Pérdida visual secundaria a intoxicación inhalatoria y cutánea por metanol y tolueno. A propósito de un caso

Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favourable outcome during admission after treatment with ethanol in perfusion and corticosteroids.     

Effects of d-amphetamine injected into the nucleus accumbens on ethanol reinforced behavior

Rats, initiated to self-administer 10% (v/v) ethanol in an operant situation using the sucrose-fading procedure, received bilateral n. accumbens microinjections of d-amphetamine prior to operant sessions. Doses of 4 micrograms, 10 micrograms and 20 micrograms/brain were administered and some animals also received a 4 microgram/brain dose of LY171555. Three different effects were observed: increased, decreased and no change in total session responding. There was no clear relation between injection area in the n. accumbens and type of effect observed. For either an increase or decrease in total session responding, momentary response rates were decreased. Both d-amphetamine and LY171555 produced similar results. The data support the hypothesis that dopamine in the n. accumbens is involved with ethanol reinforced operant responding but in a complex manner.     

CT导引经皮穿刺注射无水乙醇治疗溶骨性骨转移瘤

目的探讨CT导引下经皮穿刺注射无水乙醇（CT～PEI）治疗溶骨性骨转移瘤的价值及安全性。方法对17例骨转移瘤患者（25个病灶）采用CT—PEI治疗，使用无水乙醇和超化碘油10：1的混合剂，用CT精确定位、准确穿刺瘤灶并密切监控无水乙醇弥散情况及用量，以减少并发症。对接近椎管及椎间孔的病灶，采用利多卡因实验性治疗以避免严重并发症。术前及术后定期CT检查，3例病人行同位素骨扫描检查，与治疗前检查进行对照研究。对患者随访3～30个月观察其临床疗效。结果所有患者经1次CT—PEI治疗后，疼痛即明显减轻，经2～3次CT-PEI治疗后疼痛完全缓解（CR）16例（24处病灶），疼痛部分缓解（PR）1例。术后随访3个月时，23处病灶内肿瘤组织均发生坏死，被高密度碘油混合液均匀浸润。其中，9处病灶体积缩小。随访3～30个月，除1例因周边出现新的肿瘤浸润灶而再次出现疼痛，其余病例转移瘤处止痛效果无反复。所有病例无严重并发症。结论CT—PEI是一种治疗骨转移瘤有效、微创、安全、简便的方法，使骨转移瘤内肿瘤组织坏死，最大限度的杀灭肿瘤细胞，从而达到满意的止痛效果，明显改善恶性肿瘤溶骨性转移病人的生活质量。     

Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

Ethanol regulated preference in rats

A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5–20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3–4 g/kg per 30 min). For example, pre-session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference.     

Differences in bioavailability between cocaine and cocaethylene and their implications for drug-reward studies

Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 µmol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 µmol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies.     

Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake

Previous work has reported that the 5-hydroxytryptamine (5-HT)_1A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6–250 µg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Neuro-toxic interaction in alcohol-treated,thiamine-deficient mice

Summary Groups of adult male mice were either fed a thiamine-deficient diet for 10 weeks and thereafter treated with ethanol by making them inhale vapourized cane spirit for 10 weeks, or given both treatments simultaneously. The brains of these mice were then searched for degeneration using both light and electron microscopy. No degenerating nerve cells were observed in any animal in the cerebral cortex, hippocampus, cerebellum, olfactory bulbs, midbrain or hindbrain. However, axon terminal degeneration was seen in the olfactory bulbs and deep cerebellar nuclei in mice given the combined treatment. No cerebellar degeneration was found and only little degeneration was present in the olfactory bulbs of mice given the two treatments at different times. Thus, the combined treatment of alcohol and thiamine deficiency produced more brain damage than the sum of that produced by the two treatments given separately. This represents the first experimental in vivo demonstration of a biochemical interaction between these two factors in alcohol-related brain damage. The findings of long-term animal treatment with models using thiamine antagonists are compared.Supported by the special Research Fund Programme of Monash University (Post-Doctoral Fellowship)