SUMMARY1. The effects of hypoxia on the rat hippocampal CAI neurones in tissue slices of the rat brain were studied in vitro by intracellular recording.2. In response to superfusion of a hypoxic medium equilibrated with 95 % N2-5 % C02, a majority of the neurones showed a hyperpolarization of5-15 mV in amplitude and 4-12 min in duration. The hyperpolarization was, in turn, followed by a slow depolarization which within 20 min of hypoxic exposure reached a plateau level of about 25 mV above the pre-hypoxic resting potential. Both the initial hyperpolarization and subsequent depolarization were associated with a reduction in membrane resistance. 3. The hyperpolarization reversed in polarity at a membrane potential of -83 mV. There was an almost linear relationship between amplitude of the hyperpolarization and membrane potential. The hyperpolarization was markedly enhanced in potassium-free media and was depressed in high-potassium solutions.4. The hyperpolarization was not significantly affected by low-chloride or lowsodium medium or by solution containing tetraethylammonium (10 mM), 4-aminopyridine (1-5 mM) or caesium (3 mM). Moreover, intracellular injection of ethyleneglycol-bis-(fi-aminoethylether)N,N-tetraacetic acid (EGTA) did not alter the hyperpolarization. On the other hand, barium (0 5 mM)-containing medium reduced the amplitude of the hyperpolarization by 20-40 %.5. Superfusion of ouabain (5-7 puM)-containing medium in normoxic conditions produced hyperpolarizing and depolarizing responses similar to those elicited by hypoxic exposure. The slow depolarization was also mimicked by elevation of the extracellular potassium concentration to 10-20 mm.6. Evoked i.p.s.p.s were abolished within 4 min of hypoxic exposure while evoked e.p.s.p.s were maintained for about 20 min of hypoxic superfusion. Soma spikes of the neurones elicited by a depolarizing pulse were also well preserved. Their threshold was, however, raised, concomitant with a decrease in the peak amplitude.7. When the slice was reoxygenated after 20-40 min of hypoxic exposure, the neurones immediately began to repolarize and showed a transient hyperpolarization of 5-10 mV in amplitude and 1-2 min in duration. The membrane potential, input t To whom all correspondence and reprint requests should be sent.5-2 N. FUJIWARA AND OTHERS resistance and action potential returned to the pre-hypoxic levels after 15-20 min of reoxygenation. The amplitude of the reoxygenation-induced hyperpolarization was not significantly changed when the membrane was hyperpolarized or depolarized. The hyperpolarization was eliminated by potassium-free medium or solution containing ouabain (1 ,tM).8. In a minority of the neurones the slow depolarization was suddenly followed by a rapid depolarization, after which the neurones showed no functional recovery. Such an abrupt and irreversible depolarization appeared when the slow depolarization reached membrane potentials of -30 to -40 mV.9. The results suggest that hypoxia-induced hyperpolarization is due to an increase in voltag...

Poor maternal nutrition is a major contributor to the high incidence of low birth weight deliveries in developing countries. This study aimed to assess the impact of second trimester maternal dietary intake on gestational weight gain and neonatal birth weight. A longitudinal study was conducted in a tertiary care hospital in Sri Lanka. Participants were 141 pregnant women at 18–24 weeks gestation who were followed up until delivery. Maternal dietary intake was assessed using a validated Food Frequency Questionnaire at 21.1 ± 1.8 gestational weeks. Gestational weight gain was examined at the end of 28 weeks gestation and at the end of pregnancy. Energy and nutrient intakes were calculated using NutriSurvey 2007 (EBISpro, Willstaett, Germany) nutrient analysis software, modified for Sri Lankan foods. The mean total gestational weight gain of women with low carbohydrate intake (229–429 g/day) was 2.2 kg less than that of women with moderate carbohydrate intake (430–629 g/day) (95% confidence interval (CI) 0.428–4.083 kg; p = 0.016). Similarly, babies of women with low carbohydrate intake were 312 g lighter compared with those of women with a moderate carbohydrate intake (95% CI 91–534 g; p = 0.006). Our results suggest that second trimester maternal carbohydrate intake has significant impacts on total gestational weight gain and neonatal birth weight.

Ketamine is an IV anesthetic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine. Here, we evaluated a righting reflex to determine the general anesthetic/hypnotic potency of ketamine administered intraperitoneally to GluRepsilon1 knockout mice and compared these results with those for wild-type mice. Mutant mice were more resistant to ketamine than control mice. Unexpectedly, mutant mice were also more resistant to pentobarbital, which is thought not to interact with NMDAR at clinically relevant concentrations. Although these data in no way eliminate the possibility of the involvement of the NMDAR GluRepsilon1 subunit in mediation of ketamine anesthesia/hypnosis, they suggest the difficulties with interpretation of altered anesthetic sensitivity in knockout animal models.

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Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells.