Delayed riluzole treatment is able to rescue injured rat spinal motoneurons.

The effect of delayed 2-amino-6-trifluoromethoxy-benzothiazole (riluzole) treatment on injured motoneurons was studied. The L4 ventral root of adult rats was avulsed and reimplanted into the spinal cord. Immediately after the operation or with a delay of 5, 10, 14 or 16 days animals were treated with riluzole (n=5 in each group) while another four animals remained untreated. Three months after the operation the fluorescent dye Fast Blue was applied to the proximal end of the cut ventral ramus of the L4 spinal nerve to retrogradely label reinnervating neurons. Three days later the spinal cords were processed for counting the retrogradely labeled cells and choline acetyltransferase immunohistochemistry was performed to reveal the cholinergic cells in the spinal cords. In untreated animals there were 20.4+/-1.6 (+/-S.E.M.) retrogradely labeled neurons while in animals treated with riluzole immediately or 5 and 10 days after ventral root avulsion the number of labeled motoneurons ranged between 763+/-36 and 815+/-50 (S.E.M.). Riluzole treatment starting at 14 and 16 days after injury resulted in significantly lower number of reinnervating motoneurons (67+/-4 and 52+/-3 S.E.M., respectively). Thus, riluzole dramatically enhanced the survival and reinnervating capacity of injured motoneurons not only when treatment started immediately after injury but also in cases when riluzole treatment was delayed for up to 10 days. These results suggest that motoneurons destined to die after ventral root avulsion are programmed to survive for some time after injury and riluzole is able to rescue them during this period of time.

Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats.

Neuropathic alterations of sensory nerves involved in the mediation of neurogenic inflammation of the meninges may contribute to the increased incidence of headaches in diabetics. In the rat, activation of capsaicin-sensitive nociceptors, which express the transient receptor potential vanilloid type 1 (TRPV1) receptor, induces meningeal vasodilatation, a significant component of neurogenic inflammation, through the release of calcitonin gene-related peptide (CGRP). This study examines the effects of streptozotocin-induced diabetes on TRPV1 receptor-mediated neurogenic sensory vasodilatation, CGRP release and nerve fiber density in the rat dura mater. In a cranial window preparation, epidural application of capsaicin (10(-7) M) produced distinct vasodilatory responses in control animals as measured by laser Doppler flowmetry. In diabetic rats, capsaicin-induced vasodilatation was reduced or even abolished 6, but not 2 or 4 weeks after diabetes induction. In contrast, vasoconstriction, a non-neurogenic response to capsaicin at a higher concentration (10(-5) M), was not altered in diabetic rats. The vasodilatory effects of histamine (10(-5) M), acetylcholine (10(-4) M) and CGRP (10(-5) M) were similar in control, diabetic and insulin-treated diabetic animals. In diabetic rats, a significant decrease in the capsaicin-evoked release of CGRP and reduction in the density of TRPV1-immunoreactive (IR) nerves were demonstrated. Treatment of the diabetic rats with insulin restored both the vasodilatory response and the capsaicin-induced CGRP release toward control values. In conclusion, this study revealed a marked impairment of meningeal TRPV1-IR nerves in streptozotocin diabetic rats by showing reduced neurogenic sensory vasodilatation, decreased capsaicin-evoked CGRP release and reduction in the number of TRPV1-IR nerve fibers of the dura mater. The findings suggest that capsaicin-sensitive afferents may play an important role in meningeal nociceptor function and their dysfunction, e.g. due to a limited removal of inflammatory mediators and/or tissue metabolites from the meningeal tissue, may contribute to the enhanced incidence of headaches in diabetics.

The effects of pentobarbitone and pethidine on foetal breathing movements in sheep.

1 Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age. 2 In contrast, relatively large doses of pethidine (100-200 mg) admininstered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia. 3 The results are discussed in relation to feotal sleep state.

Nonenzymatic antioxidants of blood in multiple sclerosis.

Free radical action has been suggested as a causal factor in multiple sclerosis. We investigated the plasma level of lipid peroxides expressed in terms of malone dialdehyde and changes in blood nonenzymatic antioxidants (glutathione, alpha-tocopherol, retinol, plasma sulfhydryl groups, and uric acid) in multiple sclerosis patients with exacerbation or in remission, including a group treated with beta-interferon. The malone dialdehyde level was increased by 38% (n.s.) during exacerbations. The blood concentration of oxidized glutathione was likewise elevated (P<0.05), while the ratio of plasma alpha-tocopherol to cholesterol plus triglyceride was decreased (P<0.001). These changes suggest increased free radical production and consumption of the scavenger molecules during the active phase of the disease. Blood reduced glutathione level was increased (P<0.01) during exacerbation and remission as well. The rise in this thiol is likely to be a compensatory mechanism defending the cells from further oxidant injuries. Beta-interferon increased plasma alpha-tocopherol levels (P<0.001) but not the lipid corrected alpha-tocopherol value. Other parameters were not influenced by the drug.

Phacoemulsification in eyes with past pars plana vitrectomy: case-control study.

PURPOSE: To determine intraoperative and postoperative complications and outcomes of phacoemulsification of cataract in eyes that had previous pars plana vitrectomy. SETTING: University-based anterior segment disease referral practice. METHODS: This was a retrospective case-control study of a surgical series of 52 consecutive postvitrectomy cataract extractions statistically compared with control eyes from the same practice. RESULTS: Cataract extraction followed vitrectomy by 2 months to 6 years (mean 19 months). Cataracts with a posterior subcapsular component were seen more frequently in postvitrectomy eyes (58% versus 25% in control eyes). Cataract extraction after pars plana vitrectomy was often more challenging than in control eyes. Challenges included unstable posterior capsules, loose zonules, and posterior capsule plaque. Postoperative posterior capsule opacification (PCO) was more common in study than in control eyes (51% versus 21%; P = .002), especially if expandable gas or silicone oil had been used at vitrectomy. Visual acuity improved in 87% of study eyes, with 46% achieving a visual acuity of 20/40 or better. In study eyes in which the indication for vitrectomy was macular hole or epiretinal membrane, nuclear sclerosis was the most common cataract type, no intraoperative complications occurred, the PCO rate was low (13%), and visual acuity was better (73% 20/40 or better) than in the other study eyes. CONCLUSION: Phacoemulsification after pars plana vitrectomy can be performed with a low complication rate and with good visual results, although limited by underlying retinal disease. Posterior capsule opacification requiring neodymium: YAG capsulotomy was common in this series.

Differential regulation of vasopressin gene expression in the hypothalamus of endotoxin-treated 14-day-old rat.

The E. coli endotoxin 0111 B4, a lipopolysaccharide (LPS), in a dose of 200 ng/kg body weight/50 microl artificial cerebrospinal fluid (CSF) was given intracisternally to 14-day-old rats. Four hours later CSF, blood and urine were sampled, and consecutive brain sections from the hypothalamic area of the brain were prepared for in situ hybridization. The LPS treatment resulted in a significant (p<0.001) pleocytosis and an elevation of the protein content of the CSF. There were no changes observed in the chemical parameters of the CSF, plasma, blood or urine, i.e. vasopressin (VP) levels, osmolality, Na+ and K+ concentrations, glucose level, pH, bicarbonate or PaCO2, PaO2 values. LPS injection, however, resulted in a significantly (p<0.01) increased VP mRNA level (121% of the control value) in the supraoptic nuclei (SON), but not in the paraventricular nuclei (PVN), as compared to controls. Our findings suggest an early effect of LPS on VP gene expression selectively in the SON of 14-days-old rats. This animal model might be suitable for studying the regulation of VP gene expression and the role of this peptide in the pathogenesis of bacterial meningitis in pediatric patients.

Removal of electrolytes from institutionally packaged foods.

Soaking and rinsing resulted in significant (p less than .01) reductions in sodium and potassium concentrations of peeled potatoes and hard-cooked eggs packed in brines containing sodium compounds and packaged for institutional use. In this study, no significant differences (p greater than .01) were found between soaking and rinsing in deionized water and in tap water; however, tap water can vary greatly in sodium and potassium content. Sodium and potassium levels of chopped lettuce dipped in sodium hypochlorite were not significantly (p greater than .01) affected by soaking and rinsing procedures. However, the sodium and potassium levels of the processed lettuce were not high relative to the levels of unprocessed lettuce before soaking and rinsing.

Inhibitory effects of methylxanthines on the pre-eclamptic-like symptoms in ewes.

OBJECTIVE: Our objective was to determine whether two methylxanthines, pentoxifylline (PTX) and allopurinol, would have beneficial effects on experimental pregnancy-induced pre-eclampsia- like disease in ewes. STUDY DESIGN: 20 animals at the gestational age of 130-135 days were divided into four groups (control; fasting; fasting, pentoxifylline-treated; and fasting, allopurinol-treated). The illness was provoked with a 4-day fasting period. Electrolytes, glucose, conventional parameters, plasma haem content, indirect bilirubin concentration and free thiol levels were measured. RESULTS: Unlike in the fasting group, conventional signs of the disease, such as hypertension, kidney and liver injury and platelet count decrease, were all mitigated in the fasting, drug-treated animals. In the treated animals plasma haem content increased by a less significant level, while indirect bilirubin concentration showed a more rapid rise. CONCLUSIONS: Both methylxanthines partly inhibited the pre-eclamptic-like symptoms in ewes. We speculate that the better induction of haem oxygenase might play an important role in this inhibitory effect on this particular animal model.

Improving reproductive performance in lactating dairy cows by synchronizing ovulation or inducing oestrus.

Lactating crossbred Holstein-Friesian dairy cows (n = 331) were started on an Ovsynch regimen 68 +/- 8.2 days after calving; 200 micrograms GnRH intramuscularly (i.m.) on Days 0 and 9, and 35 mg prostaglandin F2 alpha i.m. on Day 7. Thirty-eight and 31 cows (11.5 and 9.4%, respectively) were in oestrus on Days 0 to 6 and 7 to 8, respectively, and inseminated, and the remainder were fixed-time inseminated (on Day 10). For these three groups, pregnancy rates (60-65 days after breeding) were 31.6, 38.7 and 34.0%, respectively (P = 0.82) and calving rates were 100, 100 and 89.9% (P = 0.23). In a preliminary trial, twelve lactating cows (45 to 60 days postpartum) with inactive ovaries were given 1500 IU eCG i.m.; 10 were in oestrus within 10 days after treatment (and inseminated) and eight of these were pregnant (30 days after breeding). The Ovsynch program resulted in acceptable reproductive performance in cyclic cows and eCG treatment has considerable promise for inducing oestrus in anoestrous cows.

[Possible pitfalls in giving expert opinion in legal actions against medical services]. / Szakmai tévedések lehetösége orvosi perek szakértöi véleményezésében.

The authors report their experience in cases under legal action against medical service needing expert opinion. By the rapid development and differentiation of medical science in the recent years the possibility of making mistake in every day practice increased, on the other hand this circumstance includes also occurrence of the pitfalls in giving expert opinion in legal actions against medical service.

[Resuscitation of neonates in the delivery room. Recommendations by the American Heart Association and American Academy of Pediatrics]. / Ujszülöttek szülöszobai resuscitatiója.

According to the recommendation of the American Heart Association and the American Academy of Pediatrics 43 newborn babies with mean birth weight 3300 g (range 610-5100 g) were resuscitated. One-minute Apgar score was 0:1, 1:22, 2:11, 3:7, 4:2 cases. Mask and bag ventilation were needed in 43, heart compression in 7, tracheal intubation in 2, drugs in 2 cases. Five-minute Apgar values were 8:39, 5:1, 7:1 case. All resuscitations were successful. The resuscitation program is a great advance in the field of neonatology. Nationwide application of it might be helpful to decrease neonatal mortality in Hungary.

[Reoxigenation after neonatal asphyxia with 21% or 100% oxygen in piglets]. / Ujszülöttkori asphyxiát követö reoxigenizáció sertéseken 21% vagy 100% oxigénnel.

Birth asphyxia represents a serious problem worldwide, resulting in 1 million deaths and an equal number of neurologic sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. In the present study we tested the effect of reoxygenation with room air or 100% oxygen following experimental pneumothorax induced asphyxia on blood oxidative stress indicators, early neurologic outcome and cerebral histopathology of newborn piglets. 26 animals were studied in three experimental groups: sham-operated (SHAM, n = 6), reoxygenation with room air after pneumothorax (RORA, n = 10) and reoxygenation with 100% oxygen after pneumothorax (RO100, n = 10). In RORA and RO100 asphyxia was induced under anesthesia with bilateral intrapleural room air insufflation. Gasping, bradyarrhythmia, arterial hypotension, hypoxemia, hypercarbia and severe combined acidosis occurred 62 +/- 6 (RORA) and 65 +/- 7 min (RO100) after the start of the experiments, when the pneumothorax was relieved and ten min of reoxygenation period was started with mechanical ventilation with room air (RORA) or 100% oxygen (RO100). Then the spontaneously breathing animals were followed on room air during the next three hours. Blood oxidative stress indicators--as oxidized and reduced glutathione, plasma hemoglobin and malondialdehyde concentrations--were also measured at different stages of the experiments and early neurologic examinations (neurological score: 20 = normal, 5 = brain dead) were performed at the end of the study. Then the brains were fixed and stained. In SHAM blood gases and acid/base status differed significantly from values measured in RORA and RO100. In RO100 PaO2 was significantly higher at 5 (13.8 +/- 1.8 kPa) and 10 min (13.2 +/- 2.0 kPa) than in RORA (8.7 +/- 0.9, 9.2 +/- 1.0 kPa), respectively. All the measures of oxidative stress indicators remained unchanged in the study groups (SHAM, RORA, RO100). Neurologic examination scores from SHAM were 18 +/- 0, from RORA 13.5 +/- 1.0 and from RO100 9.5 +/- 1.3 (significant differences between SHAM and RORA and RO100, significant difference between RORA and RO100). Cerebral histopathology showed marked damage with similar severity in both asphyxiated groups. We conclude that blood oxidative stress indicators and cerebral histopathology did not differ significantly after 10 min reoxygenation either with room air or with 100% oxygen following pneumothorax induced asphyxia, but reoxygenation with 100% oxygen might impair the early neurologic outcome of newborn pigs.

Surface tension, glutathione content and redox ratio of the tracheal aspirate fluid of premature infants with IRDS.

OBJECTIVE: Determination of the surface tension (ST), the total glutathione (GL) content and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) in the tracheal aspirate (TA) of newborn infants with IRDS. METHODS: The ST of the TA was determined by monitoring the fluid level pulsated in a capillary glass tube by means of a digitalized videocomputerized picture analysis program, a technique developed in our laboratory. The concentrations of GSSG and total GL in the TA were determined enzymatically with glutathione reductase. All results of laboratory tests were referred to the total phospholipid (PL) concentration. Patients, Experimental Material: TA samples were collected from 32 intubated premature and newborn infants admitted to the NICU with IRDS during the first 2 weeks of their lives. Control samples were obtained from 11 children prior to elective surgery. RESULTS: The ST relative to the PL content (surface tension index, STI) was significantly lower in the newborns with IRDS than in the control group, and the concentration of GSH in the TA was also markedly decreased in all IRDS infants studied. The concentration of GSSG and the ratio of GSSG to GSH were significantly higher in the severe cases and in those with an unfavourable prognosis. Surfactant treatment had a protective effect against oxidative stress, it induced a decrease in both the GSSG concentration and in the GL redox ratio (GSSG/GSH) in the TA. There was a close correlation between the GSH content and the STI value of the samples studied. CONCLUSION: Oxidation and consequent depletion of GSH in the TA may be an aggravating factor in the development of the insufficient surface activity in intubated newborns with IRDS.