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M Sasa

Publications and source records attributed to M Sasa.

At least 19 recordsLinked to original sources
PubMed2005

Pan-African polyspecific antivenom produced by caprylic acid purification of horse IgG: an alternative to the antivenom crisis in Africa.

A polyspecific Pan-African antivenom has been produced from the plasma of horses immunized with a mixture of the venoms of Echis ocellatus, Bitis arietans and Naja nigricollis, the three most medically important snakes in sub-Saharan Africa. The antivenom is a whole IgG preparation, obtained by caprylic acid precipitation of non-IgG plasma proteins. The antivenom effectively neutralizes the most important toxic activities of the three venoms used in the immunization in standard assays involving preincubation of venom and antivenom before testing. This antivenom compares favourably with other antivenoms designed for use in Africa with respect to neutralization of the toxins present in the venom of E. ocellatus. Caprylic acid fractionation of horse hyperimmune plasma is a simple, convenient and cheap protocol for the manufacture of high quality whole IgG antivenoms. It constitutes a potentially valuable technology for the alleviation of the critical shortage of antivenom in Africa.

Animals↗
PubMed2001

Inhibitory effects of tandospirone, a 5-HT1A agonist, on medial vestibular nucleus neurons responding to lateral roll tilt stimulation in rats.

An electrophysiological study was performed using chloral hydrate-anesthetized rats to determine whether tandospirone, a 5-HT1A agonist, affects neuronal activities of the medial vestibular nucleus (MVN), since serotonergic innervation and 5-HT1A receptors are present in this nucleus. Tandospirone applied microiontophoretically at a current of 20-60 nA caused an inhibition of tilt-induced firing of alpha-type neurons, which showed increased and decreased firing with lateral tilt ipsilateral and contralateral to the recording site, respectively, along with that of beta-type neurons which exhibited the reverse responses to ipsilateral and contralateral tilt stimulation. The inhibition was antagonized during simultaneous, iontophoretic application of WAY-100635 (20-60 nA), a 5-HT1A receptor antagonist, although WAY-100635 alone rarely affected spontaneous or tilt-induced firing in either type of neurons. These results suggest that tandospirone acts on a 5-HT1A receptor to inhibit transmission of otolith information to alpha- and beta-type MVN neurons.

Action Potentials↗
PubMed2001

Enhanced Ca(2+) influx with mossy fiber stimulation in hippocampal CA3 neurons of spontaneously epileptic rats.

This study was performed to determine whether the intracellular Ca(2+) concentration ([Ca(2+)](i)) is increased in hippocampal CA3 neurons of spontaneously epileptic rats (SER) which show both absence-like and convulsive seizures using hippocampal slices loaded with Calcium Green-1 when a weak single stimulation is given to the mossy fiber. [Ca(2+)](i) in the CA3 area was significantly increased after a single stimulus to mossy fibers in SER, while no changes were detected in normal Wistar rats. These findings suggest the existence of an abnormality in the Ca(2+) channel in the SER CA3 region and that this is probably responsible for epileptic seizures.

Action Potentials↗
PubMed2001

Potentiation of 5-HT(3) receptor functions in the hippocampal CA1 region of rats following repeated electroconvulsive shock treatments.

Modulation of serotonin (5-HT)(3)-receptor function by repeated electroconvulsive shock (ECS) treatment was investigated to elucidate the mechanism underlying the effectiveness of electroconvulsive therapy (ECT) which is clinically used for drug-resistant depression. ECS (100 V, 1 s) was applied once a day for 14 days via an electrode placed on the ears of rats (ECS group). For controls, rats were handled similar to the ECS-treated group except for the stimulation. Hippocampal slices (thickness, 450 microm) were prepared 24 h after the final ECS treatment when rats were 5-6 weeks old. Intracellular recordings were made from the neurons in the CA1 pyramidal cell layer. Activation of 5-HT(3) receptors increased spontaneous postsynaptic potentials (sPSP). Increased sPSP was mainly mediated by GABA. The 5-HT(3) receptor mediated increase in sPSP was potentiated in the ECS group compared with the control group. These findings suggest that the 5-HT(3) receptor function is potentiated by repeated ECS.

Action Potentials↗
PubMed2001

Effect of JTH-601, a putative alpha(1L)-adrenoceptor antagonist, on guinea pig nasal mucosa vasculature.

The existence of alpha(1)-adrenoceptors with low affinity for prazosin, an alpha(1L) subtype, has been proposed in addition to alpha(1)-adrenoceptor subtypes with high affinity for prazosin, i.e. the alpha(1H) group: alpha(1A), alpha(1B) and alpha(1D) subtypes. In the present study, we investigated the effect of JTH-601 (3-(N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminomethyl)-4-methoxy-2,5,6-trimethylphenol hemifumarate), a putative alpha(1L)-adrenoceptor antagonist, on the isolated guinea pig nasal mucosa vasculature. JTH-601 (0.01-0.03 microM) competitively antagonized the noradrenaline-induced contraction of the tissue in a concentration-dependent manner. The pA(2) value for JTH-601 was 8.14 +/- 0.04 (means +/- SEM, n = 6). The data suggests that the alpha(1L)-subtype is involved in the noradrenaline-induced contraction of the guinea pig nasal mucosa vasculature.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Inhibition by L-3,4-dihydroxyphenylalanine of hippocampal CA1 neurons with facilitation of noradrenaline and gamma-aminobutyric acid release.

Electrophysiological studies were performed to elucidate whether L-3,4-dihydroxyphenylalanine (L-DOPA) acted on hippocampal CA1 neurons, since this drug has been reported to act as a neurotransmitter in the hypothalamus and striatum. Hippocampal slices (450 microM thick) obtained from male Wistar rats (4-7 weeks of age) were placed in a bath (maintained at 30+/-1 degrees C) continuously perfused with artificial cerebrospinal fluid. The population spikes elicited by electrical stimuli applied to the Schaffer collateral/commissural fibers were recorded in the hippocampal CA1 region, using a glass micropipette filled with 3 M NaCl. Drugs were applied in the bath through a perfusion system. The population spikes were inhibited by L-DOPA (1 nM-10 microM) with a bell-shaped concentration-response curve (n=7-15). Maximum inhibitory effects were obtained at 100 nM. L-DOPA cyclohexyl ester, a putative L-DOPA recognition site antagonist, antagonized the L-DOPA-induced inhibition of population spike. However, the inhibition remained unaffected in the presence of 3-hydroxybenzylhydrazine, an aromatic amino acid decarboxylase inhibitor. Furthermore, bath application of either phentolamine, an alpha-adrenoceptor antagonist, or bicuculline, a GABA(A) receptor antagonist, antagonized the inhibitory effects of L-DOPA on population spikes. In addition, bicuculline (1 microM) antagonized the inhibition of population spike induced by 6-fluoronorepinephrine (10 microM), an alpha-adrenoceptor agonist, while phentolamine (10 microM) did not affect the muscimol (1 microM)-induced inhibition. These results suggested that L-DOPA itself acted on L-DOPA recognition sites to release noradrenaline, and that the latter facilitates gamma-aminobutyric acid (GABA) release via alpha-adrenoceptors located on the GABA-containing cells and/or their nerve terminals, thereby inhibiting the population spikes in the hippocampal CA1 field.

Action Potentials↗
PubMed2001

Enhanced calcium influx in hippocampal CA3 neurons of spontaneously epileptic rats.

PURPOSE: The spontaneously epileptic rat (SER: tm/tm, zi/zi) shows both absence-like seizures and tonic convulsions. Our previous electrophysiologic studies have demonstrated that SER has abnormal excitability of hippocampal CA3 neurons, which shows a long-lasting depolarization shift by a single stimulation of mossy fibers, probably resulting from the Ca2+ channel abnorrmalities. The present study was performed to determine whether Ca2+ influx is actually enhanced in the CA3 area of SER. METHODS: Hippocampal slices were prepared from normal Wistar rats and SER aged 11-16 weeks old, when the epileptic seizures had been observed, and loaded with fura-2AM. Intracellular Ca2+ concentration ([Ca2+]i) was monitored as the ratio of fluorescence intensities excited at wavelengths of 340 and 380 nm (RF340/F380) with photometric devices. RESULTS: High K+ (10-60 mM) applied to the bath for 2 min increased [Ca2+]i in hippocampal CA1, CA3, and dentate gyrus (DG) areas of both the normal rats and SER in a concentration-dependent manner. However, the high K+-induced increase in [Ca2+]i was significantly more pronounced in the CA3 area of the SER than in that of the normal animals, whereas there were no significant differences in high K+-induced increases of [Ca2+]i in CA1 or DG between the SER and controls. The high K+-induced increases in [Ca2+]i of CA1, CA3, and DG were inhibited by nifedipine (1 to approximately 10 nM), a Ca2+ channel antagonist in both SER and controls. However, the inhibition of the high K+-induced increase in [Ca2+]i by nifedipine (1 nM) was significantly greater in the CA3 area of SER than that of controls. CONCLUSIONS: These findings suggest that Ca2+ influx through the L-type Ca2+ channels is much greater in the CA3 area of SER than in that of normal animals and is involved in the epileptic seizures of the SER.

Animals↗
PubMed2001

Excitation of rat striatal large neurons by dopamine and/or glutamate released from nerve terminals via presynaptic nicotinic receptor (A4beta2 type) stimulation.

Previous in vivo experiments using rats anesthetized with chloral hydrate have revealed that nicotine applied iontophoretically increased firing of striatal neurons receiving excitatory dopaminergic input from the substantia nigra, and nicotine-induced firing was inhibited by domperidone, a dopamine D2 antagonist. The results suggest that nicotine increases release of dopamine from the terminals of dopaminergic neurons. Therefore, we performed the present patch clamp study using slice and acutely dissociated preparations of the rat striatum to elucidate the mechanisms underlying the nicotine-induced excitation of striatal neurons. Application of nicotine (100 microM) to large striatal neurons in slice preparations did not produce any effect on the resting membrane potential, but did increase the frequency of miniature postsynaptic potentials (mpps) and action potentials in all 15 neurons tested. The nicotine-induced increase in mpps and action potentials were inhibited during simultaneous application of domperidone; L-glutamic acid diethyl ester hydrochloride, a non-selective glutamate receptor antagonist; and/or dihydro-beta-erythroidine, a central nicotinic acetylcholine receptor (alpha4beta2 type) antagonist. Postsynaptic current was not induced by nicotine applied by U-tube in 96% of acutely dissociated striatal neurons. The present findings suggest that nicotine mainly acts on the presynaptic nicotinic receptors in the nerve terminals to release neurotransmitters such as dopamine and/or glutamate, thereby activating the striatal large neurons.

Action Potentials↗
PubMed2001

Primary neurotransmitters and regulatory substances onto vestibular nucleus neurons.

This review article focused on the primary neurotransmitters involved in transmission from the otolith to the vestibular nucleus (VN), especially in relation to the neurotransmission to the VN neurons (gravity-sensitive neurons) activated by tilt stimulation. The medial vestibular nucleus (MVN) neurons were classified in 8 types (alpha-theta) according to the patterns in response to the clockwise and counterclockwise tilt-stimulations. The tilt-induced firing was inhibited by GDEE (a non-selective glutamate receptor antagonist) and/or atropine (a muscarinic receptor antagonist). Thus, glutamate and/or acetylcholine may serve as the primary neurotransmitters. This conclusion is supported by the previous findings that glutamate exists in the vestibular nerve and is released from the nerve besides the presence of glutamate receptor subtypes in the VN. In addition, acetylcholine induced atropine-reversible firing of MVN neurons, and the enzymes involved in acetylcholine synthesis/metabolism are also found in the VN. Furthermore, serotonin was found to inhibit the MVN neuronal activities via the 5-HT1A receptors. As such, the 5-HT1A agonist, tandospirone, may be effective in preventing and/or treating motion sickness and/or space sickness.

Acetylcholine↗
PubMed2001

[Function of monoamine neurotransmitter transporters].

Monoamine transporters include plasma membrane and vesicular monoamine transporters(VMAT). The former selectively and Na+/Cl(-)-dependently transport dopamine, noradrenaline and serotonin into the cytoplasma, and the latter non-selectively carries monoamine into the vesicle. These transporters are composed of amino acid groups containing 12 folds more transmembrane components. Cytoplasmic transporters are a target site of certain drugs. Antiepileptic drugs such as SSRI and tricyclic antidepressants bind with serotonin transporter(SERT), noradrenaline transporter(NET) and/or dopamine transporters(DAT) to inhibit transport of monoamines into the cytoplasma, thereby increasing monoamine levels within the synaptic cleft. However, amphetamine, known to induce drug dependence, is transported by DAT and inhibit VMAT to induce reverse-transport of monoamines into the synaptic area, thereby producing psychiatric and behavioral alterations. Thus, monoamine transporters are target sites of drugs, and functional changes in the transporters may be involved in the pathogenesis of affective diseases, schizophrenia and/or personality disorders including neurogenerative diseases such as Parkinson's disease.

Animals↗
PubMed2000

Detection of chromosomal aneusomy by fluorescence in situ hybridization in fine-needle aspirates from breast tumors: application to the preoperative diagnosis of breast carcinoma.

BACKGROUND: The authors studied the clinical usefulness of fluorescence in situ hybridization (FISH) analysis of a numerical aberration of chromosomes (aneusomy) using fine-needle aspiration (FNA) samples from patients with breast tumors in the preoperative diagnosis of breast carcinoma. METHODS: FNA samples were obtained from 176 breast tumors and were subjected to conventional cytology and FISH analysis using the centromere probes for chromosomes 1, 11, and 17. Patients with FNA samples that showed aneusomy in at least one of the three chromosomes were diagnosed as positive. RESULTS: Histologic examination revealed 157 malignancies and 19 benign results (10 fibroadenomas, 6 intraductal papillomas, 1 intracystic papilloma, and 2 ADH). The sensitivity, specificity, and diagnostic accuracy were 85.4%, 94.7%, and 86.4%, respectively, for cytology and 90.4%, 100%, and 91.5%, respectively, for FISH. Of 15 breast malignancies that were diagnosed with indeterminate cytology, 13 were diagnosed as positive with FISH analysis (sensitivity, 86.7%). CONCLUSIONS: The results demonstrate that the use of FISH in the diagnosis of FNA samples has a diagnostic accuracy comparable to conventional cytology and is useful in making a definitive diagnosis of malignancy (100% specificity) in patients with indeterminate cytologic results, suggesting that FISH diagnosis can be a good adjunct to conventional cytology.

Adult↗
PubMed2000

Activation by nicotine of striatal neurons receiving excitatory input from the substantia nigra via dopamine release.

An electrophysiological study was performed to elucidate the role of nicotinic receptors in the striatal neurons in chloral hydrate-anesthetized rats. The effects of microiontophoretic application of nicotine and other drugs were examined on the caudate nucleus (CN) neurons activated monosynaptically by stimulation of the substantia nigra pars compacta (SN). Application of nicotine facilitated spontaneous firing. The nicotine-induced firing of the CN neurons was inhibited by concomitant application of domperidone or hexamethonium. These findings suggested that nicotine enhances dopamine release from the SN-derived dopaminergic nerve terminals by activating the neurons via D2 receptors.

Action Potentials↗
PubMed2000

Effects of sigma(1) receptor agonist SA4503 and neuroactive steroids on performance in a radial arm maze task in rats.

This study examined the effects of sigma(1) receptor agonist SA4503 and neuroactive steroids dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate (PREGS) and progesterone (PROG) on spatial working and reference memory in a radial arm maze task in rats. The insertion of a 6-min delay between the 2nd and 3rd choices caused a specific decline in working memory, but had no effect on reference memory. This decline in working memory was improved by SA4503, but not by DHEAS, PREGS or PROG. A non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine significantly impaired both working and reference memory in the presence or absence of a delay. The dizocilpine-induced impairments in the presence of a 6-min delay were ameliorated by SA4503, DHEAS and PREGS, whereas PROG had no effect. The beneficial effects of SA4503, DHEAS and PREGS were antagonized by treatment with sigma(1) receptor antagonist N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-ethylamine hydrochloride (NE-100). Furthermore, PROG attenuated the ameliorating effects of SA4503, DHEAS and PREGS on dizocilpine-induced memory deficits. These results suggest that sigma(1) receptors play a significant role in short-term working memory. Furthermore, it is suggested that DHEAS and PREGS ameliorate dizocilpine-induced memory impairments by acting as sigma(1) receptor agonists, while PROG antagonizes their effects by acting as a sigma(1) receptor antagonist.

Animals↗
PubMed2000

Altered hippocampal expression of neuropeptide Y, somatostatin, and glutamate decarboxylase in Ihara's epileptic rats and spontaneously epileptic rats.

By in situ hybridization and immunocytochemistry, expression of neuropeptide Y (NPY), somatostatin and glutamate decarboxylase 65 (GAD65) was studied in the hippocampus of two different epileptic mutant rats, Ihara's epileptic rat (IER) and the spontaneously epileptic rat (SER). GAD65 mRNA expression was enhanced in interneurons of the hippocampus in young IER, that had not yet developed generalized seizures. In older IER and older SER that both showed spontaneous seizures, marked increases of NPY mRNA in hippocampal granule cells and interneurons were found, as well as elevated GAD65 mRNA levels in interneurons. NPY immunoreactivity was enhanced in hilar interneurons and the dentate gyrus of older IER. In addition, some older IER stained heavily for NPY in mossy fibers. These findings suggest that up-regulation of NPY and GAD65 synthesis may be important in epileptogenesis.

Animals↗
PubMed2000

Epileptic seizures induced by N-acetyl-L-aspartate in rats: in vivo and in vitro studies.

Tremor rat (tm/tm), the parent strain of spontaneously epileptic rat (SER: zi/zi, tm/tm), exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes on cortical and hippocampal electroencephalograms (EEG) after 10 weeks of age, prior to development of convulsive seizures. Recently, this animal model has been demonstrated to display a genomic microdeletion within the critical region of tm, where aspartoacylase hydrolyzing N-acetyl-L aspartate (NAA) is located, besides showing the ability to accumulate NAA in the brain. Therefore, the present study was performed to determine the involvement of NAA in the induction of epileptic seizures. When NAA (4 micromol) was applied intracerebroventricularly (i.c.v.) to normal Wistar rats, 4-10 Hz polyspikes and/or spike-wave-like complexes followed by absence-like seizure before persistent 1-5 Hz waxing high-voltage after-discharges were observed on cortical and hippocampal EEG. At a higher dose (8 micromol), NAA induced convulsive seizures. The absence-like seizures with polyspikes and/or spike-wave-like complexes on the EEG were also observed with i.c.v. NAA in premature tremor rats without seizures. The NAA-induced seizures in normal rats were antagonized by i.c.v. glutamic acid diethyl ester, a non-selective glutamate receptor antagonist. In addition, NAA applied to the bath rapidly induced a long-lasting depolarization concomitantly with repetitive firings in hippocampal CA3 neurons of normal rat brain slice preparations. These findings suggest that NAA is involved in the induction of absence-like seizures and/or convulsion, probably via glutamate receptors.

Animals↗
PubMed2000

alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.

It is now clear that alpha(1)-adrenoceptors comprise a heterogeneous family. In the present study, we characterized the alpha(1)-adrenoceptor subtype in the nasal mucosa vasculature of guinea pigs. A rectangular strip of guinea pig nasal mucosa was suspended in an organ bath containing Krebs' bicarbonate solution. Changes in tension were recorded isometrically. Concentration-response curves for agonists were obtained in a cumulative manner. Noradrenaline produced the greatest contraction of the nasal mucosa vasculature. NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride) and oxymetazoline worked as partial agonists. The intrinsic activities of NS-49 and oxymetazoline were 0.50+/-0.22 and 0.29+/-0.17, respectively, compared with noradrenaline (=1.00). Prazosin and the putative alpha(1A)-adrenoceptor antagonists WB-4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane) and 5-methylurapidil antagonized the response to noradrenaline competitively (pA(2) for prazosin<9.0). Conversely, putative alpha(1B) and alpha(1D)-adrenoceptor antagonists (spiperone and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione), respectively) did not antagonize competitively. These results suggest that the alpha(1A)-subtype is predominant and that the alpha(1L) (or alpha(1N)) subtype may also be present in the guinea pig nasal mucosa vasculature. Furthermore, NS-49 might prove to be a nasal mucosa vasoconstrictor, which will improve nasal obstruction.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2000

Human papillomavirus type 33 DNA in breast cancer in Chinese.

BACKGROUND: The association between human papillomavirus (HPV) and anogenital tumors, especially cervical cancer, is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer. METHODS: We used PCR and Southern blot hybridization to analyze HPV-related DNA specimens from 32 cases of invasive ductal carcinoma operated upon in the Shanghai region of China. RESULTS: DNA derived from HPV33 was detected in 14 cases (43.8%). No HPV16 or HPV18 DNA was detected in any of the cases in this study. This is the first report demonstrating a correlation between HPV33 infection and breast cancer. CONCLUSIONS: Our results suggest that HPV33 infection may be involved in the pathogenesis of breast cancer in Chinese.

Adult↗