Antifungal Activity of a New Triterpenoid Glycoside from Pithecellobium racemosum (M.)

Purpose. In a continuation of our search for novel antifungal compounds from higher plants, the standard extract of the bark of Pithecellobium racemosum was found to have good activity against important AIDS-related opportunistic yeasts. Methods. The extract was subjected to bioguided fractionation using silica gel column chromatography which led to purification of triterpene glycosides. The structures of these compounds were determined by a combination of spectroscopic (IR, NMR, HRMS) and chemical methods. Results. Compound 1 is a new glycoside, 3-O[-L-arabinopyranosyl (1 -2)][-L arabinopyranosyl (1 -6)]2-acetoamido-2-deoxy--D-gluco-pyranosyl oleanolic acid and Compound 2 was identified as the known compound 3-O-[-L-arabinopyranosyl (l-2)]-L-arabinopyranosyl (1-6)] 2-acetamido-2-deoxy--D-glucopyranosyl echinocystic acid. Conclusions. Compound 1 is a new glycoside, 3-O-[-L-arabinopyranosyl (1-2)]-L-arabinopyranosyl (l-6)]-2-acetoamido-2-deoxy--D-glucopyranosyl oleanolic acid and exhibits moderate antifungal activity against T. mentogrophytes, C. albicans and S. cerevisiae with MIC values of 6.25, 12.5 and 12.5 g/ml respectively.     

Characterization of the binding of [3H]-SB-204269, a radiolabelled form of the new anticonvulsant SB-204269, to a novel binding site in rat brain membranes

1. SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side-effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [³H]-SB-204269 in rat forebrain membranes.
2. Specific [³H]-SB-204269 binding was saturable and analysis indicated binding to a homogenoeous population of non-interacting binding sites with a dissociation constant (K_D) of 32±1 nM and a maximum binding capacity (B_max) of 253±18 fmol mg⁻¹ protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na⁺, K⁺, Ca²⁺ or Mg²⁺ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues.
3. Specific [³H]-SB-204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB-204269 and its enantiomer SB-204268 for the binding site. The affinities of analogues of SB-204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action.
4. None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [³H]-SB-204269 binding site. A wide range of drugs active at amino acid receptors, Na⁺ or K⁺ channels or various other receptors did not demonstrate any affinity for the binding site.
5. These studies indicate that SB-204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.

     

Access to health care. A conceptual framework and its relevance to health care planning

Despite some serious past efforts to clarify its multiple dimensions and meanings, access to health care has remained a rather elusive concept, hampering the work of health care policymakers and professionals as they endeavor to effect meaningful health care reform. This article provides perhaps the most detailed clarification of the access concept, especially the crucial linkages among the various access dimensions, and presents a comprehensive conceptual framework for evaluation and planning activities as they relate to people's access to health care services. The proposed conceptual model recognizes access as the outcome of a process involving the interplay between the characteristics of the health care service system and of potential users in a specified area, and moderated by health care related public policy and planning efforts. An elaborate typology of access, incorporating four pairs of access dimensions, is also derived. This atomization of the concept allows us to focus on specific aspects of the access to health care problem, and to develop precise outcome indicators of health system performance for evaluative purposes. Further, it enables the access concept and its pertinent dimensions to be put into proper perspective when assessing the health care access situation in a specific national or regional context. The relevance of the proposed access model and the typology to health care planning in general, and to spatial planning of health care service systems in particular, is also discussed.     

Country watch: Pakistan

75-80% of the general public in Pakistan visits a private practitioner first in the case of illness. Private practitioners are therefore an important primary target for HIV/AIDS training and clinics are an ideal site in which to convey HIV prevention messages. The Physicians Forum for Family Planning in 1991 conducted a random survey of private practitioners' knowledge, attitudes, and beliefs about AIDS. 48% did not know what AIDS stands for, 68% were unaware of the meaning of HIV, none could identify all three modes of HIV transmission, 33% knew that contaminated needles can transmit HIV, and none knew about perinatal transmission. Training workshops were therefore organized to improve HIV/AIDS awareness among private practitioners, concentrating upon transmission, risk factors, clinical signs and symptoms, HIV prevention, HIV and contraception, the role of private practitioners in prevention and care, and counseling. 398 private practitioners had participated in the workshops by the end of September 1993. When pre- and post-workshop awareness were compared, correct answers had increased from 45% to 95%. It was difficult, however, to convince participants that kissing is not risky. It was also a challenge to make them understand the difference between HIV infection and AIDS. Interactive discussions and slide talks were particularly popular. Counseling on sexuality and clinical care for and counseling people with HIV/AIDS are areas for follow-up for those interested. A post-intervention evaluation in 1994 found that the workshops had a significant impact upon the clinical practice of private practitioners.     

Manganese in gasoline. Council on Scientific Affairs, American Medical Association

This report responds to a resolution that asked the American Medical Association (AMA) to take action to reduce potential health risks from the use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline. Information for this report was derived from a search of the MEDLINE database and references listed in pertinent articles, as well as through communications with medical and public health experts. Based on this information, the AMA Council on Scientific Affairs determined that there is insufficient scientific evidence to assess the public health impact of MMT use. While limited evidence indicates that general-population exposures to manganese from the use of MMT in gasoline are low, more research is needed to determine possible health effects from long-term, low-dose exposures to MMT and its combustion products. Until such data are available, educational and informational strategies should be developed to improve public awareness of the health and environmental issues surrounding MMT use.     

Identifying patients at low risk of death from cardiac failure after operation for postinfarct ventricular tachycardia

BACKGROUND: In unselected patients, cardiac failure accounted for most deaths after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia (VT). This study aimed to determine whether patients at low risk of this outcome could be predicted from a retrospective analysis of variables from 100 consecutive ER patients. METHODS: Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT. RESULTS: Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.     

Aneurysms complicating pulmonary autograft procedure for aortic valve replacement

Aneurysm formation in the left ventricular outflow tract related to the proximal end of the pulmonary autograft after the Ross procedure was present in 2 patients. Both occurred late after operation and were associated with prolapse of a leaflet of the autograft and significant regurgitation. Both were repaired with no immediate complications. There was no evidence of infection at time of operation. The probable mechanisms underlying this complication and the possibilities of avoiding it are discussed.     

Effects of low-dose isoflurane on saccadic eye movement generation

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.