Characterisation of rat superficial superior colliculus neurones: firing properties and sensitivity to GABA

Physiological, pharmacological and morphological properties of superficial superior colliculus neurones (n=93) were characterised using whole-cell patch-clamp recordings in rat brain slices. Six cell types (narrow- and wide-field vertical, horizontal, piriform, marginal and stellate) were identified based on Lucifer Yellow labelling but no cell type-specific spike pattern could be identified. Resting membrane potentials were homogeneous (mean: -67.1 +/- 0.7 mV, n=48), and spike frequencies ranged from 10 to 70 Hz (80 pA current injection). About 66% of the cells displayed regular and sustained spike production, throughout all neuronal categories. Rebound spikes and spontaneous activity were observed frequently in all cell types. Synaptically evoked action potentials appeared as single spikes (mean amplitude: 76.0 +/- 3.2 mV, n=34) followed by a fast after-hyperpolarising potential (mean amplitude: 25.4 +/- 1.4 mV, n=34) and variable late potentials (late after-depolarising and/or -hyperpolarising). Pharmacologically, a characterisation using GABA and its subtype-specific agonists indicated a strong inhibitory influence of this transmitter system on >90% of cells. The GABA(A) receptor agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (100 microM), caused a reversible hyperpolarisation (approximately 9 mV) and spike inhibition of all neurones studied. This was more pronounced for intrinsic than for synaptically evoked spikes. Assessment of the GABA(C) receptor agonist, cis-4-aminocrotonic acid (1 mM), also revealed a hyperpolarisation (approximately 3 mV) and an inhibitory action on firing, but this was not as potent and homogeneous, compared to the GABA(A) receptor agonist. Further, the GABA(B) receptor agonist, baclofen (50-100 microM), had more variable (hyperpolarising, depolarising or no change) effects on the membrane potential. It showed little modulation of current-induced action potentials but fully blocked synaptic spikes. Assessment of GABA receptor antagonist actions revealed the presence of weak tonic and strong phasic GABA(A) receptor-mediated inhibition in the superficial superior colliculus: application of the GABA(A) receptor antagonist, bicuculline (100 microM), led to a generally enhanced excitability and depolarisation (approximately 5 mV). Intrinsic firing was somewhat enhanced, but synaptic spiking was drastically potentiated and prolonged. In contrast, 1,2,5,6-tetrahydro-(pyridin-4-yl) methylphosphinic acid (TPMPA; 100 microM), the GABA(C) receptor antagonist, produced little effect on these physiological parameters. The GABA(B) receptor antagonist, CGP35348 (200 microM), caused a partial inhibition of late after-hyperpolarising potentials (approximately 30%). Uptake of GABA contributes little to endogenous inhibition in the superior colliculus slice preparation, as suggested by the action of GABA uptake inhibitors SKF89976 (50-100 microM) and nipecotic acid (200-500 microM), both had no obvious effect on physiological parameters. However, in the presence of these compounds, sub-maximal inhibitory actions of GABA were potentiated.In conclusion, different cell types in the superficial superior colliculus do not display distinct physiological properties and are subject to strong inhibitory modulation. We therefore suggest that signal processing in this brain region does not require cell type-specific encoding of information. In line with evidence provided by previous in vivo investigations, identification of visual stimuli and orientation responses appears to be realised via the network properties of the receptive fields that form topographic maps.     

The incidence of preterm deliveries decreases in Finland

Objective  We examined the trends and risk factors of preterm delivery.
Design  Register-based retrospective cohort study from Finland.
Setting  National Medical Birth Register data during 1987–2005.
Population  The study population consisted of 1 137 515 deliveries, of which 59 025 were preterm (5.2%).
Methods  We calculated the population attributable risks for using the risk factor prevalence rates in the population. We further calculated odds ratios with 95% CI by multivariate logistic regression to adjust for confounders.
Main outcome measures  Preterm delivery rate subclassified into moderately preterm (32–36 weeks), very preterm (28–31 weeks) and extremely preterm (less than 28 weeks).
Results  Preterm delivery rates increased from 5.1% in the late 1980s to 5.4% in the late 1990s but then decreased to 5.2% for 2001–05. The proportion of extremely preterm deliveries decreased substantially by 12% ( P < 0.01). The greatest risk factors were multiplicity (OR 13.72, 95% CI 13.26–14.19), followed by elective delivery (OR 1.86, 95% CI 1.82–1.89), primiparity (OR 1.47, 95% CI 1.45–1.50), in vitro fertilisation treatment (OR 1.39, 95% CI 1.31–1.47), maternal smoking (OR 1.31, 95% CI 1.29–1.34) and advanced maternal age (OR 1.02, 95% CI 1.02–1.03 for each additional year of age). Prematurity rates decreased by 1.8% after adjusting for risk variables.
Conclusions  The rate of preterm delivery has not increased from 1987 to 2005 in Finland, while the risk for extremely preterm delivery has decreased. This finding is in contrast with recent trends in other countries.     

Ketorolac is not nephrotoxic in connection with sevoflurane anesthesia in patients undergoing breast surgery

Ketorolac, which may cause renal vasoconstriction by cyclooxygenase inhibition, is often administered to patients anesthetized with sevoflurane that is metabolized to inorganic fluoride (F(-)), another potential nephrotoxin. We assessed this possible interaction using urine N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine (U-NAG/crea) as a marker of proximal tubular, beta2-microglobulin as a tubular, urine oxygen tension (P(u)O(2)) as a medullary, and erythropoietin as a marker of tubulointerstitial damage. Thirty women (ASA physical status I-II) undergoing breast surgery were included in our double-blinded study. They were allocated into two groups receiving either ketorolac 30 mg IM (Group K) or saline (Group C) at the time of premedication, at the end of, and 6 h after anesthesia maintained with sevoflurane. Urine output, U-NAG/crea, P(u)O(2,) serum creatinine, urea, and F(-) were assessed. Blood loss was larger in Group K (465 +/- 286 mL vs 240 +/- 149 mL, mean +/- SD, P < 0.05). The MAC-doses of sevoflurane were similar. U-NAG/crea increased during the first 2 h of anesthesia and serum F(-) peaked 2 h after the anesthesia without differences between the groups. There were no statistically significant changes in P(u)O(2), erythropoietin, beta2-microglobulin, serum creatinine, urea, or urine output during anesthesia or the recovery period in either group. Our results indicate that the kidneys are not affected by ketorolac administered in connection with sevoflurane anesthesia. IMPLICATIONS: The different kinetics of N-acetyl-beta-D-glucosaminidase indexed to urinary creatinine and serum inorganic fluoride during and after sevoflurane anesthesia suggest that the observed mild renal tubular function deterioration is not caused by inorganic fluoride. Administration of ketorolac IM is therefore considered safe in adequately hydrated healthy adult patients given sevoflurane anesthesia.     

Adverse trends in male reproductive health: we may have reached a crucial 'tipping point'

Healthy men produce an enormous number of sperms, far more than necessary for conception. However, several studies suggest that semen samples where the concentration of sperms is below 40 mill/mL may be associated with longer time to pregnancy or even subfertility, and specimens where the concentration of sperms is below 15 mill/mL may carry a high risk of infertility. Historic data from the 1940s show that the bulk of young men at that time had sperm counts far above 40 mill/mL with averages higher than 100 mill/mL. However, recent surveillance studies of young men from the general populations of young men in Northern Europe show that semen quality is much poorer. In Denmark approximately 40 percent of the men have now sperm counts below 40 mill/mL. A simulation assuming that average sperm count had declined from 100 mill/mL in 'old times' to a current level close to 40 mill/mL indicated that the first decline in average sperm number of 20-40 mill/mL might not have had much effect on pregnancy rates, as the majority of men would still have had counts far above the threshold value. However, due to the assumed decline in semen quality, the sperm counts of the majority of 20 year old European men are now so low that we may be close to the crucial tipping point of 40 mill/mL spermatozoa. Consequently, we must face the possibility of more infertile couples and lower fertility rates in the future.     

CAG repeat length in androgen receptor gene and male infertility in Egyptian patients

The CAG repeat and its association with infertility has been debatable. Therefore, this study was planned to assess the distribution of CAG repeat expansion in Egyptian patients and to investigate its association with male infertility. Forty-five infertile men were eligible for the study in addition to 20 aged-matched fertile males as control. Semen analysis, scrotal sonography, assay of serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and determination of the CAG repeat number within exon 1 of the androgen receptor (AR) gene were carried out. Statistically significant difference was found between infertile and control groups regarding sperm count, sperm motility, serum FSH level and CAG repeats (P < 0.05); statistically insignificant difference for the CAG repeats (P = 1.0) was found between oligozoospermic and asthenospermic groups; negative correlation was found between CAG repeat length and sperm count, and a positive correlation was found between CAG repeat length and serum FSH (P < 0.05). Our results validate the concept that long stretches of CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men.     

Increased incidence of Hirschsprung's disease in patients with hypoplastic left heart syndrome—a common neural crest-derived etiology?

Background

The enteric ganglions and the outflow tract of the heart originate from the neural crest. Impaired migration or differentiation of the neural crest cells causes Hirschsprung's disease (HD) and results in the development of cardiac outflow tract malformations. We hypothesize that the incidence of HD and bowel disorders associated with HD are increased in patients with hypoplastic left heart syndrome (HLHS) including left cardiac outflow tract obstruction.

Methods

All consecutive patients treated for HLHS at our institution during 1969 to 2005 were retrospectively reviewed. The number of patients with histologically confirmed HD or clinical findings characteristic of HD such as constipation and delayed meconium were recorded from the patient records.

Results

A total of 113 patients (65 males) were identified. At the time of survey, 57 patients (51%) were alive. Overall, there were 26 (23%) patients with constipation, and 9/23 (39%) had delayed passage of meconium after 48 hours. Despite frequent bowel disorders only 4 (3.5%) patients had undergone histologic examination of the rectum. Hirschsprung's disease was detected in 3 patients (95% confidence interval, 0.62-8.77). The expected number of HD cases in the study population was 0.026 giving 117-fold significant increase in the incidence of HD among patients with HLHS when compared to general Finnish population.

Conclusions

The incidence of HD is increased in patients with HLHS. These results point to a common neural crest-derived embryologic origin of HD and HLHS and warrant further studies.     

Value of albumin dialysis therapy in severe liver insufficiency

A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patients own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.     

Bone structure and volumetric density in young adults born prematurely: a peripheral quantitative computed tomography study

Prematurity is known to be associated with reduced bone mineral density (BMD) in childhood, but whether this condition has long-term detrimental consequences on adult bone structure is not known. In this study, we measured with peripheral quantitative computed tomography (pQCT) the total bone cross-sectional area, cortical area and wall thickness, cortical and trabecular density, and a density-weighed polar section modulus as a bone strength index (BSI) at distal and shaft sites of right radius and tibia in a group of 40 prematurely born, otherwise normally developed and healthy young adults (17 women and 23 men, aged 18 to 27 years) and compared their data to corresponding data obtained from a group of 42 control subjects born term (20 women and 22 men, aged 18 to 28 years). Body height and weight were similar in both groups, but the preterm group had significantly lower BSI values at distal sites of tibia (approximately -16%) and radius (approximately -13%) and at tibial shaft (approximately -11%) as compared to control group. In the weight-bearing tibia, BMC was lower and the lower BSI values were mainly due to smaller total bone cross-sectional area. For unknown reason, this prematurity-associated detrimental effect seemed to concern more men than women. In contrast, prematurity was not associated with volumetric trabecular and cortical densities at any measured bone site while the typical sex differences in bone density were observed. We conclude that prematurity is associated with somewhat smaller cross-sectional bone dimensions in terms of body size in young adulthood. Due to the cross-sectional design, this study could not reveal specific reasons but they may pertain to nutrition during the neonatal period and living habits in general.