A convenient multipurpose mouse restrainer.

A convenient, inexpensive, easily constructed mouse restrainer is described and illustrated. The restrainer has the advantage over other models that while the animal is effectively immobilized, time-consuming and potentially injurious binding of extremities is avoided, and selected areas such as the back, extremities and tail remain accessible for manipulations.

Metrifonate improves associative learning and retention in aging rabbits.

The cholinergic system is known to show deterioration during aging and Alzheimer's disease (AD). In response, a therapeutic approach to AD has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase (ChE) inhibitors. In this study treatment with the long-lasting ChE inhibitor metrifonate facilitated acquisition and retention of eyeblink conditioning in aging rabbits. Metrifonate treatment resulted in steady-state, dose-dependent acetylcholinesterase (AChE) inhibition in red blood cells. Maximal behavioral efficacy was achieved with AChE inhibition of approximately 40%, with no further improvements resulting from increased levels of inhibition. Metrifonate was behaviorally effective in the absence of the severe side effects that can plague ChE inhibitors, supporting metrifonate as a possible treatment for the cognitive deficits resulting from normal aging and AD.

Elution of renal antischistosome antibodies in human schistosomiasis mansoni.

Elution of complexed immunoglobulins was carried out in renal tissue obtained at autopsy from schistosomiasis mansoni and control cases. Substantial amounts of IgG were found in acid eluates of 2 of 5 schistosomiasis cases and 2 of 3 controls. The IgG from schistosomiasis cases produced specific indirect immunofluorescence reactions in gut and tegument of sections of adult Schistosoma mansoni; no reactivity was present against egg granulomas, cercariae, or mouse liver tissue. Control case eluates produced no fluorescence with S. mansoni antigens.

Trypanosoma cruzi in the opossum Didelphis marsupialis: an indirect fluorescent antibody test for the diagnosis and follow-up of natural and experimental infections.

The use of an indirect fluorescent antibody test (IFAT) performed in a "sandwich" technique has demonstrated: (i) the usefulness of the test for the diagnosis of Trypanosoma cruzi infection in the opossum Didelphis marsupialis; (ii) the existence of differences in the serological response of the opossum, that were related to the parasite strain and were clearly evident during the follow-up of experimental infections in laboratory born specimens; (iii) that, despite a good correlation between serological and parasitological examinations, IFAT was the most sensitive diagnostic test used, followed by xenodiagnosis; and, (iv) that in general, the opossum D. marsupialis seems to be a good responder to T. cruzi antigens.

Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits.

The cholinergic system is known to show deterioration during aging and Alzheimer's disease. In response, a therapeutic approach to Alzheimer's disease has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase inhibitors. In this study treatment with the long-lasting cholinesterase inhibitor metrifonate enhanced acquisition of eyeblink conditioning in aging rabbits without producing interfering side effects. The effects of metrifonate on central and peripheral cholinesterase activity were evaluated, as was the involvement of plasma atropine esterase activity on the central and peripheral response to metrifonate. Results demonstrate that metrifonate can produce predictable, dose-dependent ChE inhibition. Associative learning in the aging rabbit was improved by metrifonate-induced steady state ChE inhibition within a range of 30-80%. Metrifonate was behaviorally effective in the absence of the severe side effects which typically plague cholinesterase inhibitors, suggesting that metrifonate is a possible treatment for the cognitive deficits resulting from normal aging and Alzheimer's disease.

International access to the Chinese medical literature through MEDLINE.

This article reviews, for authors publishing in the Chinese literature, the characteristics of MEDLINE users, the format of MEDLINE citations and the main retrieval strategies used with the system. References were retrieved and data collected through MEDLINE searches of the database 1988-June 1992. Thirty-six indexed journals from the People's Republic of China (PRC) were analyzed. The items of a MEDLINE citation are described. Titles of Chinese journals are listed in English as well as Chinese in the annual "List of Serials Indexed" of Index Medicus. Articles from journals in the PRC are indexed at the China MEDLARS Center, Beijing, PRC. For the 36 journals analyzed, 12,530 citations appeared in MEDLINE during the search period. Basic search strategies are described. Users doing author searches may have difficulties with common Chinese surnames, especially if only one given name initial is used. Journal searches of specialty journals, as well as address field searches for publications from a particular institution, may be helpful to scientists planning a visit to China. Effective use of MEDLINE has become an opportunity and responsibility for scientists and physicians over the world. Suggestions for preparation of English titles and abstracts to assure optimal information transfer and retrieval efficiency are: think about your audience; do not waste words; include key features in the title; be consistent with names and affiliations; use MeSH terms; include important non-MeSH terms in text; use structured abstracts; and obtain MEDLINE printouts of your own citations.

Women's health in the People's Republic of China: some challenges of modernization.

OBJECTIVE: To identify aspects of the health of Chinese women throughout their lifespan which may paradoxically be threatened by modernization and to suggest relevant interventions through medical practice, education and research to meet these challenges. DATA SOURCES: Six risk areas were selected as examples: infant sex ratios; tobacco use by girls; respiratory illness plus anemia; psychosocial stress; osteoporosis; and dementia. Articles and other databases, through article citations, and through consultations with Chinese medical professionals. DATA SELECTION: Studies were selected which described clinical investigations, health care policy, or conditions of women in the People's Republic of China (PRC). Preference (but not exclusivity) was given to articles in internationally available publications, in English, and to authors working in the PRC. DATA EXTRACTION: Study quality, specific descriptive information concerning population, samples, and outcome measures were evaluated. DATA SYNTHESIS: Data documenting the present and future significance of these health threats are described, and current and potential interventions to address these problems through medical practice, education and research are outlined. CONCLUSION: Important issues in women's health are currently recognized in the PRC; problems occur in assigning priorities in the face of a large population and limited resources. The Chinese medical community plays a central role in developing and carrying out interventions to protect and promote women's health.

Inhibition of human brain and RBC acetylcholinesterase (AChE) by heptylphysostigmine (HPTL).

Heptylphysostigmine (HPTL), a derivative of the AChE inhibitor physostigmine (PHY), is under investigation as a therapeutic agent in Alzheimer's disease. HPTL is active against human RBC AChE both in vitro and in vivo. Activity of HPTL against human brain has not been documented. We have developed an in vitro assay system using particulate membrane fractions which permits comparison of inhibition and recovery kinetics of human RBC (primarily globular dimer) and brain (primarily globular tetramer) membrane-bound forms. Under these conditions the HPTLIC50 is similar for the two forms. RBC AChE inhibition spontaneously reverses in 24 h, as occurs in vivo. In striking contrast, activity of inhibited brain enzyme does not recover on overnight incubation. DDVP-induced inhibition, but not HPTL inhibition, can be reversed by the oxime 2-PAM. Some recovery of HPTL inhibition, but not to the level seen with RBC AChE, occurs on addition of heat-stable fractions from serum or CSF. Brain enzyme recovers rapidly from PHY in this system. Responses of brain and RBC AChE to HPTL indicate that these forms are functionally as well as structurally distinct. Since brain inhibition apparently does not spontaneously reverse like RBC inhibition, peripheral measurements of patient responses should be assessed with caution during treatment with HPTL.

Transdermal patch delivery of acetylcholinesterase inhibitors.

Transdermal delivery of cholinesterase inhibitors (ChEI) for treatment of dementia would have advantages associated with continuous dosing and enhanced compliance, but feasibility depends on achieving desired levels of central nervous system enzyme inhibition. We developed a patch technique for assessing delivery of ChEI in rats and examined two organophosphate compounds, metrifonate and DDVP, and a carbamate, heptylphysostigmine, for production of peripheral and central nervous system ChE inhibition at target levels. With DDVP, a log-dose/percent brain AChE inhibition was obtained over a range of 10-65% inhibition within a 10-fold concentration of inhibitor in the patch. Brain cholinesterase was inhibited up to seven days after a 24-h patch application. Long-term inhibition was greater than that attained after intramuscular injection, but without the rapid initial inhibition peak seen with the latter route. In contrast to DDVP, sustained high levels of brain enzyme inhibition could not be produced by transdermal delivery of metrifonate or heptylphysostigmine. Apparently DDVP has features, i.e., liquid state in pure form and high inhibitor potency, which make it particularly suitable for patch administration.

Effects of time and cholinesterase inhibitor treatment on multiple cerebrospinal fluid parameters in Alzheimer's disease.

Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degeneration and as biomarkers of the disease. To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted.

Contact dermatitis in Salvador, Brazil.

In Salvador, Brazil, 536 patients were patch tested with 24 contact allergens. The most common sensitizers included potassium dichromate, thimerosal, hydroquinone, nitrofurazone ointment and nickel sulfate. The results of this South American study are compared with those published by North American and European dermatologists. Low frequencies of positive reactions were encountered in Salvador to some substances, including mercury bichloride and p-phenylenediamine. The influences of climate and life style in determining patterns of contact sensitivity are discussed.

Leishmania mexicana in C3H mice: BCG and levamisole treatment of established infections.

The effect of BCG and levamisole on the course of established murine leishmaniasis was examined. C3H mice infected subcutaneously in the perinasal region with 10(5) L. mexicana promastigotes produced chronic non-ulcerating, non-healing lesions and demonstrated positive humoral and delayed hypersensitivity responses to leishmanial antigens. Infected animals were treated during months 3-5 of infection with either live BCG or with levamisole. Neither treatment resulted in resolution of lesions or in production of a hyperallergic form of infection; similarly, neither immune responses to leishmanial antigens nor histopathological features of lesions were significantly altered. BCG treatment resulted in accelerated growth of primary leishmanial lesions and in the appearance of metastases in some animals. Levamisole treatment of uninfected animals resulted in low levels of antibodies reacting with promastigote antigens, but not in positive delayed intradermal responses. BCG induced delayed intradermal sensitivity to PPD in both infected and control animals; significantly increased delayed reactions to leishmania, were observed in treated uninfected mice.