Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways.

The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic agent paraquat. Although survival to a high paraquat concentration (20 mM) was specifically increased in female flies only, locomotor activity and survival could be rescued in both male and female animals when exposed to lower paraquat levels (5 mM). These effects are dependent on the autophagic machinery, as Spd failed to confer resistance to paraquat-induced toxicity and locomotor impairment in flies deleted for the essential autophagic regulator ATG7 (autophagy-related gene 7). Spd treatment did also protect against mild doses of another oxidative stressor, hydrogen peroxide, but in this case in an autophagy-independent manner. Altogether, this study establishes that the protective effects of Spd can be exerted through different pathways that depending on the oxidative stress scenario do or do not involve autophagy.

The propeptide of yeast cathepsin D inhibits programmed necrosis.

The lysosomal endoprotease cathepsin D (CatD) is an essential player in general protein turnover and specific peptide processing. CatD-deficiency is associated with neurodegenerative diseases, whereas elevated CatD levels correlate with tumor malignancy and cancer cell survival. Here, we show that the CatD ortholog of the budding yeast Saccharomyces cerevisiae (Pep4p) harbors a dual cytoprotective function, composed of an anti-apoptotic part, conferred by its proteolytic capacity, and an anti-necrotic part, which resides in the protein's proteolytically inactive propeptide. Thus, deletion of PEP4 resulted in both apoptotic and necrotic cell death during chronological aging. Conversely, prolonged overexpression of Pep4p extended chronological lifespan specifically through the protein's anti-necrotic function. This function, which triggered histone hypoacetylation, was dependent on polyamine biosynthesis and was exerted via enhanced intracellular levels of putrescine, spermidine and its precursor S-adenosyl-methionine. Altogether, these data discriminate two pro-survival functions of yeast CatD and provide first insight into the physiological regulation of programmed necrosis in yeast.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding.

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding

The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33 percent of the newborns presented weak sucking, 23 percent slow rhythm, 30 percent absence of at least one adaptive oral reflex, and 14 percent with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100 percent. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.

An unusual cause of recurrent abdominal pain.

Abdominal pain is a common complaint with diverse etiologies. We describe an unusual case of recurrent abdominal pain in an adult due to lead poisoning, a condition usually associated with childhood. A previously healthy 42-yr-old man presented with 2 days of severe crampy abdominal pain and a 1-month history of constipation. Physical examination was remarkable for diffuse abdominal pain but peritoneal signs were not present. Blood tests were remarkable for hematocrit of 33 and mean cell volume of 78, with ovalocytes and basophilic stippling on blood smear. Abdominal x-ray showed stool throughout the colon and a nonspecific bowel gas pattern. The patient was treated with intravenous fluids and enemas, and his symptoms resolved within 2 days. Repeat history taking revealed he had been stripping paint from an old Victorian house in the preceding few months. He was discharged after a blood lead level was obtained. Before his clinic appointment he was readmitted 2 days later with recurrent abdominal pain. His blood lead level was elevated at 110 microg/dl (toxic range). After consultation with the Occupational Health and Safety Administration and local poison control service, he was treated with intravenous calcium edetate disodium and intramuscular dimercaprol. He was asymptomatic at discharge, with a level of 56 microg/dl. Two weeks later, a repeat level was elevated at 72 microg/dl, for which he received a 3-wk course of oral dimercaptosuccimer. Subsequent levels were unremarkable, and the patient remains asymptomatic. Abdominal pain secondary to lead poisoning in adults is uncommon. This case highlights the importance of taking a detailed occupational history and appropriately using "routine" blood tests to diagnose a rare condition that presented with a common complaint.

Adolescent schoolboys in SED classes: implications for child psychiatry.

OBJECTIVE: The primary purpose of this study was to determine basic psychosocial characteristics for adolescent socially and emotionally disturbed (SED) boys. METHODS: Boys aged 12 to 16 years who were recommended for SED placement were compared with same-aged boys recommended for other educational intervention. The main measures were the Kiddie SADS-E interview and Achenbach's parent Child Behavior Checklist and Teacher Report Form scales. RESULTS: The adolescent SED boys were found to have normal intelligence, high rates of family stressors, predominantly DSM-III externalizing disorders, serious dysfunction according to checklist ratings by both teachers and parents, and little current community mental health intervention. They were significantly different from the comparison group on several variables: lower socioeconomic status, more abuse experience, greater diagnostic comorbidity, higher Axis V clinician ratings, and higher teacher ratings on externalizing scales. CONCLUSIONS: Findings are similar to those for other age-gender groups of SED students. One implication is the need for more private child psychiatrists to become involved in the collaborative treatment of this complex and seriously ill group of special education students. Consequently, a second implication is to increase the experience of child psychiatry trainees in dealing with the many consultative needs of SED students and staff.

Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0.3 ppm nitrogen dioxide.

Symptoms and changes in pulmonary function of subjects with chronic obstructive pulmonary disease (COPD) and elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using a double-blind, crossover design with purified air. The 5-day experimental protocol required approximately 2 wk with at least a 5-day separation between randomized 4-h exposures to either NO2 or air which included several periods of exercise. Over a 2-yr period, COPD subjects, all with a history of smoking, consisting of 13 men and 7 women (mean age of 60.0 yr) and 20 elderly normal subjects of comparable age and sex were evaluated. During intermittent light exercise, COPD subjects demonstrated progressive decrements in FVC and FEV1 compared with baseline with 0.3 ppm NO2, but not with air. Differences in percent changes from baseline data (air-NO2) showed an equivocal reduction in FVC by repeated measures of analysis of variance and cross-over t tests (p less than 0.10). Subgroup analyses suggested that responsiveness to NO2 decreased with severity of COPD; in elderly normal subjects, NO2-induced reduction in FEV1 was greater among smokers than never-smokers. A comparison of COPD and elderly normal subjects also revealed distinctions in NO2-induced responsiveness.

Acute respiratory distress syndrome with pulmonary calcification in two patients with B cell malignancies.

Two patients, one with B cell lymphoma and hypercalcemia and the other with multiple myeloma and hypercalcemia developed acute progressive respiratory insufficiency characteristic of the adult respiratory distress syndrome (ARDS). Both were intubated and placed on mechanical ventilation. Lung compliance deteriorated and became refractory to mechanical inflation. Examination of the lungs at post mortem examination disclosed widespread calcification within alveolar septa and diffuse alveolar damage with hyaline membrane formation consistent with ARDS. Although ARDS has been described with lymphomatous involvement of the lungs, its development in association with metastatic calcification in B cell malignancy has not been previously reported.

Inhalation of 0.30 ppm nitrogen dioxide potentiates exercise-induced bronchospasm in asthmatics.

Epidemiologic studies support an association among elevated levels of nitrogen dioxide (NO2), increased respiratory symptoms, and alterations in lung function. To determine if low level NO2 inhalation potentiates exercise-induced bronchospasm, 15 asthmatic subjects, defined by airway constriction with cold air provocation, inhaled 0.30 ppm (560 micrograms/m3) NO2 for 30 min. All asthmatics inhaled either air or 0.30 ppm NO2 via a mouthpiece for 20 min at rest followed by 10 min of exercise on a bicycle ergometer at a workload of 300 kpm/min, producing a 3-fold or greater increase in minute ventilation. Our studies showed 72 +/- 2 (SE)% deposition of inhaled NO2 at rest and 87 +/- 1% deposition with exercise (p less than 0.001). Nitrogen dioxide inhalation at rest resulted in no significant change in pulmonary function. Nitrogen dioxide inhalation plus exercise compared to control (air) exposure plus exercise produced significantly greater reductions in FEV (p less than 0.01) and partial expiratory flow rates at 60% of total lung capacity (p less than 0.05). One hour after completion of NO2 exposure and exercise, pulmonary function had returned to baseline values. To determine if NO2 exposure caused increased reactivity to a known bronchoconstrictor, asthmatic subjects inhaled cold air (range: -11 +/- 2 degrees C) at 3 successive rates of isocapnic ventilation. The response to cold air was expressed as the respiratory heat exchange required to reduce the FEV by 10% (PD10RHE). Prior NO2 exposure potentiated the fall in FEV, PD10RHE, and specific airway conductance (p less than 0.05) after isocapnic cold air hyperventilation, compared to the control exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Silicosis in surface coalmine drillers.

Surface coalminers are generally thought to be at minimal risk of developing pneumoconiosis. Biopsy-proved silicoproteinosis was found in a 34-year-old surface coalmine driller, and two of nine other drill crew members who worked for the same company had chest radiographic findings compatible with simple silicosis. Reanalysis of data from a previous United States Public Health Service survey of surface coalminers, after exclusion of those with underground mining experience, showed that 38% of the cases of pneumoconiosis occurred in drill crew members, a group comprising only 11% of the study population. On the basis of these data surface coalmine drillers appear to have an increased risk of developing occupational lung disease.

Analysis of progesterone receptor binding in the ovine uterus.

The appropriate conditions for the measurement of ovine uterine cytoplasmic progesterone receptors (PR) have been determined to be 20 nM 3H-progesterone (3H-P4) with and without a 100-fold excess of non-radioactive progesterone (P4) 0-4 degrees C and 4 h of incubation. Under these conditions PR readily exchanged bound progesterone for progesterone added during the assay. This exchange occurred even when saturating concentrations of P4 were present. The progestins, R5020 and P4, effectively competed for the ovine uterine PR binding while non-progestin steroids and diethylstilbestrol failed to compete for the PR binding. The dissociation constant (Kd) measured for the 3H-P4 binding was 1.60 x 10-9 M indicating that the 3H-P4 binding was of high affinity. The levels of PR and the dissociation constant measured using 3H-R5020 in place of 3H-P4 were similar indicating a lack of corticosteroid binding globulin (CBG)-like binding in the ovine uterus.