[Challenges in accessing treatment for chronic hepatitis B in Madagascar : A qualitative study of caregivers and patients]. / Enjeux et difficultés de l'accès aux traitements pour la prise en charge de l'hépatite B chronique à Madagascar : étude qualitative auprès des soignants et personnes atteintes.

OBJECTIVES: Madagascar faces many difficulties in accessing diagnosis and treatment of hepatitis B. The prevalence of chronic hepatitis B infection is estimated at 6.9%. The costs associated with screening and treatment are high and not easily accessible. This article proposes a reflection on the challenges and difficulties of access to diagnosis and treatment for patients with chronic hepatitis B. METHOD: The "Neo Vac" study aimed to document the life paths of people living with chronic hepatitis B, their difficulties and their perceptions of HBV. Twenty-three semi-structured interviews were conducted in 2019 in Antananarivo with patients and gastroenterologists. RESULTS: The study describes the numerous obstacles that mark the therapeutic pathways of chronic HBV patients. The first result indicates lack of knowledge of the disease by chronic HBV patients and the varied circumstances in which the disease is discovered. None of the persons interviewed had been screened on their own initiative, the screening having taken place during prenatal consultations or emergency hospitalizations or during a morbidity episode. The care pathway was characterized by doubt and anxiety due to lack of knowledge about the possible disease outcome and concern about the costs of care. DISCUSSION: Little known by the population and health professionals, hepatitis B is rarely the subject of voluntary screening and is most often detected during an apparently unrelated health event. The exorbitant cost of treatment for patients, the cost of medical analyses and secondary costs, and the unavailability of follow-up tests outside the capital constitute barriers to access to care that are insurmountable for the majority of the Malagasy population. CONCLUSIONS: This first qualitative study on the experiences of HBV-infected persons in terms of access to care and treatment in Madagascar underlines the extent to which access to treatment remains limited, due to the absence of a national policy for the prevention, screening and management of hepatitis B, which remains a highly neglected and unrecognized disease in Madagascar as well as internationally.

Intranasal dopamine treatment reinstates object-place memory in aged rats.

Following oral or IV administration, dopamine (DA) cannot cross the blood-brain barrier to a significant extent, but can enter the brain when administered via the nasal passages. Intranasal administration of DA was shown to increase extracellular DA in the striatum, to have antidepressant action and to improve attention and working memory in rats. Here we show that aged (22-24 months old) rats are deficient in an object-place learning task, but that this learning/memory is intact and comparable with that of adult rats upon pre-trial administration of 0.3 mg/kg DA gel into the nasal passages. This result raises the possibility of the therapeutic application of intranasal DA treatment for age-related cognitive disorders.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.

Intranasal administration of progesterone increases dopaminergic activity in amygdala and neostriatum of male rats.

We evaluated the effects of intranasal administration of progesterone (PROG) on the activity of dopaminergic neurons in the brain of anesthetized rats by means of microdialysis. Male Wistar rats were implanted with guide cannulae in the basolateral amygdala and neostriatum. Three to 5 days later, they were anesthetized with urethane, and dialysis probes were inserted. After a stabilization period of 2 h, four 30-min samples were collected. Thereafter, the treatment (0.5, 1.0 or 2.0 mg/kg of PROG dissolved in a viscous castor oil mixture, or vehicle) was applied into the nose in a volume of 10 microl (5 microl in each nostril). In other animals, an s.c. injection of PROG (1.0, 2.0 or 4.0 mg/kg) or vehicle was given. Samples of both application ways were collected at 30-min interval for 4 h after the treatment and immediately analyzed with high performance liquid chromatography and electrochemical detection. Intranasal administration of 2 mg/kg of PROG led to an immediate (within 30 min after the treatment) significant increase in the basolateral amygdala dopamine levels. In the neostriatum, the 2 mg/kg dose led to a delayed significant increase in dopamine. S.c. administration of 4 mg/kg of PROG was followed by a delayed significant increase in dopamine, both, in the basolateral amygdala and neostriatum, but smaller in magnitude in comparison to the intranasal treatment. This is the first study to demonstrate dopamine-enhancing effects of PROG, not only in the neostriatum, but also in the basolateral amygdala. Our results indicate that the intranasal route of administration of PROG is a more efficacious way for targeting the brain than the s.c. route.

Sleep after intranasal progesterone vs. zolpidem and placebo in postmenopausal women - A randomized, double-blind cross over study.

CONTEXT: The loss of progesterone during menopause is linked to sleep complaints of the affected women. Previously we demonstrated sleep promoting effects of oral progesterone replacement in postmenopausal women. The oral administration of progesterone, however, is compromised by individual differences in bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep-endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in healthy postmenopausal women. DESIGN: This was a randomized double-blind cross-over study. SETTING: German monocentric study PARTICIPANTS: Participants were 12 healthy postmenopausal women. INTERVENTIONS: Subjects received in randomized order four treatments, 2 doses of intranasal progesterone (4.5 mg and 9 mg of MPP22), 10 mg of zolpidem and placebo. OUTCOME MEASURES: Main outcome were conventional and quantitative sleep-EEG variables. Secondary outcomes were the subjective sleep variables and the sleep related concentrations of cortisol, growth hormone (GH), melatonin and progesterone. RESULTS: Sleep promoting effects were found after the higher dosage of MPP22 and after zolpidem. Zolpidem prompted benzodiazepine-like effects on quantitative sleep EEG as expected, whereas no such changes were found after the two dosages of MP22. Nocturnal progesterone levels increased after 9.0 mg MPP22. No other changes of hormone secretion were found. CONCLUSIONS: Our study shows sleep promoting effects after intranasal progesterone. The spectral signature of intranasal progesterone did not resemble the sleep-EEG alterations induced by GABA active compounds. Progesterone levels were elevated after 9.0 mg MPP22. No other endocrine effects were observed.

Sacroplasty versus vertebroplasty: comparable clinical outcomes for the treatment of fracture-related pain.

BACKGROUND AND PURPOSE: Little is known about the long-term clinical outcomes of sacroplasty, a relatively new minimally invasive percutaneous procedure for the treatment of sacral insufficiency fractures. The first purpose of the present study, therefore, was to investigate the effects of sacroplasty on pain, mobility, and activities of daily living (ADLs). A second purpose was to compare clinical outcomes of sacroplasty with those of vertebroplasty, a similar but more established procedure. MATERIALS AND METHODS: A retrospective case series of 12 patients who had a sacroplasty and a control group of 21 patients who had undergone a vertebroplasty was conducted. A 12-item questionnaire and subsequent telephone interview requested each patient to rate the intensity of pain, as well as the ability to ambulate and perform ADLs, before sacroplasty or vertebroplasty, and at the time of the interview. RESULTS: There was a statistically significant decrease in overall self-reported pain, as well as an increase in self-reported ability to ambulate and perform ADLs after sacroplasty or vertebroplasty. These improvements were equivalent, regardless of which procedure the patient received. CONCLUSION: The present study suggests that the treatment of sacral insufficiency fractures with sacroplasty produces relatively long-lasting improvements in pain, mobility, and the ability to perform ADLs. These data also suggest that the clinical outcomes of sacroplasty are comparable with those of vertebroplasty, an accepted and more routinely performed procedure.

Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat.

Here we assessed the effects of i.g. administration of Zingicomb (ZC), a mixture of zingiber officinale and ginkgo biloba extracts, on learning and memory, and on indicators of oxidative stress in aged rats. Effects of ZC (1 and 10 mg/kg) were investigated in 22-24 months old Wistar rats using the Morris water maze, in which they show deficient performance as compared to 3 months old rats in the undrugged state (days 1 and 2). Treatment was administered on days 3 and 4 of training, then over 7 days with training discontinued, and again on days 5 and 6 when training was resumed. Thereafter chronic treatment was maintained over 5 months. 1 mg/kg ZC improved escape learning in the water maze. The two capital indicators of oxidative stress in brain homogenates, the amount of oxidized proteins (assessed as carbonyl group containing proteins) and lipid peroxidation, were significantly reduced in ZC treated animals. Thus, ZC, which had previously been shown to improve inhibitory avoidance learning and to have anxiolytic properties in adult animals, might also facilitate spatial learning in aged animals, and reduces indices of oxidative stress in brain tissue after chronic treatment.

The distribution of acetylcholinesterase in buds of the rat vallate papilla as determined by electron microscope histochemistry.

The distribution of acetylcholinesterase (AChE) in the rat vallate papillary bud was investigated by histochemical electron microscopy. Previous reports of specific AChE activity around subgemmal and intragemmal nerves and between some taste bud cells have been confirmed. In addition we have consistently observed dense precipitation between microvilli in the taste pore. The studies suggest that the neurotransmitter, acetylcholine, may be involved in early events in the taste process which are believed to occur in the pore.

Localization of human immunodeficiency virus core antigen in term human placentas.

Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental amebiasis. I. Pathogenicity of axenically cultured Entamoeba histolytica in the brain of the newborn mouse.

Axenically cultured Entamoeba histolytica inoculated intracerebrally into newborn Swiss mice invaded the cerebrum and produced multiple abscesses containing viable trophozoites. As few as 20 amebae of a virulent strain (HM-1:IMSS) occasionally produced fatal disease, 200 killed about 75% of animals and higher doses regularly killed all animals. In contrast, avirulent strains (HK-9 and HB-301:NIH) failed to produce acute brain disease in comparable time periods even when mice were inoculated with as many as 20,000 amebae. Two other strains (1295 and H-458:CDC) were of intermediate virulence. High doses of avirulent amebae often produced hydrocephalus as a late manifestation. In newborn, 3 week-old, and 6-week-old mice resistance to infection increased with age, and older animals often responded late to virulent strains by developing hydrocephalus.

Experimental amebiasis. II. Hepatic amebiasis in the newborn hamster.

Newborn hamsters inoculated intrahepatically were highly susceptible to infection by axenically cultured Entamoeba histolytica. Inoculations were performed through the abdominal wall, and lesions could be observed through the skin as early as 4 days after inoculation. The most virulent amebal strain, HM-1:IMSS, produced liver lesions in 19% of newborn animals inoculated with 20 amebae, and in about 90% receiving 2,000 amebae. Eleven other strains similarly tested either produced no lesions with 20,000 amebae or were of intermediate virulence. Two hamster strains did not show appreciable differences in susceptibility to the HM-1:IMSS amebal strain. Newborn hamsters were more susceptible to HM-1:IMSS amebae than animals which were 2, 4, or 7 days old at the time of inoculation. Three-week-old animals were resistant to doses below 20,000 virulent amebae.

Lectin and toxin-like activities of Entamoeba histolytica: comparison of properties.

A comparison was made between properties of a recently discovered Entamoeba histolytica lectin which has a carbohydrate specificity for N-acetylglucosamine oligosaccharides and the previously found toxin-like principle of the ameba. A separation between these two activities was achieved upon subcellular fractionation by high speed centrifugation of freeze-thawed disrupted E. histolytica trophozoites (strain HM-1). Practically all of this lectin activity, as determined by hemagglutination of glutaraldehyde-fixed human erythrocytes, was found associated with the sedimented membrane fraction. This fraction did not affect monolayers of tissue-cultured mammalian cells. On the other hand, the soluble supernatant solution caused extensive damage to the tissue-cultured cells (change in morphology and detachment of cells). Both the lectin and toxin activities were heat-labile and their activities were preserved by the presence of reducing agents and proteolytic enzyme inhibitors. In contrast to the toxin, the isolated lectin was inactive at pH 7.2 and active only at pH 5.7-6.0. Both the lectin and toxin were inhibited by a number of macromolecular compounds such as chitin, peptidoglycan, bovine serum and an IgA fraction isolated from human colostrum. Only the lectin activity, however, was inhibited by low molecular weight chitin oligosaccharides (GlcNAc)n=2-6 or by lysozyme-digested peptidoglycan subunits. Moreover, fetuin and a ganglioside mixture extracted from ox brain were found to inhibit only the toxin-like activity. The IgG fraction of sera from patients with invasive amebiasis neutralized both lectin and toxin-like activities, while IgG from normal sera failed to neutralize either activity. Although our results indicate that in E. histolytica, lectin and toxin are two separate activities, both of them share a considerable number of properties which does not exclude the possibility that they may be related.

Experimental amebiasis. IV. Amebal viruses and the virulence of Entamoeba histolytica.

We have attempted to determine whether amebal viruses are capable of viral conversion of the virulence of Entamoeba histolytical. Amebae of little or no virulence for the newborn hamster liver were infected with viruses obtained from four amebal strains of different virulence. Cultures of surviving amebae were increased in virulence by viruses from amebae of high, moderate, or low virulence, but decreased in virulence by the virus of the second most pathogenic amebal strain. Sequential infection with two viruses did not produce consistent cumulative effects on virulence. The changes in virulence noted are considered to be the unpredictable result of either selection pressures exerted by the lytic virus infection or possibly viral alterations of the amebae.

Experimental amebiasis. III. A rapid in vitro assay for virulence of Entamoeba histolytica.

A rapid and simple assay for cytopathogenicity of axenically cultivated Entamoeba histolytica has been developed employing baby hamster kidney (BHK) or mouse 3T3 cells conventionally tissue cultured. Three of the twelve amebal strains tested produced total destruction of the BHK cell monolayer in 2--3 hours, and these three strains are the three most virulent strains for the newborn hamster liver. Two additional strains were of moderate cytopathogenicity in vitro and of moderate virulence in vivo. Seven strains were of low cytopathogenicity and virulence. Within these three major groupings, however, the cytopathogenicity ranking was not entirely reproducible. The general correspondence of cytopathogenicity in vitro and virulence in vivo and the possibility of obtaining data within a few hours suggest such an assay may prove a useful tool in amebiasis research.

Entamoeba histolytica "toxin": fetuin neutralizable and lectin-like.

Extracts of Entamoeba histolytica produce rounding and agglutination of mammalian cells in tissue culture. This effect is inhibited or reversed by serum, by the serum glycoprotein, fetuin, or by N-acetyl-D-galactosamine. Concanavalin A produces a similar cytotoxic effect that is blocked or reversed by alpha-methyl mannoside. These properties suggest that the amebal "toxin" has a lectin-like activity.

Transdermal fentanyl in opioid-naive cancer pain patients: an open trial using transdermal fentanyl for the treatment of chronic cancer pain in opioid-naive patients and a group using codeine.

To treat cancer pain, physicians often decide to jump directly from step 1 of the World Health Organization (WHO) analgesic ladder to step 3. The use of transdermal fentanyl in patients with cancer pain who had either used no opioid before, or only codeine, is evaluated in the present trial. Both opioid-naive (N = 14) and codeine-using (N = 14) patients started with transdermal fentanyl in the lowest available delivery rate (25 microg/hr). Immediate-release oral morphine was present as "rescue" medication. Transdermal fentanyl provided good to excellent pain relief in the majority (68%) of these patients. During the study, 5 patients continued with 25 microg/hr, and the others used a higher dose. Clinically relevant respiratory depression was not observed. The common side effects of opioids were found; constipation was mentioned by 3 patients (11%). Transdermal fentanyl appeared a safe analgesic in these opioid-naive cancer pain patients. In this study, WHO step 2 could be skipped without untoward complications.

The treatment of chronic cancer pain in a cancer hospital in The Netherlands.

In a prospective study of 313 Dutch cancer patients with chronic pain, the practice of pain treatment was evaluated by means of Donabedian's structure-process-outcome framework. The practice of pain treatment was assessed by: (1) structural resources, describing the setting in which pain treatment is provided; (2) process components, which describe the clinical practice; and (3) outcome measures, which refer to patients' pain intensity, patient satisfaction, or composite pain management index scores. Results showed that 31.4-59.8% of the cancer pain patients received less than optimal pain treatment. Although pain education and refresher courses for health care providers are scarce, structural resources were not the major cause of the suboptimal level of pain treatment. Rather, the major cause was the process components. Only 36.4% of the patients received strong opioids; 23.1% received analgesics "as needed." Patients' pain knowledge was far from optimal (54.8 on a 0-100 scale), and written pain information was given to only 15.8% of the patients. After discharge, only 36.8% of the district nurses were informed about patients' pain. These results emphasize that continuing efforts to improve the practice of pain treatment are needed.

Blockade of lithium chloride-induced conditioned place aversion as a test for antiemetic agents: comparison of metoclopramide with combined extracts of Zingiber officinale and Ginkgo biloba.

The present study tests the hypothesis that the blockade of lithium chloride-induced conditioned place aversion might be a suitable model to assess antiemetic properties of drugs, especially in species that do not vomit, like rats. The effects of the known antiemetic compound metoclopramide were compared with those of zingicomb, a combination preparation of extracts of Ginkgo biloba and Zingiber officinale, also presumed to have antiemetic properties. Place conditioning was performed using a conventional three-compartment test procedure. On three successive conditioning trials, rats received an intraperitoneal (i.p.) injection of lithium chloride (125 mg/kg) and were placed into the compartment that they had preferred over three baseline trials. During the test, rats treated with lithium chloride (LiCl) spent less time in the treatment compartment, indicative of a conditioned place aversion (CPA). In the first experiment, metoclopramide (MCP) was administered intragastrically (IG) in doses of 2 or 10 mg/kg 60 min prior to LiCl injection. The pretreatment with 50 and 100 mg/kg zingicomb attenuated the LiCl-produced CPA, whereas a dosage of 10 mg/kg had no effect. These findings suggest that LiCl-induced CPA is a viable procedure with which to assess the antiemetic properties of metoclopramide. Furthermore, the data confirm the hypothesis that the phytopharmacon zingicomb might have antiemetic properties that are comparable to those of metoclopramide.