neuroimaging studies have made substantial progress in elucidating the neural bases of emotion. However, few studies to date have directly addressed the subject-specific, time-varying nature of emotional responding. In the present study, we employed functional magnetic resonance imaging to examine the neural bases of two common emotions--amusement and sadness--using both (a) a stimulus-based block contrast approach and (b) a subject-specific regression analysis using continuous ratings of emotional intensity. Thirteen women viewed a set of nine 2-min amusing, sad, or neutral film clips two times. During the first viewing, participants watched the film stimuli. During the second viewing, they made continuous ratings of the intensity of their own amusement and sadness during the first film viewing. For sad films, both block contrast and subject-specific regression approaches resulted in activations in medial prefrontal cortex, inferior frontal gyrus, superior temporal gyrus, precuneus, lingual gyrus, amygdala, and thalamus. For amusing films, the subject-specific regression analysis demonstrated significant activations not detected by the block contrast in medial, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior cingulate, temporal lobes, hippocampus, thalamus, and caudate. These results suggest a relationship between emotion-specific temporal dynamics and the sensitivity of different data analytic methods for identifying emotion-related neural responses. These findings shed light on the neural bases of amusement and sadness, and highlight the value of using emotional film stimuli and subject-specific continuous emotion ratings to characterize the dynamic, time-varying components of emotional responses.

Adult↗
PubMed1991

[Mood follow-up over 6 years in a patient with season-dependent form of depression (SAD)].

Since the first description of seasonal affective disorder (SAD), many international studies have confirmed the existence of this subgroup of depressive patients. Even though the diagnosis of SAD has been incorporated into the DSM-III-R classification system, many psychiatrists maintain a certain skepsis as to the existence of SAD as a separate sub-group of depression. The diagnostic issues are important because of the apparent specificity of treatment of SAD with bright light. Most diagnoses have relied on retrospective descriptions of the patients' depressive and healthy phases with respect to time of year. We present prospectively gathered weekly depression self-ratings in a SAD patient over a period of six years that may provide valid criteria for diagnostic purposes. This is a particularly exemplary case with implications for the relationship between light therapy and the course of depressive phases, the possible interaction of light treatment with lithium, the relationship between weight-changes and mood changes over the year and aspects of family loading of the illness.

Affective Symptoms↗
PubMed1997

Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.

OBJECTIVE: To describe the psychometric properties of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) interview, which surveys additional disorders not assessed in prior K-SADS, contains improved probes and anchor points, includes diagnosis-specific impairment ratings, generates DSM-III-R and DSM-IV diagnoses, and divides symptoms surveyed into a screening interview and five diagnostic supplements. METHOD: Subjects were 55 psychiatric outpatients and 11 normal controls (aged 7 through 17 years). Both parents and children were used as informants. Concurrent validity of the screen criteria and the K-SADS-PL diagnoses was assessed against standard self-report scales. Interrater (n = 15) and test-retest (n = 20) reliability data were also collected (mean retest interval: 18 days; range: 2 to 36 days). RESULTS: Rating scale data support the concurrent validity of screens and K-SADS-PL diagnoses. Interrater agreement in scoring screens and diagnoses was high (range: 93% to 100%). Test-retest reliability kappa coefficients were in the excellent range for present and/or lifetime diagnoses of major depression, any bipolar, generalized anxiety, conduct, and oppositional defiant disorder (.77 to 1.00) and in the good range for present diagnoses of posttraumatic stress disorder and attention-deficit hyperactivity disorder (.63 to .67). CONCLUSION: Results suggest the K-SADS-PL generates reliable and valid child psychiatric diagnoses.

Adolescent↗
PubMedDate not supplied

Endocrine correlates of sadness and elation.

In a series of three exploratory studies, we examined the endocrine correlates of elation and sadness produced by the Velten Mood Induction Procedure (VMIP). In Study 1, 10 college females participated in elation and sadness mood inductions on separate days. In Study 2, 12 college females participated in a neutral mood induction. In Study 3, 16 college-aged actresses participated in elation and sadness mood inductions as in Study 1. At regular intervals in each study, we assessed subjective ratings of emotions, serum cortisol and growth hormone, and heart rate and blood pressure. Results demonstrated that the VMIP induced the desired moods. Serum cortisol increased equally in response to both the sadness and elation mood inductions, but showed no change in response to the neutral mood induction. Select associations between affect and cortisol levels were also observed. Interestingly, our data from Study 3 also suggest that an association may exist between elation and growth hormone. These endocrine changes did not appear to be a function of general arousal as indexed by cardiovascular changes. We conclude that elation and sadness are associated with endocrine concomitants and that the VMIP is a viable method for examining such associations. These previously unreported affect-endocrine relationships are discussed and implications for psychobiological theories of emotion are considered.

Adolescent↗
PubMed2006

Predicting the onset of emotional recovery following nonmarital relationship dissolution: survival analyses of sadness and anger.

Event onset modeling was used to investigate the time course of breakup-related affective processes. Daily emotion data were collected for 4 weeks from 58 young adults who recently experienced the dissolution of a serious romantic relationship. Using baseline data obtained from individuals in intact dating relationships, sadness and anger recovery were defined as points in time and then modeled as a function of theoretically relevant predictors using Cox's survival analysis. Acceptance of relationship termination mediated the association between attachment security and sadness recovery. Greater levels of love, anger, and attachment preoccupation were associated with a decreased probability of sadness recovery during the study period. Attachment security was associated with an increased probability of anger recovery, whereas ongoing sadness decreased the probability of this event. Discussion centers on the differential functioning of sadness and anger as well as the need to consider emotional change as a multicomponent process.

Adaptation, Psychological↗
PubMed2026

Rab10 coordinates SADS-CoV non-lytic egress through the ERGIC-TGN-lysosome trafficking pathway.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a bat-originated alphacoronavirus that causes devastating enteric disease in neonatal piglets and possesses significant potential for cross-species transmission. While the early stages of the coronavirus life cycle have been extensively characterized, the host factors indispensable for virion assembly and subsequent export remain largely enigmatic. Here, by performing a genome-wide CRISPR-Cas9 knockout screen using a recombinant icSADS-CoV-GFP reporter virus, we identified the small GTPase Rab10 as a critical host dependency factor for SADS-CoV infection. Viral life cycle analysis revealed that Rab10 is not required for viral attachment, entry, or initial genome replication, but is essential for the virion transport and non-lytic egress. Rab10 deficiency markedly reduced the extracellular release of viral RNA, viral proteins, and infectious progeny, as well as the secretion of SADS-CoV virus-like particles. Confocal imaging showed that Rab10 and viral protein-positive intracellular structures were associated with LMAN1, TGN46, and LAMP1 positive compartments. These findings support a model in which Rab10 coordinates a virus-containing vesicles trafficking pathway associated with ERGIC-TGN-lysosome compartments. Mechanistically, Rab10 facilitates the loading of the viral envelope (E) protein into transport vesicles derived from the ERGIC. Rab10 associates with the SADS-CoV E protein, and mapping analyses implicated the C-terminal PDZ-binding motif, particularly residue V75, in efficient Rab10 association and viral release. Collectively, our findings identify Rab10 as a host regulator of SADS-CoV non-lytic egress and highlight the E-Rab10 interaction and the vesicular trafficking machinery as a potential target for developing antiviral strategies.

Animals↗
PubMed2001

Comparative immunogenicity and efficacy studies with oral rabies virus vaccine SAD P5/88 in raccoon dogs and red foxes.

A comparative study of immunogenicity and efficacy of the oral rabies virus vaccine SAD P5/88 in raccoon dogs and foxes was conducted. The raccoon dogs received 10(6.9) (n = 6), 10(6.3) (n = 6) or 10(5.7) FFU SAD P5/88 (n = 5) by direct oral application, and subsequently all animals seroconverted. The foxes received 10(7.2) (n = 4), 10(6.2) (n = 4), 10(5.2) (n = 4) and 10(4.2) FFU SAD P5/88 (n = 5) by the same route. On days 106 and 196 post vaccination 10 raccoon dogs and 16 foxes were challenged with a relevant street virus, respectively. All 10 raccoon dogs vaccinated with 10(6.3) (n = 5) or 10(5.7) FFU SAD P5/88 (n = 5) survived the challenge, whereas all control animals (n = 5) died of rabies. Two foxes vaccinated with 10(4.2) FFU and one fox vaccinated with 10(5.2) FFU died of rabies on day 7, 17 and 12 post infection, respectively. Also all control foxes succumbed to rabies. Our findings demonstrate that SAD P5/88 is not only an effective vaccine for oral vaccination of foxes but also for that of raccoon dogs.

Administration, Oral↗
PubMed1989

Oral vaccination of raccoons (Procyon lotor) with an attenuated (SAD-B19) rabies virus vaccine.

Unlike previous reports to the contrary, raccoons (Procyon lotor) were successfully vaccinated against rabies with a liquid SAD-B19 attenuated virus vaccine administered per os and given in vaccine-laden baits. There was neither evidence of vaccine-induced rabies in raccoons nor in a limited safety trial with opossums (Didelphis virginiana) given SAD-B19. Protection from lethal street rabies virus infection was not absolute: only three of nine raccoons given 1 x 10(6.0) TCID/ml were protected versus five of 10 raccoons given 1 x 10(7.0) TCID/ml of SAD-B19 and challenged 4 mo after consumption of vaccine-laden baits. Six of eight raccoons consuming 1 x 10(8.8) TCID/ml of SAD-B19 vaccine in baits survived street rabies virus challenge 2 mo postvaccination. Raccoon survivorship was not wholly dependent upon rabies virus-neutralizing antibody titer on the day of challenge. Vaccinated raccoons demonstrated a prominent anamnestic response within 1 wk following challenge. Surviving raccoons were observed for a minimum of 3 mo following street rabies virus challenge with neither clinical nor pathologic evidence of rabies. The SAD-B19 rabies vaccine administered within baits in captivity appears less effective for raccoons than for its demonstrated efficacy in the immunization of free-ranging foxes (Vulpes vulpes) in Europe.

Administration, Oral↗
PubMed2001

Can people feel happy and sad at the same time?

The authors investigated whether people can feel happy and sad at the same time. J. A. Russell and J. M. Carroll's (1999) circumplex model holds that happiness and sadness are polar opposites and, thus, mutually exclusive. In contrast, the evaluative space model (J. T. Cacioppo & G. G. Berntson, 1994) proposes that positive and negative affect are separable and that mixed feelings of happiness and sadness can co-occur. The authors both replicated and extended past research by showing that whereas most participants surveyed in typical situations felt either happy or sad, many participants surveyed immediately after watching the film Life Is Beautiful, moving out of their dormitories, or graduating from college felt both happy and sad. Results suggest that although affective experience may typically be bipolar, the underlying processes, and occasionally the resulting experience of emotion, are better characterized as bivariate.

Adolescent↗
PubMed2002

On being sad and mistaken: mood effects on the accuracy of thin-slice judgments.

A series of studies explored how sadness impacts the accuracy of social judgments. In Study 1, induced sadness led to reduced accuracy in judgments of teacher effectiveness from brief samples of nonverbal behavior (thin slices). In Study 2, sad participants showed reduced accuracy in judging relationship type from thin slices as well as diminished judgmental efficiency. Study 3 revealed that higher Beck Depression Inventory scores were associated with diminished accuracy on the Profile of Nonverbal Sensitivity. Finally, Study 4 tested the possibility that sadness impairs accuracy by promoting a more deliberative information-processing style. As expected, accuracy was higher among participants in a sad mood condition who completed the judgment task while simultaneously performing a distracting cognitive load task.

Affect↗
PubMed1990

Towards a mouse model for sickle cell disease: HB SAD.

Very recently a high expression of human hemoglobin S, which causes sickle cell disease, has been obtained in transgenic mice. We have constructed a modified beta S gene, beta SAD which carries two additional mutations in order to induce polymerization of transgenic hemoglobin when diluted by endogenous mouse Hb. The transgenic SAD mice are not anemic but exhibit a low percentage of irreversible sickle cells. Sickling is induced by deoxygenation of erythrocytes in vitro. In addition, the anemia of neonates and the low incidence of SAD animals in the progeny suggest a deleterious effect of SAD Hb during development. Finally, hypoxia induces a high mortality in SAD adults suggesting the induction of vaso-occlusive events.

Anemia, Sickle Cell↗
PubMedDate not supplied

[Development of orthopedics and founding of the Clinic for Orthopedic Surgery and Traumatology in Novi Sad].

A study of the development of the orthopaedic surgery in Novi Sad from the antique times till 1980 when the Clinic for Orthopaedic. Surgery and Traumatology was established has been carried out. Development from Roman Times till the Second World War. The first material evidence of the surgical activities in this area originates from the epoch of the Roman Empire, when under the emperor Augustus (Augustus, 27 B.C.-14 A.D.), the northern border of the Empire was established and fortified on the river Danube. At that time on the place of the contemporary Petrovaradin Fortress, a small fortification with a permanent garrison, called Cusum, was built. As it was proved by excavation of the surgical instruments from the Roman time at the nearby Sremska Mitrovica (Sirmium) the surgery in the Roman legions was quite developed and it could be concluded that some forms of surgery and orthopaedics were practised in the antique Cusum as well. There is no reliable evidence about the health service in the area after the Roman era till the 1689 when Petrovaradin was finally sized by Austrian troops from the Turks, and when the first recorded hospital (Petrovaradin Military Hospital) in this region was founded. At that time on the northern shore of the river Danube a new settlement, developing later into the town of Novi Sad, was established. Surgery together with orthopaedics at that time were performed by the so-called "feldschers", and then by primitive, self-taught surgeons who were actually experienced barbers, while educated doctors started to practice surgery only in the 19th century when the first surgical department in Novi Sad was founded in the Great Town Hospital, and for years after that, the orthopaedics was practised by general surgeons. The foundation of the Anglo-Yugoslav Children's Hospital for Tuberculosis of the Bones and Joints at Sremska Kamenica in 1934 by Dr. Katherine S. Macphail, a great benefactress of our people, was of great importance for the development of orthopaedics in this area as it was the first orthopaedic hospital in the country. The first small unit for orthopaedics, as a part of the Surgical Department of the Novi Sad State Hospital, was established in 1937 and led by a surgeon, Dr. Nikola Pravdica. Development from the Second World War till the 1980. After the Second World War the Main Provincial Hospital with two surgical departments was established in Novi Sad. At the so-called Second Surgical Department led by Dr. Nestor Teodorovic a small unit for traumatology and orthopaedics was founded in 1946, which functioned as such till 1953. The first properly trained orthopaedic surgeon was Dr. Stojan Letic who passed the specialty exam in 1953 and was attached to the Second Surgical Department of the Main Provincial Hospital. The first independent Orthopaedic and Traumatologic Department, led by an experienced orthopaedic surgeon, Dr. Vladimir Razenj, was established in 1956. From 1959 till 1963 the department was led by Prim. Dr. Dobrivoje Gradistanac. In 1963 this department together with the former "English Hospital" at Sremska Kamenica were incorporated into the so-called Clinic for Surgical Diseases and divided in the Orthopaedic (led by Prof. Milenko Dosen) and separated Traumatologic (led by Prim. Stojan Letić) departments which existed as such till 1975 when they were integrated again into a single unit which evolved into the Clinic for Orthopaedic Surgery and Traumatology in 1980.

Health Facilities↗
PubMed1996

Effects of self-generated sad mood on regional cerebral activity: a PET study in normal subjects.

This study investigated the cerebral regions modulated by self-generated sad mood in normal subjects. Eleven healthy men experienced a temporary sad mood by recalling sad personal memories. Two control states were used for comparison: a resting condition, and a condition involving the recall of affectively neutral personal events. Regional cerebral blood flow (rCBF) images were obtained using [15O]-H2O Positron Emission Tomography. A statistical comparison of the images during negative mood and neutral recall conditions revealed that sad mood was associated with a decrease in rCBF in the left dorsolateral prefrontal, left medial prefrontal, and left temporal cortex; no increase in activity was noted in this comparison. Our results are consistent with the noted left prefrontal decrease in metabolism found in depressed patients through a variety of methodologies; however, our results contrast with findings of increased left or bilateral prefrontal activity in transient induced negative mood states reported for women (George et al., 1995, Am J Psychiatry 152:341-341) and for mixed-gender (Pardo et al., 1993, Am J Psychiatry 150:713-719) subject groups. The study brings to light a number of methodological issues, including the crucial importance of the baseline condition used for the isolation of the emotional components of a given task.

Adult↗