Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period

Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks) of nutritional restriction by receiving the "regional basic diet" (RBD, with 8% protein) of low-income human populations of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD) was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23% protein, early malnourished rats showed deficits in body and brain weights (10% to 60% and 3% to 15%, respectively), as well as increases in velocity of SD propagation (10% to 20%). These effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 or 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD

Viscosity of gums in vitro and their ability to reduce postprandial hyperglycemia in normal subjects

Experiments were carried out in vitro with three viscous polysaccharides (guar gum, pectin, and carboxymethylcellulose (CMC)) of similar initial viscosity submitted to conditions that mimic events occurring in the stomach and duodenum, and their viscosity in these situations was compared to their actions on postprandial hyperglycemia in normal human subjects. Guar gum showed greater viscosity than the other gums during acidification and/or alkalinization and also showed larger effects on plasma glucose levels (35% reduction in maximum rise in plasma glucose) and on the total area under the curve of plasma glucose (control: 20,314 ± 1007 mg dl-1 180 min-1 vs guar gum: 18,277 ± 699 mg dl-1 180 min-1, P<0.01). Pectin, which showed a marked reduction in viscosity at 37oC and after events mimicking those that occur in the stomach and duodenum, did not have a significant effect on postprandial hyperglycemia. The performance of viscosity and the glycemia response to CMC were at an intermediate level between guar gum and pectin. In conclusion, these data suggest that temperature, the process of acidification, alkalinization and exposure to intestinal ions induce different viscosity changes in gums having similar initial viscosity, establishing a direct relationship between a minor decrease of gum viscosity in vitro and a reduction of postprandial hyperglycemia

Aversive stimulation during the stress-hyporesponsive period does not affect the number of corticotroph cells in neonatal male rats

Immunohistochemistry was used to evaluate the effects of neonatal handling and aversive stimulation during the first 10 days of life on the number of corticotrophs in the anterior lobe of the pituitary of 11-day-old male Wistar rats. Since adult rats handled during infancy respond with reduced corticosterone secretion in response to stressors and with less behavior inhibition in novel environments, we assumed that neonatal stimulation could affect pituitary morphology during this critical period of cell differentiation. Three groups of animals were studied: intact (no manipulation, N = 5), handled (N = 5) and stimulated (submitted to 3 different aversive stimuli, N = 5). The percentage of ACTH-immunoreactive cells in the anterior lobe of the pituitary (number of ACTH-stained cells divided by total number of cells) was determined by examining three slices per pituitary in which a minimum of 200 cells were counted by two independent researchers. Although animals during the neonatal period are less reactive to stress-like stimulation in terms of ACTH and corticosterone secretion, results showed that the relative number of ACTH-stained cells of neonatal handled (0.25 ± 0.01) and aversive stimulated (0.29 ± 0.03) rats was not significantly different from intact (0.30 ± 0.03) animals. Neonatal stimulation may have a differential effect on the various subpopulations of corticotroph cells in the anterior pituitary

The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis

In order to study the role of natural killer (NK) cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania) amazonensis (HSJD-1 strain). 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 106 spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 106 spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection.

Role of bradykinin in postprandial hypotension in humans

A transient significant decrease in mean arterial blood pressure (MAP) from 107 ± 3 to 98 ± 3 mmHg (P<0.05) was observed in elderly (59-69 years of age), healthy volunteers 25-30 min following ingestion of a test meal. In young volunteers (22-34 years of age), a postprandial decrease of MAP from 88 ± 3 to 83 ± 4 mmHg was also noted but it was not statistically significant. A 40% decrease in bradykinin (BK) content of circulatory high molecular weight kininogen had previously been observed in human subjects given the same test meal. We presently demonstrate by specific ELISA that the stable pentapeptide metabolite (1-5 BK) of BK increases from 2.5 ± 1.0 to 11.0 ± 2.5 pg/ml plasma (P<0.05) in elderly volunteers and from 2.0 ± 1.0 to 10.3 ± 3.2 pg/ml plasma (P<0.05) in young volunteers 3 h following food intake. This result suggests that ingestion of food stimulates BK release from kininogen in normal man. Postprandial splanchnic vasodilatation, demonstrated by a decrease of plasma half-life of intravenously administered indocyanine green (ICG), a marker of mesenteric blood flow to the liver, from 4.4 ± 0.4 to 3.0 ± 0.1 min (P<0.05) in young volunteers and from 5.2 ± 1.0 to 4.0 ± 0.5 min (P<0.05) in elderly volunteers, accompanied BK release. The participation of BK in this response was investigated in subjects given the BK-potentiating drug captopril prior to food intake. Postprandial decreases of ICG half-lives were not changed by this treatment in either young or elderly subjects, a result which may indicate that BK released following food intake plays no role in postprandial splanchnic vasodilatation in normal man.

Delay in gallbladder emptying during the perimenopausal period

A pilot study has ascribed an important role in gallbladder motility and emptying to the perimenopausal period. To assess the effect of this period on gallbladder emptying and cholelithogenesis, 25 women in the perimenopausal period without gallbladder disease were submitted to cholangiography and two ultrasound exams. The time for gallbladder emptying and the presence of cholelithiasis were assessed. All patients presented a delay in gallbladder emptying with no relationship to the pre- or postmenopausal period. This finding was not related to lithogenesis. Gallbladder emptying time is longer during the perimenopausal period.

Postprandial symptoms in dysmotility-like functional dyspepsia are not related to disturbances of gastric myoelectrical activity

Gastric dysrhythmias, such as tachy- or bradygastria, have been reported in patients with functional dyspepsia (FD), but their role in symptom production is uncertain. It is also not known whether gastric dysrhythmias in these patients can be elicited by physiological gastric distension with a meal. We investigated the relationships between symptoms after ingestion of different volumes of water following a test meal and gastric dysrhythmias in FD patients. Fourteen patients with dysmotility-like FD and 13 healthy volunteers underwent paired electrogastrography (EGG) studies. Fasted subjects ingested 150 ml of yoghurt with either 150 ml (low volume) or 300 ml (high volume) water in random order. Fasting and fed EGGs with monitoring of symptoms were performed in both studies. Ten FD patients (71.4%) reported upper abdominal discomfort and bloating after the low volume meal, but only one (7.1%) presented an abnormal EGG (dominant frequency in the 2-4-cpm range: 58%). Following the high volume meal, 7 patients (50%) had symptoms, but none had EGG abnormalities. No significant differences were found between FD patients and controls for any of the EGG variables, in any test. In FD patients with postprandial symptoms, the percentage of the EGG dominant frequency in the normal range (median, 84.6%; range, 76.0-100.0%) was similar (P > 0.20) to that in those without symptoms (88.5%; 75.0-100.0%). We conclude that disturbances of gastric myoelectrical activity are unlikely to play a role in the origin of postprandial upper abdominal discomfort and bloating in dysmotility-like FD.

The modest but growing Brazilian presence in psychiatric, psychobiological and mental health research: assessment of the 1998-2002 period

The objective of the present survey was to assess the Brazilian scientific production in psychiatry, psychobiology, and mental health during the 1998-2002 period. The universities' graduate programs concentrate the vast majority of the scientific production in Brazil. We assessed the annual reports from the graduate programs to the Brazilian Ministry of Education concerning master's and doctoral theses and the articles published in journals indexed by the Institute of Scientific Information (ISI). There are nine Master's and Doctoral graduate programs dedicated to research in psychiatry, neuropsychiatry, psychobiology, and mental health in the country, seven being located in southern states. During the 5-year period, from 1998 to 2002, 186 students received their doctorate degree (37/year). The programs published 637 articles in journals indexed by ISI, the majority of them in journals with an impact factor higher than 2. The research advisors' productivity varied among graduate programs, ranging from 0.6 to 2.0 articles per year in ISI-indexed journals. Despite the substantial barriers faced by the Brazilian scientific community (mainly financial and writing difficulties), Brazil's scientific mental health production is on the rise. The number of articles published in ISI-indexed journals has doubled without a significant increase in the number of graduate theses, suggesting that there was an improvement in both the quality of the scientific production and the productivity of the graduate programs. Based on these data, it is reasonable to predict a tendency to an increase in production over the next few years.

Implications of extubation failure and prolonged mechanical ventilation in the postoperative period following elective intracranial surgery

Patients undergoing neurosurgery are predisposed to a variety of complications related to mechanical ventilation (MV). There is an increased incidence of extubation failure, pneumonia, and prolonged MV among such patients. The aim of the present study was to assess the influence of extubation failure and prolonged MV on the following variables: postoperative pulmonary complications (PPC), mortality, reoperation, tracheostomy, and duration of postoperative hospitalization following elective intra-cranial surgery. The study involved a prospective observational cohort of 317 patients submitted to elective intracranial surgery for tumors, aneurysms and arteriovenous malformation. Preoperative assessment was performed and patients were followed up for the determination of extubation failure and prolonged MV (>48 h) until discharge from the hospital or death. The occurrence of PPC, incidence of death, the need for reoperation and tracheostomy, and the length of hospitalization were assessed during the postoperative period. Twenty-six patients (8.2%) experienced extubation failure and 30 (9.5%) needed prolonged MV after surgery. Multivariate analysis showed that extubation failure was significant for the occurrence of death (OR = 8.05 [1.88; 34.36]), PPC (OR = 11.18 [2.27; 55.02]) and tracheostomy (OR = 7.8 [1.12; 55.07]). Prolonged MV was significant only for the occurrence of PPC (OR = 4.87 [1.3; 18.18]). Elective intracranial surgery patients who experienced extubation failure or required prolonged MV had a higher incidence of PPC, reoperation and tracheostomy and required a longer period of time in the ICU. Level of consciousness and extubation failure were associated with death and PPC. Patients who required prolonged MV had a higher incidence of extubation failure.

Analysis of acylcarnitine profiles in umbilical cord blood and during the early neonatal period by electrospray ionization tandem mass spectrometry

Acylcarnitine profiling by electrospray ionization tandem mass spectrometry (ESI-MS/MS) is a potent tool for the diagnosis and screening of fatty acid oxidation and organic acid disorders. Few studies have analyzed free carnitine and acylcarnitines in dried blood spots (DBS) of umbilical cord blood (CB) and the postnatal changes in the concentrations of these analytes. We have investigated these metabolites in healthy exclusively breastfed neonates and examined possible effects of birth weight and gestational age. DBS of CB were collected from 162 adequate for gestational age neonates. Paired DBS of heel-prick blood were collected 4-8 days after birth from 106 of these neonates, the majority exclusively breastfed. Methanol extracts of DBS with deuterium-labeled internal standards were derivatized before analysis by ESI-MS/MS. Most of the analytes were measured using a full-scan method. The levels of the major long-chain acylcarnitines, palmitoylcarnitine, stearoylcarnitine, and oleoylcarnitine, increased by 27, 12, and 109%, respectively, in the first week of life. Free carnitine and acetylcarnitine had a modest increase: 8 and 11%, respectively. Propionylcarnitine presented a different behavior, decreasing 9% during the period. The correlations between birth weight or gestational age and the concentrations of the analytes in DBS were weak (r £ 0.20) or nonsignificant. Adaptation to breast milk as the sole source of nutrients can explain the increase of these metabolites along the early neonatal period. Acylcarnitine profiling in CB should have a role in the early detection of metabolic disorders in high-risk neonates.

Relationship between genetic mutation variations and acute-phase reactants in the attack-free period of children diagnosed with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a periodic autoinflammatory disease characterized by chronic inflammation. This study investigated the relationship between acute-phase reactants and gene mutations in attack-free periods of childhood FMF. Patients diagnosed with FMF were divided into four groups based on genetic features: no mutation, homozygous, heterozygous, and compound heterozygous. These groups were monitored for 2 years, and blood samples were collected every 6 months during attack-free periods. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and white blood cell count were measured. A disease severity score was determined for each patient. Mean values for erythrocyte sedimentation rate and fibrinogen were significantly different in the homozygous group. White blood cell count and C-reactive protein were similar between the groups. Disease severity score was higher in patients with the M694V mutation than in individuals without the mutation, as well as in those with other mutation groups. Periodic follow-up of patients with FMF MEFV mutations in subjects with acute-phase reactants may be useful in the prevention of morbidity.

Effect of holding period prior to storage on the chemical attributes of Starking Delicious apples during refrigerated storage

In this research, the effects of three different holding periods (6, 12 and 24 hours) prior to storage on the quality attributes of Starking Delicious apples were investigated during storage of 8 months at 0.5 ± 1.0 ºC. Changes in weight loss, flesh firmness, pH values, soluble dry matter amount, titratable acidity values, ascorbic acid contents, and total and reducing sugar content were determined. According to the results, the holding period showed statistically significant changes in the quality attributes of the apples (p < 0.05).

Characterization and effect of clarified araçá (Psidium guineenses Sw.) juice on postprandial glycemia in healthy subjects

Brazilian native fruits are excellent sources of bioactive compounds of phenolic nature. Some of these compounds are able to inhibit carbohydrate- metabolizing enzymes (in vitro), α-amylase and α-glucosidase, delaying carbohydrate digestion. This study aimed to evaluate the effect of clarified araçá (Psidium guineenses Sw.) juice on postprandial glycemia in humans after consumption of 25 g of available carbohydrates (approximately 50 g of white bread) and characterize the phenolic compounds and in vitro antioxidant capacity of araçá juice and pulp. The results showed that the clarified juice had a positive effect on postprandial glycemia reducing the total amount of glucose absorbed, lengthening the time to reach maximum blood glucose concentration, reducing glucose incremental velocity, and decreasing glucose incremental percentage. Both frozen pulp and clarified juice had high amounts of phenolic compounds, antioxidant capacity, and proanthocyanidins, among which oligomers (monomers to tetramers), pentamers, hexamers, heptamers, octamers, nonamers, decamers, and polymers were detected, and they are probably associated with in vivo effects.

Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation”) were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

Effect of storage period on isoflavone content and physiological quality of conventional and transgenic soybean seeds

The objective in this research was to evaluate the isoflavone content and the physiological quality of seed from conventional and transgenic soybean cultivars before and after 180 days of storage. Twenty one soybean cultivars: CD 202, CD 206, CD 208, CD 213RR, CD 214RR, CD 215, CD 216, CD 217, CD 218, CD 221, BRS 184, BRS 185, BRS 214, BRS 244RR, BRS 245RR, BRS 246RR, BRS 255, BRS 257, BRS 258, BRS 261 and BRS 262, grown in the 2005/2006 crop season, were assayed. The seeds were packed in Kraft paper bags and stored at room temperature under laboratory conditions. Seeds were evaluated with respect to their germination and vigor (first germination count, accelerated aging and tetrazolium test) and their total isoflavone contents and respective aglycon forms (daidzein, genistein and glycitein),glycosides (daidzine, genistine and glycitine) and malonyl conjugates. A completely randomized block design with six replications with the treatments set out within a subplot scheme (21 cultivars x 2 storage periods) was used. The F-test was used to compare means between storage periods and the Scott-Knott test to compare cultivars for each storage period, both with a 95% probability. It was concluded that isoflavone contents differ between cultivars and show a distinct behavior throughout storage.