Severe left heart obstruction with retrograde arch flow influences fetal cerebral and placental blood flow.

OBJECTIVE: Decreased middle cerebral artery (MCA) pulsatility index (PI) is a marker of fetal brain-sparing in placental insufficiency and it is also found in fetuses with severe congenital heart disease. This study sought to explore the impact of anatomical subtypes in fetal heart disease on MCA-PI and head growth. METHODS: We retrospectively reviewed fetal echocardiograms of pregnancies complicated by fetal hypoplastic left heart syndrome (HLHS; n = 42) with and without anatomic coarctation (n = 28 and n = 10, respectively), isolated severe aortic coarctation (n = 21), D-transposition of the great arteries (TGA; n = 11) and pulmonary outflow tract obstruction without forward flow across the pulmonary valve (POTO; n = 15), comparing observations with gestational age-matched controls (n = 89). No fetus had major extracardiac pathology or aneuploidy. MCA and umbilical artery (UA) PI, the cerebral placental ratio (CPR = MCA-PI/ UA-PI) and neonatal head circumference were obtained and expressed as Z-scores. RESULTS: Lower MCA-PI, higher UA-PI and lower CPR were observed in fetal HLHS and isolated coarctation with reversed arch flow (n = 6) (P < 0.001) but not TGA, POTO or isolated coarctation with antegrade arch flow (n = 15) compared with controls. No difference was found between HLHS with anatomical coarctation and those without; however, MCA-PI correlated positively with neonatal head circumference in HLHS with reversed distal arch flow (r = 0.33, P < 0.05). CONCLUSIONS: Severe left heart obstruction with reversed aortic arch flow is associated with altered fetal cerebral blood flow, and in these conditions, MCA-PI positively correlates with head growth. Anatomical arch obstruction itself may not be a contributing factor to altered MCA flow in fetal HLHS.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Ivermectin is better than benzyl benzoate for childhood scabies in developing countries.

OBJECTIVE: To compare single dose oral ivermectin with topical benzyl benzoate for the treatment of paediatric scabies. METHODS: An observer-blinded randomized controlled trial was undertaken at Vila Central Hospital, Vanuatu. One hundred and ten children aged from 6 months to 14 years were randomized to receive either ivermectin 200 micro g/kg orally or 10% benzyl benzoate topically. Follow up was at 3 weeks post-treatment. Primary outcome measures were the number of scabies lesions, the itch visual analogue score and nocturnal itch. Secondary outcome measures were the skin's reaction to treatment, the passage of worms in stool and other side effects. RESULTS: Eighty patients completed the study protocol. There was no significant difference between the two treatments; both produced a significant decrease in the number of scabies lesions seen at follow up. Ivermectin cured 24 out of 43 patients (56%), and benzyl benzoate 19 out of 37 patients (51%) at 3 weeks post-treatment. No serious side effects were noted with either treatment, but benzyl benzoate was more likely to produce local skin reactions (P = 0.004, OR 6.4, 95% CI 1.6-25.0) CONCLUSIONS: Ivermectin is cheap and effective in the treatment of paediatric scabies. Ivermectin has minimal observed toxicity and has the additional beneficial effects of antiparasitic action in onchocerciasis, filariasis and strongyloidiasis. Ivermectin is better than benzyl benzoate for the treatment of paediatric scabies in developing countries.

A comparison between lecture and videotape inservice for certified nursing assistants in skilled nursing facilities.

OBJECTIVE: Certified Nursing Assistants (CNA) provide most of the direct patient care in skilled nursing facilities (SNF). CNAs undergo mandatory inservice education regarding a variety of clinical conditions, but high CNA turnover and diverse cultural and educational backgrounds are persistent obstacles to overall staff education. A standardized, easily administered, highly reproducible training intervention would be valuable. We compared the efficacy of videotape versus standard lecture for inservice education relating to topics of dementia care, restraint use, and falls. DESIGN: A prospective randomized study. SETTING: Certified Nursing Assistants were recruited from three SNFs in San Diego County California between November 1997 and August 1998. PARTICIPANTS: The 82 CNAs who participated in the study were all CNA certified in California, employees of the study SNFs, and provided direct clinical care to SNF residents. All participants received regular inservice training. INTERVENTIONS: (1) Standard inservice lecture, (2) Videotape of inservice lecture material supplemented with brief clinical video vignettes. MAIN OUTCOME MEASURES: Scores on a 72-item multiple choice/true-false examination. MAIN RESULTS: Both lecture and video inservice education were effective in this CNA population. Test scores were significantly higher for both inservice groups compared with the control group (P < 0.001). There was no statistically significant difference between test scores for the two intervention groups (control = 63.1 +/- 8.2%, lecture = 78.2 +/- 8.9%, video = 77.9 +/- 11.2%). Knowledge retention was similar between the two intervention groups at 4 months. Lecture subjects who scored highest were more likely to have family members with dementia (P = 0.037), and video subjects who scored highest were younger (P = 0.007). CNA video subjects who scored highest on the examination were more likely to have English as their primary language compared with the highest scoring CNA lecture subjects (P = 0.012). CONCLUSIONS: Compared with control group scores, videotape and lecture inservice interventions were equally effective at increasing and maintaining test scores. The ease of frequent video intervention and the identification of learner characteristics most suited to the video format make audiovisual education a potentially powerful medium for CNA training. These data have important implications for future educational interventions in the SNF.

Activation of BLV transcription by NF-kappa B and Tax.

Bovine leukemia virus (BLV) is the causative agent of bovine leukosis, a naturally occurring fatal disease in cattle. BLV transcription is regulated by cellular transcription factors and the virally encoded oncoprotein Tax. In this report, we investigated the functional role of the putative NF-kappa B binding site recently identified in the BLV promoter. Our studies indicate that the kappa B binding motif acts as a functional enhancer in the presence of the cellular NF-kappa B proteins. Furthermore, the kappa B site together with a single 21-bp repeat confers strong activation of BLV transcription in the presence the NF-kappa B proteins and Tax. These results suggest that cellular NF-kappa B may be involved in the regulation of BLV transcription and activation of the virus from latency.

Acidosis of rat dorsal vagal neurons in situ during spontaneous and evoked activity.

1. Rat brainstem slices were taken for simultaneous measurements of intracellular pH (pHi) and membrane currents or potentials in dorsal vagal neurons, dialysed with the pH-sensitive dye BCECF. 2. Intrinsic intracellular buffering power was 18 mM per pH unit, as determined by exposure to trimethylamine in CO2/HCO3(-)-free, Hepes-buffered saline. 3. Tonic spike activity led to a stable fall in pHi of 0.05-0.2 pH units from a baseline of 7.19 in current-clamp mode, whereas depolarization from -60 to 0 mV for 1 min in voltage-clamp mode produced an intracellular acidification of 0.3 pH units. The depolarization-evoked fall in pHi was suppressed by 1 mM Ni2+ or 0.2 mM Cd2+, but not by 0.5 microM TTX or CO2/HCO3(-)-free saline. 4. Kainate (100 microM) led to an an inward current of -620 pA and a threefold increase in membrane conductance, accompanied by a fall in pHi of 0.33 pH units. 5. GABA (1 mM) evoked a bicuculline-blockable conductance increase and fall in pHi of up to 0.5 pH units. The GABA-induced pHi decrease, but not the conductance increase, was suppressed in Hepes solution. 6. Neither tonic spike activity, nor resting current or conductance were markedly changed upon Hepes-induced intracellular alkalinizations of up to 0.35 pH units, or by an anoxia-induced fall in pHi of a maximum of 0.36 pH units. 7. The data show that neuronal activity produces profound changes in pHi. It appears that spontaneous spike discharge of dorsal vagal neurons is rather tolerant of major perturbations in pHi.

The effect of 5-HT and selective 5-HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro.

1. Whole-cell patch-clamp recordings were made from 142 visually identified rat dorsal vagal preganglionic neurones (DVMs). Applications of 5-hydroxytryptamine (5-HT, 20 microM, 2 min) elicited a slow depolarization (8.2 +/- 0.5 mV, n = 59) in 95% of the cells tested, accompanied by an increase in excitability. In (68%) of DVMs the depolarization was associated with an increase in apparent membrane resistance (Rmt 22.7 +/- 2.2%). These depolarizations and increases in Rm (14.3 +/- 2.6%, n = 8) were maintained in a medium which blocked synaptic transmission. 2. The response to 5-HT was associated with a reversal potential (Erev) of -91 +/- 1 mV at an extracellular K+ concentration (LK+]o) of 4.2 mM. This correlated well with the K+ equilibrium potential (Ek = -89 mV). 3. The depolarizing effect of 5-HT was attenuated by the 5-HT2A/2C receptor antagonists, ketanserin (1 microM), LY 53,857 (1 microM) and the 5-HT1A/2A receptor antagonist, spiperone (1 microM). The 5-HT1A receptor antagonist, pindobind 5-HT1A (5 microM), had no effect on the depolarizing response to 5-HT. 4. The effect of 5-HT was mimicked by the 5-HT2A/2C receptor agonist, alpha-methyl-5-HT (50 microM), the 5-HT1 receptor agonist, 5-carboxamidotryptamine (20 microM) and the putative 5-HT4 agonist, 5-methyoxytryptamine (5 microM). The selective 5-HT4 receptor antagonist, GR113808, had no effect on the depolarizing effect of 5-HT or 5-MEOT on DVMs. 5. The 5-HT3 antagonists, MDL 72222 (10 microM) and ICS-205-930 (1 and 10 microM), partially reduced the effect of 5-HT. The 5-HT3 receptor agonist, 2-methyl-5-HT (100-300 microM), excited a proportion of neurones tested (56%) by evoking a depolarizing and/or an increase in postsynaptic potentials (p.s.ps). 6. These results are consistent with direct, postsynaptic actions of 5-HT on DVMs via 5-HT2A receptors, being mediated, in part, by the reduction of K+ conductance.

Tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat medulla: evidence for a presynaptic locus.

1. Whole cell voltage-clamp recordings were made from dorsomedial nucleus tractus solitarii (dmNTS) neurons in coronal rat medullary slices. Synaptic activity was evoked by electrical stimulation in the region of the tractus solitarius (TS). Excitatory postsynaptic current/inhibitory postsynaptic current (EPSC/IPSC) complexes were recorded with K-gluconate-containing electrodes. Monosynaptic, gamma-aminobutyric acid-A (GABAA) receptor-mediated evoked IPSCs (evIPSCs) were recorded in the presence of D(-)2-amino-5-phosphonopentanoic acid (AP5, 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM) with CsCl-containing electrodes. Control synaptic stimulation was applied at 0.1 Hz. 2. Tetanic stimulation (50 Hz, 2 s) produced an increase in the 10-90% rise time of the evIPSC component of mixed EPSC/IPSC complexes (assessed at Vhold = 0 mV) in three of eight recordings that remained significantly potentiated above control for > 15 min. This potentiation was further characterized with the use of Cs-containing electrodes. Tetanus similarly potentiated the amplitude of monosynaptic evIPSCs by 168.0 +/- 10.4% (mean +/- SE) control at 15 min posttetanus in 49 of 114 recordings. This tetanus-induced sustained potentiation of monosynaptic evIPSCs (TIP) was reproducible after recovery to control levels. 3. High Mg2+/low Ca2+ solutions reversibly blocked induction of TIP. TIP was reproducible in slices treated (> 7 min) with the N-type voltage-dependent Ca2+ channel (VDCC) antagonist omega-conotoxin-GVIA (1 microM) or L-type channel blocker nimodipine (10 microM), but not in those slices treated with either omega-agatoxin-IVA (200 nM, 20 min) or omega-conotoxin-MVIIC (2 microM). 4. The GABAB receptor antagonist CGP35348 (100 microM) reversibly blocked induction of TIP, reduced resting, and blocked tetanus-induced increases in spontaneous IPSC frequency. Spontaneous IPSC amplitude was unaffected by CGP35348. 5. These results suggest a presynaptic locus for TIP in dmNTS, which depends in part on Ca2+ influx through P/Q-type VDCCs.

Identification of an NF-kappa B binding site in the bovine leukemia virus promoter.

Although the mechanism by which bovine leukemia virus (BLV) induces neoplastic transformation of the host B cells is unknown, it is likely that critical interactions between cellular DNA-binding proteins and the virus are involved. We have used DNase I protection (footprinting) assays to construct a map of protein-DNA interactions on the 5' long terminal repeat of BLV. In addition to the three cyclic AMP response elements previously reported, we have also found an NF-kappa B binding site between -118 and -70 nucleotides upstream of the RNA start site. This site binds several members of the kappa B family of proteins, including p49, p50, and p65, in both footprint and electrophoretic mobility shift assays and functions as an enhancer element when inserted upstream of the chloramphenicol acetyltransferase gene. NF-kappa B may be a critical nuclear binding protein that regulates both viral replication and key cellular genes in BLV-infected B cells.

GABAB receptors modulate a tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat nucleus tractus solitarii in vitro.

Whole-cell recordings were made in the nucleus tractus solitarii (NTS) in transverse brainstem slices from rats. Monosynaptic GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) or potentials (IPSPs) were evoked (0.1-0.2 Hz) by electrical stimulation within and medial to the tractus solitarius in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) or 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microM) and D-amino-5-phosphonopentanoic acid (APV; 50 microM). A brief period of tetanic stimulation (20 Hz, 2 s) resulted in posttetanic (< 5 min, 69 of 73 recordings) and sustained potentiation (> 15 min, 31 of 73 recordings) of the IPSP/Cs. Sustained potentiation was not due to alterations in the reversal potential of IPSP/Cs. Both pre- and post-tetanus IPSP/Cs were completely blocked by the GABAA antagonist bicuculline (10 microM). Postsynaptic responses to pressure ejection of the GABAA-receptor agonist muscimol were unaltered in cells displaying sustained potentiation. Sustained potentiation of IPSP/Cs could be induced by tetanus in the presence of either metabotropic glutamate receptor antagonists or bicuculline. However, sustained potentiation could not be induced in the presence of the GABAB-receptor antagonists 2-OH-saclofen (400 microM) or CGP35348 (3-amino-propyl-(diethoxymethyl)phosphinic acid, 100 microM), although a subsequent tetanus following washout induced sustained potentiation. Posttetanic potentiation was unaffected by GABAB-receptor antagonists. These data suggest that neuronal or terminal excitability of GABAergic interneurons in the NTS is enhanced following brief periods of increased frequency of activation in vitro. This novel phenomenon within the rat medulla may be involved in the temporal modulation of autonomic reflex sensitivity observed during certain behavioral states, such as the defense reaction.

A study of sympathetic preganglionic neuronal activity in a neonatal rat brainstem-spinal cord preparation.

Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonatal rat brainstem-spinal cord preparation. Neurones were identified as SPNs as they were: (i) activated at constant latencies (2-10 ms) following stimulation of the ventral root, which indicated antidromic activation and (ii) recorded at sites located either in the intermediolateral cell column or the intercalated nucleus of the thoracic spinal cord. Over one-third of the neurones (n = 17) recorded displayed ongoing activity with firing frequencies of 0.3-5 Hz. Of the neurones analyzed only one showed a very obvious phasic firing pattern. Dorsal root stimulation evoked firing in 16 of 26 SPNs recorded from the same spinal segment (6 of 10 with ongoing activity). The types of responses observed varied between neurones. The excitation of all neurones was characterised by a response occurring at a latency of 6-50 ms. In addition, SPNs in 'spinalised' preparations (n = 2) responded with latencies of 10-40 ms, similar to those observed in the intact preparation. The latencies of responses in SPNs were longer and more variable than those observed in ventral horn motor neurones. This indicates that a spinal polysynaptic pathway was involved in mediating these responses. In 7 SPNs dorsal root stimulation also elicited longer latency responses which were observed up to 1000 ms after stimulation. These responses may involve activation of bulbospinal and/or propriospinal pathways. These results show that the neonatal rat brainstem-spinal cord preparation is viable for studying SPNs and that dorsal root-SPN reflexes are intact.

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

1. Intracellular and whole-cell patch recordings were made from sixty-seven neurones located in the nucleus tractus solitarii (NTS) in transverse slices of rat brainstem. 2. Baclofen at concentrations of 2-20 microM caused hyperpolarization from normal resting membrane potentials (Vm). This response was associated with a decrease in input resistance (Rm) tested by current pulses in discontinuous current clamp mode when membrane potential was restored to control level by current injection. In single electrode discontinuous voltage clamp mode, baclofen at these concentrations caused a small (< 50 pA) outward current associated with increased membrane conductance measured by voltage steps from holding potentials (Vh) of -50 or -60 mV. Current-voltage relations at these Vhs and the results of varying Vh between -50 and -110 mV during responses to baclofen gave a reversal potential of -73 mV. The amplitudes of baclofen responses were related to K+ concentration tested by comparing responses in media containing 1-24 mM extracellular K+, indicating that postsynaptically baclofen acts via a K+ conductance. 3. These effects were still apparent in the presence of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and also in medium containing a combination of Co2+, the excitatory amino acid antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and the GABAA antagonist bicuculline which blocked synaptic activity. 4. The amplitude and frequency of spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic currents (spPSCs) were reduced by baclofen at concentrations (1 microM or less) which had no effect on membrane potential or holding current in current or voltage clamp recordings respectively. 5. The amplitude of evoked excitatory (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced by low concentrations of baclofen (250 nM-1 microM) which did not produce discernible postsynaptic responses. 6. In order to examine the effects of baclofen on excitatory synaptic events without contamination with inhibitory events, stimulation of the TS was carried out in the presence of bicuculline. Conversely to investigate actions on purely inhibitory synaptic responses experiments were carried out with CNQX in the bathing solution. Inhibitory synaptic responses could still be evoked, presumably by stimulation of interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to baclofen than EPSPs/EPSCs. 7. The effects of baclofen on membrane potential or holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 microM) confirming that baclofen was acting at gamma-aminobutyric acid (GABA)B receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro.

Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT, 100 microM) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5-HT, 100 microM) depolarized 86% of NTS neurons at resting membrane potential (Vm). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100 microM) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1 microM decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10 microM) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS.

Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics.

1. The effects of the volatile anaesthetics enflurane, halothane and isoflurane on gamma-aminobutyric acid (GABA)A receptor-mediated chloride currents were studied in cultured rat hippocampal neurones. Transient current responses were obtained by brief pressure application of GABA to the cell body of neurones under voltage clamp. 2. All three anaesthetics increased the peak amplitude and duration of current 2. All three anaesthetics increased the peak amplitude and duration of current responses to brief applications of GABA. These effects were fully reversible, and did not involve alterations in the reversal potential for GABA responses. 3. The experimental concentrations of anaesthetics were measured directly using gas chromatography. The enhancement of GABA currents increased with increasing anaesthetic concentration. Clinically effective concentrations of anaesthetics (between 1 and 1.5 times MAC (minimum alveolar concentration) produced significant enhancement of GABA currents. 4. These results demonstrate that the changes in the time course of synaptic inhibition reported in the presence of the volatile anaesthetics are likely to result from modification of the function of postsynaptic GABAA receptor-channel complexes. These findings also support the hypothesis that GABAA receptor complexes serve as common molecular target sites for a variety of structurally diverse anaesthetic molecules.

Investigation of inositol hexakisphosphate actions in rat nucleus tractus solitarius in vitro.

Intracellular recordings from neurones in slices of rat brainstem containing the nucleus tractus solitarius were made to examine the effects of inositol hexakisphosphate (IP6) in a region where cardio-depressant effects had been reported in vivo in the same species. Bath application of IP6 failed to consistently alter the excitability, membrane potential or resistance even at concentrations up to 44 microM. Glutamate application (1-1.5 mM) was, however, effective in increasing excitability and depolarising these neurons. Thus, the neuronal mechanisms underlying the cardiovascular effects reported in vivo have not been resolved.

Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease.

We looked for antibodies against endothelial cells, monocytes, fibroblasts, lymphocytes and Epstein-Barr virus transformed lymphocytes in the sera of 28 elderly and 18 middle-aged patients with atherosclerotic peripheral arterial disease and 13 controls. Inclusion criteria were symptomatic peripheral arterial disease with intermittent claudication and ankle/radial Doppler pressure ratio less than 0.7 in the patient group and greater than 1 in the controls. The sera were tested using a standard cytotoxic technique against a cell panel of monocytes, T and B lymphocytes from 5 donors, and against endothelial cells, fibroblasts and Epstein-Barr virus transformed lymphocytes from one umbilical cord vein and blood. The sera of 30 of 46 (65.2%) patients showed toxicity against monocytes from at least one member of the cell panel and 12 of 19 sera tested (63%) reacted with endothelial cells. Only one of the control sera was positive against monocytes and none reacted with endothelial cells. None of the sera of either patients or controls contained cytotoxic antibodies against T and B lymphocytes, Epstein-Barr virus transformed lymphocytes or fibroblasts. The selective cytotoxicity suggests that the antibodies detected are not against HLA-antigens (which are expressed by normal lymphocytes and Epstein-Barr virus lymphocytes). Our results suggest that immune phenomena occur in atherosclerosis.

Purine modulation of cholinomimetic responses in the rat hippocampal slice.

Iontophoretic application of carbachol caused excitation of CA1 neurones and decreased the amplitude of antidromic CA1 population spikes recorded extracellularly. Adenosine, adenosine triphosphate (ATP) and the purine analogues N-ethylcarboxamide adenosine (NECA) and R- and S-phenylisopropyladenosine (PIA) reduced the effects of carbachol on single cell firing and on the population spike. Responses to excitatory amino acids were unaffected by adenosine except for a small depression of kainate and N-methyl-D-aspartate responses at high concentrations. The rank order of potency for the purine reduction of carbachol responses was R-PIA = S-PIA = NECA much greater than adenosine greater than ATP. The actions of purines and purine analogues were antagonized by 8-phenyltheophylline (8-PT) and other xanthine antagonists. Application of 8-PT and other xanthines without prior exposure to purines frequently resulted in marked potentiation of carbachol responses. Thus in the hippocampus, responses to the cholinomimetic carbachol are markedly and selectively reduced by purines acting at the P1 purine receptor type and it appears that endogenous levels of adenosine limit the effects of cholinergic agents.

Direct excitatory effects of neuropeptide Y (NPY) on rat hippocampal neurones in vitro.

Intracellular recordings from granule cells of the rat dentate gyrus show neuropeptide Y (NPY) applied by pressure ejection from pipettes containing 1.2-12 microM by pressures of less than 200 kPa for 1-5 s in duration to consistently evoke membrane depolarisations accompanied by a reduction in membrane resistance. The depolarisations were accompanied by an increase in excitability. Since the depolarisations evoked by NPY were not attenuated by either tetrodotoxin or kynurenic acid a direct excitatory action of NPY is postulated.

Antimicrobial alternatives for calf diarrhea: enteric responses to Escherichia coli, deferoxamine, or gallium in neonatal calves.

Intestinal malabsorption or transferable resistance in enteric bacteria are potentially serious complications of routine oral administrations of antibiotics. On the basis of reports on antimicrobial effects of host iron sequestration and on synthetic iron chelators or competitors in vitro, 2 iron antagonists were studied for their potential as alternative antimicrobials for Escherichia coli diarrhea. Deferoxamine, a fungal iron chelator used to treat acute iron intoxication, and elemental gallium, a competitive inhibitor of iron activity in metabolic enzyme systems, were examined for their effects on enteric morphology and function in neonatal calves. Twelve male calves were allotted to 4 groups: (1) given nonpathogenic E coli (control); (2) given enterotoxigenic B44 E coli; (3) given deferoxamine (50 mg/kg, twice a day); and (4) given gallium (4 mg/kg, twice a day). Calves were studied for 8 days, including the conduct of oral glucose and lactose tolerance tests on days 1, 3, and 7. By day 7, according to oral glucose and lactose tolerance tests, peak plasma glucose concentrations in all calves of groups 2, 3, and 4 were lower than those values in controls. The frequency of diarrhea was significant in all treated calves, and disease was most severe in the deferoxamine-treated calves. Quantitative cultural examination on day 8 showed significant numerical increases of jejunal and ileal E coli and ileal lactobacilli in deferoxamine-treated calves (group 3) and of ileal streptococci in gallium-treated calves (group 4) and showed jejunal and ileal overgrowths of Saccharomyces yeast in deferoxamine-treated calves.(ABSTRACT TRUNCATED AT 250 WORDS)