Amniotic fluid lactic acid and matrix metalloproteinase-8 levels at the time of fetal surgery for a spine defect: association with subsequent preterm prelabour rupture of membranes.

OBJECTIVE: In utero fetal surgery to correct incomplete closure of the spinal cord lessens the extent of permanent damage but is associated with preterm prelabour rupture of membranes (PPROM). We determined whether compounds in amniotic fluid collected at the time of surgery predicted subsequent development of PPROM. DESIGN: Prospective study. SETTING: Hospitals in Sao Paulo, Brazil. POPULATION: Twenty-four consecutive pregnant women at 24-26 weeks of gestation seen between February and October 2017 with a singleton pregnancy underwent in utero surgery to correct an open spinal defect in their fetus. METHODS: Amniotic fluid was tested for lactic acid, matrix metalloproteinase 2 (MMP-2), MMP-8, MMP-9 and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. Clinical data were collected after completion of all laboratory studies. MAIN OUTCOME MEASURE: Amniotic fluid concentration of compounds in women with or without PPROM. RESULTS: Preterm prelabour rupture of membranes occurred in seven (29.2%) women. There were no differences in maternal age, gravidity, parity, race, history of caesarean sections or fetal gender between women with or without PPROM. Length of surgery, days of wound healing and length of hospital stay were also indistinguishable. The median concentrations of MMP-8 (1.7 versus 0.6 ng/ml; P = 0.0041) and lactic acid (7.1 versus 5.9 mm; P = 0.0181) were higher in women with PPROM. The amniotic fluid MMP-8 level was also negatively correlated with gestational age at delivery (Spearman r = -0.4217, P = 0.0319). CONCLUSION: Differences in susceptibility to develop PPROM are present before fetal surgery. An increase in anaerobic glycolysis, evidenced by the intra-amniotic lactic acid level, may enhance MMP-8 production and weaken maternal and fetal membranes. TWEETABLE ABSTRACT: Matrix metalloproteinase-8 and lactic acid in amniotic fluid predict preterm prelabour rupture of membranes.

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

UNLABELLED: Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. CONCLUSIONS: (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers.

Eag1, Eag2, and SK3 potassium channel expression in the rat hippocampus after global transient brain ischemia.

Transient global brain ischemia causes delayed neuronal death in the hippocampus that has been associated with impairments in hippocampus-dependent brain function, such as mood, learning, and memory. We investigated the expression of voltage-dependent Kcnh1 and Kcnh5, ether à go-go-related Eag1 and Eag2 (K(V) 10.1 and K(V) 10.2), and small-conductance calcium-activated SK3 (K(Ca) 2.3, Kcnn3) K(+) channels in the hippocampus in rats after transient global brain ischemia. We tested whether the expression of these channels is associated with behavioral changes by evaluating the animals in the elevated plus maze and step-down inhibitory avoidance task. Seven or tweny-eight days after transient global brain ischemia, one group of rats had the hippocampus bilaterally dissected, and mRNA levels were determined. Seven days after transient global brain ischemia, the rats exhibited a decrease in anxiety-like behavior and memory impairments. An increase in anxiety levels was detected 28 days after ischemia. Eag2 mRNA downregulation was observed in the hippocampus 7 days after transient global brain ischemia, whereas Eag1 and SK3 mRNA expression remained unaltered. This is the first experimental evidence that transient global brain ischemia temporarily alters Eag2. The number of intact-appearing pyramidal neurons was substantially decreased in CA1 and statistically measurable in CA2, CA3, and CA4 hippocampal subfields compared with sham control animals 7 or 28 days after ischemia. mRNA expression in the rat hippocampus. The present results provide further information for the characterization of the physiological role of Eag2 channels in the central nervous system.

Molar pregnancy and husband's occupation: do soil and dust have any role?

This case-control study investigated the association between molar pregnancy and husband's work. In the analysis, cases were 30 women with complete mole and controls were 30 matched women with term pregnancies. The husband's of cases were more likely to have occupations involving physical work than non-physical work and this physical work more usually involved exposure to soil and dust. Among all occupations, the husband's of cases were more likely to have occupations which had exposure to soil and dust (P < 0.01). Comparing all occupations that had exposure to soil and dust with all those who did not have this exposure (physical and non-physical) resulted in a statistically significant difference in the occurrence of molar pregnancy (P < 0.001).

Molar pregnancy and husband's occupation: do soil and dust have any role?

This case-control study investigated the association between molar pregnancy and husband's work. In the analysis, cases were 30 women with complete mole and controls were 30 matched women with term pregnancies. The husbands of cases were more likely to have occupations involving physical work than non-physical work and this physical work more usually involved exposure to soil and dust. Among all occupations, the husbands of cases were more likely to have occupations which had exposure to soil and dust [P < 0.01]. Comparing all occupations that had exposure to soil and dust with all those who did not have this exposure [physical and non-physical] resulted in a statistically significant difference in the occurrence of molar pregnancy [P < 0.001]

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain.

A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0 masculine C until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm(3)), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm(3), also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain

A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10 percent formalin at 0ºC until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm ), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent ( percent) of the affected (left) hemisphere, correlated closely with volume (mm , also reported as percent) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

Tacrolimus (FK506) reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study.

The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv) immediately after ischemia. In the second series, FK506 (1.0 mg/kg) was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip) 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001). FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1), and after five iv injections of 1.0 mg/kg (experiment 3). In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01). Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05); however, this effect did not alter normothermia (37 C). FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage.

Tacrolimus (FK506) reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study

The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv) immediately after ischemia. In the second series, FK506 (1.0 mg/kg) was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip) 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001). FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1), and after five iv injections of 1.0 mg/kg (experiment 3). In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01). Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05); however, this effect did not alter normothermia (37ºC). FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage

Trombosis venosa cerebral secundaria a síndrome antifosfolípido y déficit de antitrombina III / Cerebral venous thrombosis secondary to antiphospholipid syndrome and dificit of antithrombin III

La trombosis venosa cerebral es menos frecuente que la arterial como causa de stroke, sin embargo aún continua subdiagnosticada. Fisiopatológicamente se caracteriza por un desequilibrio entre factores trombogénicos y fibrinolíticos. Los desórdenes hematológicos tienen un rol protagónico importante, destacándose entre ellos el sindrome antifosfolipídico, el cual debe particularmente sospecharse cuando el accidente cerebrovascular ocurre en individuos jóvenes

Trombosis venosa cerebral secundaria a síndrome antifosfolípido y déficit de antitrombina III / Cerebral venous thrombosis secondary to antiphospholipid syndrome and dificit of antithrombin III

La trombosis venosa cerebral es menos frecuente que la arterial como causa de stroke, sin embargo aún continua subdiagnosticada. Fisiopatológicamente se caracteriza por un desequilibrio entre factores trombogénicos y fibrinolíticos. Los desórdenes hematológicos tienen un rol protagónico importante, destacándose entre ellos el sindrome antifosfolipídico, el cual debe particularmente sospecharse cuando el accidente cerebrovascular ocurre en individuos jóvenes (AU)

Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia.

In the central nervous system, magnesium ion (Mg2+) acts as an endogenous modulator of N-methyl-D-aspartate (NMDA)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34), DZ (10 mg/kg, N = 24), MgCl2 (2.5 mmol/kg, N = 10), MgCl2 (5.0 mmol/kg, N = 17), MgCl2 (7.5 mmol/kg, N = 9) or MgCl2 (5 mmol/kg) + DZ (10 mg/kg, N = 14). Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3%) and CA1 (88.4%) sectors of the hippocampus (P<0.0001, vehicle vs sham). Compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86. 7-93.4%) and CA1 (lesion: 85.5-91.2%) pyramidal cells (P>0.05). Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05). No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.

Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

In the central nervous system, magnesium ion (Mg2+) acts as an endogenous modulator of N-methyl-D-aspartate (NMDA)-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg), either alone or in combination with diazepam (DZ), on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g) were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc) in single (1x, 2 h post-ischemia) or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia). DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34), DZ (10 mg/kg, N = 24), MgCl2 (2.5 mmol/kg, N = 10), MgCl2 (5.0 mmol/kg, N = 17), MgCl2 (7.5 mmol/kg, N = 9) or MgCl2 (5 mmol/kg) + DZ (10 mg/kg, N = 14). Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3 percent) and CA1 (88.4 percent) sectors of the hippocampus, vehicle vs sham). Compared to the vehicle-treated group, all pharmacological treatments failed to attenuate the ischemia-induced death of both subiculum (lesion: 86.7-93.4 percent) and CA1 (lesion: 85.5-91.2 percent) pyramidal cells. Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly. No animaldeath was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats

Loss of CA1 cells following global ischaemia correlates with spatial deficits in the circular platform task.

The effect of 15 min, four-vessel-occlusion (4-VO) ischaemia on performance by rats in the circular platform task (CPT) was investigated. Possible correlations between the extent of hippocampal cell loss and behavioural disruption were evaluated. Sham-operated controls (n=10) and 4-VO ischaemic animals (n=32) were required to escape from a 1.2 m diameter, brightly illuminated, white surface into a dark goal box located under one of 18 equally-spaced, 9 cm diameter holes arranged around the circumference (3 trials per day). The goal box was maintained in a single, fixed, rewarded location relative to the extramaze cues for 7 days (days 16-22 post-ischaemia). During the reversal test, the goal box was transferred to a new location 140 degrees from the initial point and kept in this new position from day 23 through day 25 post-ischaemia. Ischaemic rats were slower to find the goal box than sham-operated controls; this learning deficit correlated with the degree of neuronal loss in the CA1, but not in the CA2, CA3 and CA4 subfields and presubiculum of the hippocampal formation. During the reversal test, ischaemic rats persisted in searching for the goal box at the initially rewarded location. The circular platform task provides a good model for behavioural studies following transient forebrain ischaemia in the rat.

Interaction between recovery from behavioral asymmetries induced by hemivibrissotomy in the rat and the effects of apomorphine and amphetamine.

Spontaneous and drug-induced turning behavior and thigmotactic scanning were tested either acutely (4-6 hr) or chronically (9 days) after unilateral removal of vibrissae in rats. Rats that were tested acutely scanned more with the intact vibrissae side. This asymmetry was reduced in rats that were tested chronically, indicating behavioral recovery. The indirect dopamine agonist amphetamine induced a reversed asymmetry after 9 days because the animals then scanned more with the side lacking the vibrissae. Postsynaptic doses of apomorphine administered to acutely tested rats induced more scanning with, and more turning toward, the intact vibrissae side. A negative correlation was found in the chronically tested rats between the asymmetry in spontaneous scanning and the asymmetry after apomorphine. Nonrecovered rats showed indications of a reversal after apomorphine. The results are discussed in relation to mechanisms of neural plasticity in the basal ganglia, such as receptor supersensitivity and changes in nigrostriatal afferents.

Analysis of recovery from behavioral asymmetries induced by unilateral removal of vibrissae in the rat.

Unilateral removal of vibrissae in rats induces an asymmetry in the side of the face used to scan the wall while traversing the edge of an open field (thigmotactic scanning). This behavioral asymmetry recovers over time. The time course of asymmetry and recovery was systematically analyzed by testing groups of rats deprived of vibrissae for different periods of time. The preferential use of the hemiface with intact vibrissae persisted up to 3 days after vibrissae removal. It was expressed maximally during the first minute of testing. This phase was followed by a rapid return to symmetry by Day 6. Recovery to symmetry involved both a decrease in duration of scanning with the vibrissae-intact side and an increase with the vibrissae-clipped side of the face, with the total duration remaining constant throughout the states of asymmetry and recovery. The time course of behavioral recovery corresponds to the time course of neural plasticity in the basal ganglia that accompanies hemivibrissotomy, a result suggesting a functional link between the two phenomena.

[Treatment of neurological forms of Argentinian hemorrhagic fever with cytarabine]. / Traitement des formes nerveuses de la fièvre hémorragique argentine par la cytarabine.

The effects of cytarabine on neurological forms of Argentina Hemorrhagic Fever were evaluated in 125 patients. The mortality was 12.88 per cent compared to 61.40 per cent in untreated patients. (p less than 0.0001). The efficiency of this treatment depends on its early application. No side effect was observed.