Factors associated with local herb use during pregnancy and labor among women in Kigoma region, Tanzania, 2014-2016.

BACKGROUND: Despite research suggesting an association between certain herb use during pregnancy and delivery and postnatal complications, herbs are still commonly used among pregnant women in sub-Sahara Africa (SSA). This study examines the factors and characteristics of women using local herbs during pregnancy and/or labor, and the associations between local herb use and postnatal complications in Kigoma, Tanzania. METHODS: We analyzed data from the 2016 Kigoma Tanzania Reproductive Health Survey (RHS), a regionally representative, population-based survey of reproductive age women (15-49 years). We included information on each woman's most recent pregnancy resulting in a live birth during January 2014-September 2016. We calculated weighted prevalence estimates and used multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with use of local herbs during pregnancy and/or labor, as well as factors associated with postnatal complications. RESULTS: Of 3530 women, 10.9% (CI: 9.0-13.1) used local herbs during their last pregnancy and/or labor resulting in live birth. The most common reasons for taking local herbs included stomach pain (42.9%) and for the health of the child (25.5%). Adjusted odds of local herb use was higher for women reporting a home versus facility-based delivery (aOR: 1.6, CI: 1.1-2.2), having one versus three or more prior live births (aOR: 1.8, CI: 1.4-2.4), and having a household income in the lowest versus the highest wealth tercile (aOR: 1.4, CI: 1.1-1.9). Adjusted odds of postnatal complications were higher among women who used local herbs versus those who did not (aOR: 1.5, CI: 1.2-1.9), had four or more antenatal care visits versus fewer (aOR: 1.4, CI: 1.2-1.2), and were aged 25-34 (aOR: 1.1, CI: 1.0-1.3) and 35-49 (aOR: 1.3, CI: 1.0-1.6) versus < 25 years. CONCLUSIONS: About one in ten women in Kigoma used local herbs during their most recent pregnancy and/or labor and had a high risk of postnatal complications. Health providers may consider screening pregnant women for herb use during antenatal and delivery care as well as provide information about any known risks of complications from herb use.

Thyroid antibodies are associated with stenotic lesions in the terminal portion of the internal carotid artery.

BACKGROUND AND PURPOSE: Several studies have reported moyamoya syndrome associated with thyroid disease, and the mechanism involved in this relationship is unknown. This study aimed to clarify the involvement of thyroid antibodies and thyroid function in intracranial arterial stenosis. METHODS: The study included 30 patients <65 years of age with intracranial arterial steno-occlusion. Patients with definitive moyamoya disease were excluded. Thyroid function and thyroid antibody levels were evaluated. The steno-occlusive site and the presence of moyamoya vessels were evaluated using digital subtraction angiography. The characteristics of intracranial arterial lesions were compared between patients with and without elevated thyroid antibody levels, and between patients with increased thyroid function and those with normal thyroid function. RESULTS: Five patients had increased thyroid function and seven had elevated thyroid antibody levels. Four were diagnosed with Graves' disease, 13 with atherosclerotic intracranial stenosis, two with intracranial arterial dissection, one with vasculitis syndrome and 10 with intracranial stenosis of unknown cause. All patients with Graves' disease and patients with elevated antithyroid peroxidase antibody levels had steno-occlusion in the terminal portion of the internal carotid arteries, whereas most of the patients with normal thyroid function or without elevated thyroid antibody levels had stenosis in the middle cerebral arteries. CONCLUSIONS: In young and middle-aged patients, a lesion in the terminal portion of the internal carotid artery was associated with elevated thyroid antibody levels and increased thyroid function. Stenoses found in the terminal portion of the internal carotid artery and immune-mediated thyroid diseases may share a common background.

Comparisons of the prevalence of and risk factors for elderly depression between urban and rural populations in Japan.

BACKGROUND: The aim of the present study was to investigate the differences in the prevalence of and risk factors for elderly depression between urban and rural areas in Japan and to further understanding of the features of elderly depression. METHODS: A multistage, random sampling procedure and mailing method were used in urban and rural areas in Kumamoto Prefecture. A total of 2,152 participants aged 65 years and older were evaluated for depression using the Geriatric Depression Scale (GDS). Factors associated with depression were also examined. In order to assess the relationship between risk factors and subjective happiness, the Philadelphia Geriatric Center Morale Scale (PGC-MS) was used. RESULTS: Depressive symptoms were associated with living alone, being unemployed, chronic illness, sleep disturbance, suicidal ideation, financial strain, and poor social support; the risk factors for elderly depression were almost the same in the two areas. Although three factors (financial strain, work status, and PGC-MS) were significantly associated with depression in both areas on logistic regression analysis, sleep disturbance was significant only for the urban area, and poor social support was significant only for the rural area. CONCLUSIONS: Although factors related to depression did not differ markedly between urban and rural elderly people, some risk factors differed between the two areas. Effective intervention programs for elderly depression should pay more attention to regional differences.

Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture.

We are interested to know whether expression of a lineage-specific growth factor receptor is deterministic to lineage commitment during hematopoiesis. For this purpose, we introduced the human c-fms gene into the multipotential stem cell clone LyD9 and two myeloid progenitor clones, L-GM3 and L-G3, cells that differentiate in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF, respectively. Although LyD9 cells have differentiation potential to become macrophages, c-fms transfectants of LyD9 and L-GM3 cells did not differentiate in response to human macrophage (M)-CSF. However, c-fms transfectants of L-G3 cells differentiated to neutrophils in response to human M-CSF. These results indicate that the M-CSF receptor requires a specific signal transduction pathway to exert its differentiational and proliferative effects. Furthermore, the M-CSF receptor can convey a granulocyte-type differentiation signal possibly by cooperating with the G-CSF receptor signal transduction pathway. The c-fms-transfected LyD9 cells as well as the original LyD9 cells differentiated predominantly into GM-CSF- and G-CSF-responsive cells by coculturing with PA6 and ST2 stromal cells, respectively. The results indicate that differentiation lineage is not affected by premature expression of the M-CSF receptor. Instead, the stromal cell used for coculture apparently controls lineage-selective differentiation of the multi-potential stem cell line.

Rational design of potent antagonists to the human growth hormone receptor.

A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially--a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.

Hyperthermia-induced neuronal protection against ischemic injury in gerbils.

We investigated the effect of hyperthermic pretreatment before induction of ischemia using a gerbil model of 5-min forebrain ischemia. A single hyperthermic treatment 18 h before ischemia exhibited a partial protective effect, and repetitive hyperthermic pretreatments at 18-h intervals before ischemia showed clear protection against neuronal death in the CA1 area of the hippocampus, whereas single hyperthermic treatment 3, 6, 24, or 50 h before ischemia exhibited little protective effect. This transient and cumulative neuroprotective effect of hyperthermic pretreatment strongly suggested the involvement of stress reactions after hyperthermia in the protective mechanism against ischemic neuronal death.

Silent brain infarction and coronary artery disease in Japanese patients.

OBJECTIVE: Silent brain infarction is fairly common in the elderly, but predictive factors have not been definitively established. This study focuses attention on ischemic heart disease and cerebrovascular risk factors about the frequency of silent brain infarction. DESIGN: The existence of silent brain infarction, the extent of coronary artery stenosis, and cerebrovascular risk factors of consecutive 92 case series with suspected ischemic heart disease were surveyed. SETTING: A hospital for patients with ischemic heart disease. PATIENTS: Ninety-two consecutive Japanese patients with suspected ischemic heart disease were recruited. MAIN OUTCOME MEASURES: All subjects were evaluated for coronary atherosclerosis (number of coronary arteries with significant stenosis and Gensini score), the number of silent brain infarctions detected by computed tomography, the extent of carotid atherosclerosis as determined by B-mode ultrasonography, and cerebrovascular risk factors. RESULTS: Patients with silent cerebral infarctions were older (66.2 +/- 10.4 years) than those without such events (60.1 +/- 8.8 years) (P < .01). The extent of coronary atherosclerosis in patients with silent cerebral infarctions was significantly greater than in those without such events after adjustment for the effect of age (P < .001). The extent of carotid atherosclerosis and the percentages of individuals with hypertension, diabetes mellitus, a smoking habit, hypercholesterolemia, hypertriglyceridemia, and a low serum high-density lipoprotein cholesterol level did not differ between the groups with and without silent brain infarction. The frequency of silent brain infarction increased with the severity of coronary stenosis. CONCLUSION: Coronary atherosclerosis and age were important risk factors for silent brain infarction.

Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage--immunohistochemical investigation of dendritic damage.

We investigated the neuronal distribution of microtubule-associated protein 2 in gerbil brain and monitored the progression of ischemic damage immunohistochemically by using this protein as a dendritic marker. The reaction for microtubule-associated protein 2 in normal gerbil brain clearly visualized neuronal soma and dendrites but other structures such as axonal bundles, glia and endothelial cells exhibited little immunoreactivity. In a reproducible gerbil model of unilateral cerebral ischemia, we could detect the ischemic lesions as early as 3 min after right common carotid occlusion at the subiculum-CA1 region of the ipsilateral hippocampus as faint loss of the reaction in the dendrites. After ischemia for 30 min, the ischemic lesions were clearly detected as loss of the reaction in the nerve cell bodies, dendrites and the neuropil in the hippocampus, cerebral cortex, thalamus and the caudoputamen. Although the mechanism for prompt disappearance of the immunohistochemical reaction for microtubule-associated protein 2 is not clear, the present investigation suggests that dendrites in the vulnerable regions may be quite susceptible to ischemic stress and that the immunohistochemical procedure for microtubule-associated protein 2 may be very useful for demonstration of dendritic damage in various pathophysiological states of the central nervous system.

Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death.

We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.

Structure and expression of a cloned cDNA for human (2'-5')oligoadenylate synthetase.

17S poly(A)+RNA, which hybridized to an oligonucleotide complementary to a part of the partial cDNA (E1cDNA) (Merlin et al. (1983) Proc. Natl. Acad. Sci. U.S. 80, 4904) for 2-5A synthetase, was isolated from interferon-treated human KB cells and used for cDNA cloning. Several overlapping cDNAs were cloned by using the oligonucleotide as a probe. Two of them were joined at their overlapping region, resulting in a cDNA (22-1 cDNA) of 1.4 kb containing a long open reading frame. When the cDNA was expressed in COS-7 cells with an eukaryotic promoter, active 2-5A synthetase was produced and localized mainly in the cytoplasm. The 5'-proximal ATG in 22-1 cDNA is followed immediately by another ATG. This second ATG was assumed to work as the initiator codon. If so, this enzyme comprises 363 amino acids.

Purification, crystallization, and molecular properties of aspartase from Pseudomonas fluorescens.

Aspartase [L-aspartate ammonia-lyase, EC 4.3.1.1] of Pseudomonas fluorescens was highly purified to homogeneity and crystallized. The purified enzyme sedimented as a monodisperse entity upon ultracentrifugation with a s0(20),w value of 8.6S. Upon polyacrylamide gel electrophoresis (PAGE), the enzyme migrated as a single band. The molecular weight of the native enzyme was 173,000 +/- 3,000, as determined by sedimentation equilibrium analysis, and that of the enzyme subunit was determined to be 50,000 +/- 1,500 by sodium dodecyl sulfate (SDS)-PAGE. Cross-linking experiments using dimethyl suberimidate followed by SDS-PAGE indicated that the native enzyme was composed of four subunits with identical molecular weight. The amino acid composition of the enzyme was determined.

In vivo hypoxia-induced neuronal damage in dentate gyrus of rat hippocampus: changes in NMDA receptors and the effect of MK-801.

Hypoxia is a major cause of ischaemia-induced neuronal damage. In the present study, we examined the effects of in vivo hypoxia on N-methyl-D-aspartate receptors (NMDAR) in the rat hippocampus. This model of in vivo hypoxia involved placing rats in a hypoxic chamber containing 5% O2 and 95% N2 for 30 min. In the hippocampus, neuronal cells in the CA3, the hilus of the dentate gyrus and the dentate gyrus (DG) were damaged. In the CA1, which is known to be vulnerable to ischaemic damage, neuronal cells did not show hypoxia-induced damage. In vivo hypoxia-induced damage caused morphological changes in neuronal cells, such as shrunken, spindle or triangular shapes accompanied by pyknotic nuclei, but did not induce the loss of neuronal cells. On the other hand, the number of binding sites for [3H]-1-[1-(2-thienyl)cyclohexyl]-3,4-piperidine hydrochloride (TCP) gradually decreased on and after 7 days, and then maximally decreased by 25% at 21 days after hypoxia. The number of NMDAR1-immunopositive cells was decreased by 22% in the DG, but was unchanged in the CA3. Furthermore, we examined the effect of a non-competitive NMDA antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,b] cyclohepten-5,10-imine hydrogen maleate (MK-801), on against in vivo hypoxia. The administration of MK-801 (3 mg/kg, i.p.), 30 min before hypoxia treatment, partly protected against neuronal damage in the DG, but not in the CA3. These results suggest that hypoxia-induced neuronal damage in the DG involves, in part, the activation of NMDAR.

Delayed expression of c-fos protein in rat hippocampus and cerebral cortex following transient in vivo exposure to hypoxia.

The time course of c-fos protein expression after hypoxia was examined in rat hippocampus and cerebral cortex using an immunohistochemical method. The rats were exposed to in vivo hypoxia for 30 min in a chamber containing 5% O2 and 95% N2. Immediately after the treatment, c-fos protein-like immunoreactivity was observed in the granule cell layer of the dentate gyrus. The change was transient, and the density of immunoreactive cells returned quickly to a control level 3 h after the exposure. However, the density of positive cells was again increased 1 day after hypoxia and reached the maximum 7 days after. In the cerebral cortex, on the other hand, no change was detected in the pattern of staining at any time, with an exception on 21 days after hypoxia. At this period, positively stained neurons were significantly increased in both density and intensity throughout the entire extent of the cerebral cortex including the cingulate gyrus. These results clearly indicate that hypoxia induces different patterns of c-fos protein expression among various regions of the brain. The biphasic pattern seen in the dentate gyrus as well as the delayed expression in the cerebral cortex may be related to delayed neuronal damages induced by hypoxia.

Role of prostacyclin in the response of cerebral blood flow to CO2.

The prostacyclin (PGI2) formation in cerebral vessels, as reflected by the difference in concentration of internal carotid arterial and internal jugular venous radioimmunoassayed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), was determined under normocapnic and hypercapnic conditions in 5 patients with mild cerebral thrombotic infarction. There was no evidence that endogenous PGI formation in cerebral vessels was stimulated at mild hypercapnia, while an increase of cerebral blood flow (CBF) induced by hypercapnia was observed. These results suggest that endogenous PGI2 may not be a mediator for the response of CBF to CO2.

Prediction of stroke-prone gerbils and their cerebral circulation.

We attempted to predict the severity of cerebral ischemia, prior to permanent occlusion of a common carotid artery (CCA), in the gerbil by measuring the diameter of the distal CCA before and during temporary ligation and correlated the severity of cerebral ischemia and the pattern of cerebral circulation. All gerbils with reduction of the diameter over 44% after temporary occlusion developed severe neurological signs following permanent ligation. These gerbils lacked any connection between the left and right anterior cerebral arteries (ACA) and the pericallosal arteries originated from the ACA of the occluded side. No gerbils with reduction of less than 30% developed neurological signs and those gerbils possessed a definite anastomosis between the ACAs from both sides. Six of 7 gerbils without connection between the ACAs whose pericallosal arteries originated from the ACA of the non-occluded side proved to be moderately symptomatic. It was concluded that we could reliably predict severely symptomatic and moderately symptomatic gerbils with specific cerebral circulation patterns prior to permanent occlusion of the CCA. The preselected 'stroke-prone' gerbils should be useful for the investigation of cerebral ischemia and the evaluation of pharmacological agents.

Cerebral ischemic response-like hemodynamic changes induced by telencephalic ischemia in Mongolian gerbils (Meriones unguiculatus).

The effect of bilateral common carotid occlusion on systemic hemodynamics was investigated in the gerbil with and without bilateral carotid sinus denervation. Irrespective of the sinus denervation, telencephalic, severe ischemia produced significant changes in the heart rate and systemic arterial blood pressure, similar to those observed in cerebral ischemic response. These hemodynamic changes, associated with cerebral ischemia, may play an important role in affecting the pathophysiology of cerebral ischemia itself.

'Ischemic tolerance' phenomenon found in the brain.

We investigated the possibility that neuronal cells given a mild ischemic treatment sufficient to perturb the cellular metabolism acquired tolerance to a subsequent, and what would be lethal, ischemic stress in vivo. Cerebral ischemia was produced in the gerbils by occlusion of both common carotids for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. Minor 2-min ischemia in this model depletes high-energy phosphate compounds and perturbs the protein synthesis, but never causes neuronal necrosis, and therefore was chosen as mild ischemic treatment. Single 2-min ischemia 1 day or 2 days before 5 min ischemia exhibited only partial protective effects against delayed neuronal death. However, two 2-min ischemic treatments at 1 day intervals 2 days before 5 min ischemia exhibited drastically complete protection against neuronal death. The duration and intervals of ischemic treatment, enough to perturb cellular metabolism and cause protein synthesis, were needed respectively, because neither 1-min ischemia nor 2-min ischemia received twice at short intervals exhibited protective effects. This 'ischemic tolerance' phenomenon induced by ischemic stress--which is unquestionably important--and frequent stress in clinical medicine, is intriguing and may open a new approach to investigate the pathophysiology of ischemic neuronal damage.

Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia.

The effects of hypoxia on protein kinase C (PKC) isozymes (alpha, beta I, beta II, and gamma) were examined in the hippocampus from rats subjected to hypoxic conditions (5% O2 in 95% N2) for 30 min in a chamber. Western blot analysis revealed that the total amounts of PKC-alpha (-26.0% of control) and -gamma (-32.7% of control) were decreased significantly at the end of hypoxia, which was followed by the reduction of that of PKC-beta II (-23.7% of control at 7 days after hypoxia). Whereas, the PKC activities, which were measured by the incorporation of [gamma-32P] into a specific PKC substrate peptide, in both the cytosolic and the particulate fractions did not change. The reductions of PKC-gamma and -alpha at the end of hypoxia may be related to the following neuronal degeneration.

Acetazolamide challenge for three-dimensional time-of-flight MR angiography of the brain.

PURPOSE: We compared three-dimensional time-of-flight MR angiograms obtained before and after acetazolamide administration to evaluate whether use of this drug could improve visualization of small peripheral intracranial arteries and atherosclerotic stenosis. METHODS: For evaluation of small peripheral arteries, 10 patients with clinical diagnosis of ischemic cerebrovascular disease and 10 healthy volunteers were investigated, and for evaluation of stenosis, another 6 patients were investigated. Vascular images were obtained by three-dimensional time-of-flight MR angiography. After a baseline scan, 17 mg/kg acetazolamide was injected intravenously and the second scan was performed 20 minutes later. RESULTS: Several small peripheral arteries that had not been seen on the baseline images were visible on the acetazolamide images without any augmentation of the background signals. Stenotic lesions in the main trunks of the major cerebral arteries were detected more clearly on acetazolamide images. CONCLUSIONS: Acetazolamide improves visualization of small peripheral intracranial arteries and sensitivity in detecting atherosclerotic stenosis in the main trunk of major cerebral artery by three-dimensional time-of-flight MR angiography without changing MR apparatus and software.