Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: Effects in human, rat and guinea-pig tissues in vitro and in pigs in vivo

1. We have investigated the cardiovascular pharmacology of the crude venom extract (CVE) from the potentially lethal, very small carybdeid jellyfish Carukia barnesi, in rat, guinea-pig and human isolated tissues and anaesthetized piglets. 2. In rat and guinea-pig isolated right atria, CVE (0.1-10 mu g/mL) caused tachycardia in the presence of atropine (I mu mol/L), a response almost completely abolished by pretreatment with tetrodotoxin (TTX; 0.1 mu mol/L). In paced left atria from guinea-pig or rat, CVE (0.1-3 mu g/mL) caused a positive inotropic response in the presence of atropine (1 mu mol/L). 3. In rat mesenteric small arteries, CVE (0.1-30 mu g/mL) caused concentration-dependent contractions that were unaffected by 0.1 mu mol/L TTX, 0.3 mu mol/L prazosin or 0.1 mu mol/L co-conotoxin GVIA. 4. Neither the rat right atria tachycardic response nor the contraction of rat mesenteric arteries to CVE were affected by the presence of box jellyfish (Chironex fleckeri) antivenom (92.6 units/mL). 5. In human isolated driven right atrial trabeculae muscle strips, CVE (10 mu g/mL) tended to cause an initial fall, followed by a more sustained increase, in contractile force. In the presence of atropine (I mu mol/L), CVE only caused a positive inotropic response. In separate experiments in the, presence of propranolol (0.2 mu mol/L), the negative inotropic effect of CVE was enhanced, whereas the positive inotropic response was markedly decreased. 6. In anaesthetized piglets, CVE (67 mu g/kg, i.v.) caused sustained tachycardia and systemic and pulmonary hypertension. Venous blood samples demonstrated a marked elevation in circulating levels of noradrenaline and adrenaline. 7. We conclude that C. barnesi venom may contain a neural sodium channel activator (blocked by TTX) that, in isolated atrial tissue (and in vivo), causes the release of transmitter (and circulating) catecholamines. The venom may also contain a 'direct' vasoconstrictor component. These observations explain, at least in part, the clinical features of the potentially deadly Irukandji syndrome.

A physiological product-release model for baculovirus infected insect cells

Existing models describe the product release from baculovirus infected insect cells as an unspecific protein leakage occurring in parallel with protein production. The model presented here shows that the observed product release of normally non-secreted proteins can be described through cell death alone. This model avoids the implicit non-physiological assumption of previous models that cells permeable to recombinant protein as well as trypan blue continue to produce protein. (c) 2005 Wiley Periodicals, Inc.

The stability of lipidic analogues of GnRH in plasma and kidney preparations: the stereoselective release of the parent peptide

The conjugation of a lipoamino acid to the N-terminus of Gonadotropin releasing hormone (GnRH) produces a lipophilic peptide from which the parent GnRH peptide is released into solution on treatment with plasma and kidney enzyme preparation. Our findings show that one stereoisomer of the Laa is cleaved very rapidly, providing a bolus dose of the peptide while the opposite stereoisomer is cleaved much more slowly, providing prolonged elevation of peptide concentration. The Laa-Glu linkage appears to act as a two phase prodrug system. © 2005 Elsevier Ltd. All rights reserved.

Hydrogen storage of magnesium-based nanocomposites system

Hydrogen storage in traditional metallic hydrides can deliver about 1.5 to 2.0 wt pct hydrogen but magnesium hydrides can achieve more than 7 wt pct. However, these systems suffer from high temperature release drawback and chemical instability problems. Recently, big improvements of reducing temperature and increasing kinetics of hydrogenation have been made in nanostructured Mg-based composites. This paper aims to provide an overview of the science and engineering of Mg materials and their nanosized composites with nanostructured carbon for hydrogen storage. The needs in research including preparation of the materials, processing and characterisation and basic mechanisms will be explored. The preliminary experimental results indicated a promising future for chemically stable hydrogen storage using carbon nanotubes modified metal hydrides under lower temperatures.

Factors in the selection of patients for conditional release from their first psychiatric hospitalization

Objective: This study examined a sample of patients in Victoria, Australia, to identify factors in selection for conditional release from an initial hospitalization that occurred within 30 days of entry into the mental health system. Methods: Data were from the Victorian Psychiatric Case Register. All patients first hospitalized and conditionally released between 1990 and 2000 were identified (N = 8,879), and three comparison groups were created. Two groups were hospitalized within 30 days of entering the system: those who were given conditional release and those who were not. A third group was conditionally released from a hospitalization that occurred after or extended beyond 30 days after system entry. Logistic regression identified characteristics that distinguished the first group. Ordinary least-squares regression was used to evaluate the contribution of conditional release early in treatment to reducing inpatient episodes, inpatient days, days per episode, and inpatient days per 30 days in the system. Results: Conditional release early in treatment was used for 11 percent of the sample, or more than a third of those who were eligible for this intervention. Factors significantly associated with selection for early conditional release were those related to a better prognosis ( initial hospitalization at a later age and having greater than an 11th grade education), a lower likelihood of a diagnosis of dementia or schizophrenia, involuntary status at first inpatient admission, and greater community involvement ( being employed and being married). When the analyses controlled for these factors, use of conditional release early in treatment was significantly associated with a reduction in use of subsequent inpatient care.

Calcium channels controlling acetylcholine release from preganglionic nerve terminals in rat autonomic ganglia

Little is known about the nature of the calcium channels controlling neurotransmitter release from preganglionic parasympathetic nerve fibres. In the present study, the effects of selective calcium channel antagonists and amiloride were investigated on ganglionic neurotransmission. Conventional intracellular recording and focal extracellular recording techniques were used in rat submandibular and pelvic ganglia, respectively. Excitatory postsynaptic potentials and excitatory postsynaptic currents preceded by nerve terminal impulses were recorded as a measure of acetylcholine release from parasympathetic and sympathetic preganglionic fibres following nerve stimulation. The calcium channel antagonists omega-conotoxin GVIA (N type), nifedipine and nimodipine (L type), omega-conotoxin MVIIC and omega-agatoxin IVA (P/Q type), and Ni2+ (R type) had no functional inhibitory effects on synaptic transmission in both submandibular and pelvic ganglia. The potassium-sparing diuretic, amiloride, and its analogue, dimethyl amiloride, produced a reversible and concentration-dependent inhibition of excitatory postsynaptic potential amplitude in the rat submandibular ganglion. The amplitude and frequency of spontaneous excitatory postsynaptic potentials and the sensitivity of the postsynaptic membrane to acetylcholine were unaffected by amiloride. In the rat pelvic ganglion, amiloride produced a concentration-dependent inhibition of excitatory postsynaptic currents without causing any detectable effects on the amplitude or configuration of the nerve terminal impulse. These results indicate that neurotransmitter release from preganglionic parasympathetic and sympathetic nerve terminals is resistant to inhibition by specific calcium channel antagonists of N-, L-, P/Q- and R-type calcium channels. Amiloride acts presynaptically to inhibit evoked transmitter release, but does not prevent action potential propagation in the nerve terminals, suggesting that amiloride may block the pharmacologically distinct calcium channel type(s) on rat preganglionic nerve terminals. (C) 1999 IBRO. Published by Elsevier Science Ltd.

Accommodative amplitude required for sustained near work

Purpose: Many practitioners base the prescription of near vision additions on the assertion that only one half or two-thirds of an individual’s amplitude of accommodation is sustainable for a prolonged period. To better understand how much eye focus needs to be restored for presbyopic corrections to be adequate, this study investigated the robustness of the pre-presbyopic human accommodative system during a sustained and intensive near vision task. Methods: Twenty-one pre-presbyopic volunteers (aged 26.1 ± 4.7 years) participated in the study. Binocular subjective amplitude of accommodation was measured before and after a prolonged reading exercise, using the RAF rule. During the 30 min reading task, the subject’s closest comfortable eye-to-text distance and pupil size was monitored. Accommodative accuracy to 0.2, 1.0, 2.0, 3.0 and 4.0 D stimuli was determined objectively using a validated binocular open-view autorefractor immediately before, and after the reading task. Results: Amplitude of accommodation (p = 0.09) and accommodative accuracy (p > 0.05) were statistically unchanged following the intensive near task. The mean proportion of accommodation exerted throughout the near exercise was 80.6% (range 45.3 ± 3.7 to 96.6 ± 4.3%), which increased as the task progressed (F = 2.24, p = 0.02). The mean percentage of accommodation utilised increased with subject age (r = 0.517, p = 0.016). Conclusion: The pre-presbyopic human accommodative system is robust to fatigue during intense and prolonged near work. A greater proportion of one’s amplitude of accommodation may be continuously exerted than previously suggested.

Sympathetic inhibition of accommodation after sustained nearwork in subjects with myopia and emmetropia

PURPOSE. The purposes of the present study were to assess the effect of a sympathetic inhibitory pharmacologic agent, timolol maleate, on the magnitude of nearwork-induced transient myopia (NITM) and its decay in different refractive groups for an extended near task duration and to determine the proportion of the young adult population manifesting effective sympathetic access under naturalistic closed-loop viewing conditions. METHODS. Ten subjects with emmetropia and 10 with myopia were tested. They read binocularly for 1 hour at a distance of 35 to 40 cm. NITM was calculated as the difference in distance refractive state after task as compared with before task immediately after reading. All subjects received timolol maleate to block the sympathetic nervous system and betaxolol as a control agent in independent test sessions separated by at least 3 days. Forty minutes after drug instillation, the NITM measurement procedure was repeated. RESULTS. Initial NITM magnitude was larger in subjects with myopia than in subjects with emmetropia before and after timolol instillation. Furthermore, NITM magnitude in subjects with sympathetic access was increased after timolol instillation. In contrast, with the control agent betaxolol, there was no increase. NITM decay duration to baseline was increased after timolol instillation in the subjects with myopia only. Only 15% of the subjects (n = 3 subjects with myopia) demonstrated effective and significant access to sympathetic facility. CONCLUSIONS. Subjects with myopia demonstrated an increase in decay duration with timolol, thus suggesting impaired sympathetic inhibition of accommodation. This may be a precursor for myopia progression in some persons.