Formamide denaturation of chromosomal DNA for in situ hybridization and c-band preparation in the guinea pig, Cavia porcellus

1. Protein disulphide-isomerase and glutathione-insulin transhydrogenase activities were assayed in parallel through a conventional purification of protein disulphide-isomerase from ox liver. 2. Throughout a series of purification steps (differential centrifugation, acetone extraction, (NH4)2SO4 precipitation and ion-exchange chromatography), the two activities appeared in the same fractions but were purified to different extents. 3. The final sample was 143-fold purified in protein disulphide-isomerase but only 10-fold purified in glutathione-insulin transhydrogenase; nevertheless the two activities in this preparation were not resolved by high-resolution isoelectric focusing and both showed pI4.65. 4. In a partially purified preparation containing both activities, glutathione-insulin transhydrogenase was far more sensitive to heat denaturation than was protein disulphide-isomerase; conversely protein disulphide-isomerase was more sensitive to inactivation by deoxycholate. 5. The data are inconsistent with a single enzyme being responsible for all the protein disulphide-isomerase and glutathione-insulin transhydrogenase activity of ox liver. It is suggested that several similiar thiol-protein disulphide oxidoreductases of overlapping specificities may better account for the data.     

Effects of olfactory bulbectomy on social behavior of male guinea pigs ( Cavia porcellus ).

Studied the effects of olfactory bulbectomy on social behavior in 16 male guinea pigs. Both brief exposure pairing techniques and a group-living observation period were employed to test for disruption. During short-term testing sessions bulbectomized Ss courted females less than but mounted them as frequently as controls. While the groups did not differ in fighting behavior during short-term tests, controls scent-marked more frequently. Subsequently, Ss were observed as same-treatment pairs living continuously with females, and behavior was sampled over a 3-wk period. Under these conditions bulbectomized males, unlike controls, failed to form dominance orders, exhibited virtually no intermale aggressive activity, had markedly depressed sexual activity, and scent-marked rarely. It is concluded that olfactory bulbectomy profoundly alters the behavior of male domestic guinea pigs and that those alterations are most evident when experimental Ss are observed in a species-typical group-living environment. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat

The modulatory effects of electrical and chemical (glutamate) stimulation in the rostral ventromedial medulla (RVM) on spinal nociceptive transmission and a spinal nociceptive reflex were studied in rats. Electrical stimulation at a total 86 sites in the RVM in the medial raphe nuclei (n = 54) and adjacent gigantocellular areas (n = 32) produced biphasic (facilitatory and inhibitory, n = 43) or only inhibitory (n = 43) modulation of the tail-flick (TF) reflex. At these 43 biphasic sites in the RVM, facilitation of the TF reflex was produced at low intensities of stimulation (5-25 microA) and inhibition was produced at greater intensities of stimulation (50-200 microA). At 43 sites in the RVM, electrical stimulation only produced intensity-dependent inhibition of the TF reflex. Activation of cell bodies in the RVM by glutamate microinjection reproduced the biphasic modulatory effects of electrical stimulation. At biphasic sites previously characterized by electrical stimulation, glutamate at a low concentration (5 nmol) produced facilitation of the TF reflex; a greater concentration (50 nmol) only inhibited the TF reflex. In electrophysiological experiments, electrical stimulation at 62 sites in the RVM produced biphasic (n = 26), only inhibitory (n = 26), or only facilitatory (n = 10) modulation of responses of lumbar spinal dorsal horn neurons to noxious cutaneous thermal (50 degrees C) or mechanical (75.9 g) stimulation. Facilitatory effects were produced at lesser intensities of stimulation and inhibitory effects were produced at greater intensities of stimulation. The apparent latencies to stimulation-produced facilitation and inhibition, determined with the use of a cumulative sum method and bin-by-bin analysis of spinal neuron responses to noxious thermal stimulation of the skin, were 231 and 90 ms, respectively. The spinal pathways conveying descending facilitatory and inhibitory influences were found to be different. Descending facilitatory influences on the TF reflex were conveyed in ventral/ventrolateral funiculi, whereas inhibitory influences were conveyed in dorsolateral funiculi. The results indicate that descending inhibitory and facilitatory influences can be simultaneously engaged throughout the RVM, including nucleus raphe magnus, and that such influences are conveyed in different spinal funiculi.     

Effects of cortical stimulation on red nucleus neurons in the guinea pig

The aim of the present work was to study the control that the cerebral cortex exerts on red nucleus (RN) neurons in the guinea pig. The experiments were carried out in anaesthetized animals. Electrical stimulation of localized cortical foci was performed by tungsten microelectrodes in frontal and parietal regions containing sensorimotor representations of the body. Single unit RN activity was extracellularly recorded through glass micropipettes, and the encountered RN neurons were recognized by searching their peripheral receptive field. Then, corticorubral influences were tested on RN neurons whose receptive field was located in the same body regions where motor responses were evoked by cortical stimulation. The stimulation with a single pulse evoked complex responses, typically consisting of long lasting inhibitions sometimes preceded by a weak facilitation and always followed by an excitatory rebound. The application of a second pulse modified this pattern, depending on the time interval between the two stimuli. In fact, the reduction of the interval below 300 ms enhanced the excitatory components whereas it shortened the inhibitory component; moreover, an "early" facilitation was evoked but only at intervals as short as 50-150 ms, or less. These results suggest that the corticorubral control may vary according to different levels of cortical activation, becoming more and more facilitatory as the cortical discharges increase from low frequency values (tonic activity) towards high frequency values (phasic activity).     

Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.     

Motivated behaviors elicited from hypothalamus, midbrain, and pons of the guinea pig (Cavia porcellus).

Eating, drinking, biting attack, male mating behavior, and gnawing were elicited by electrical stimulation through electrodes located predominantly in a region extending from the preoptic area through the lateral hypothalamus into the ventral midbrain. Escape and digging were elicited from a parallel but more medial region that overlapped the lateral zone only in the preoptic-anterior hypothalamic area. Several differentiable vocalizations were produced from sites distributed through most, although not all, areas explored. Sites yielding painlike responses were located principally in the vicinity of the presumed pain pathway traced after anterolateral cordotomy in other species. Reward was obtained from widespread sites that were generally congruent with catecholaminergic systems as described in the rat. Although there was considerable overlap of the effective zones for many responses, their underlying mechanisms were differentiated anatomically by localized differences in their distribution or functionally by the elicitation of pure responses from some electrodes. Response mechanisms localized in the brain stem of the guinea pig generally resembled those in the rat, although there were differences in details, especially in the posterior midbrain and pons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

5-HT autoreceptors in the regulation of 5-HT release from guinea pig raphe nucleus and hypothalamus

5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig dorsal raphe nucleus have been studied in comparison with those in the hypothalamus. In vitro release was measured in slices of raphe and hypothalamus prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5-CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT evoked by electrical stimulation in either of these regions when given alone. The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions. Methiothepin and GR127935 (100-1000 nM) shifted to the right the concentration-effect curve of 5-CT in both the raphe and the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration-effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the hypothalamus. In microdialysis experiments ketanserin, applied locally at 10 microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of the freely moving guinea pig, whereas 5-HT levels were unchanged in the hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10 microM in raphe and 0.1 microM in hypothalamus), in the raphe or the hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM, did not prevent naratriptan (10 microM) from reducing the extracellular levels of 5-HT. These results suggest that, in the conditions used in this study, the release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5-HT1B receptors but essentially the control is through 5-HT receptors whose subtype is still to be determined. In the hypothalamus, however, it is clear that only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.     

Release of cerebral 5-hydroxytryptamine evoked by electrical stimulation of the dorsal and median raphe nuclei: effect of a neurotoxic amphetamine

Recent neuroanatomical data suggest that the axons and terminals of serotonergic neurons of the dorsal and median raphe nuclei are morphologically and pharmacologically distinct. Here we attempted to establish a functional in vivo model of serotonergic terminals derived from these nuclei, and then carry out a preliminary comparison of their physiological and pharmacological properties. Brain microdialysis was used to monitor extracellular 5-hydroxytryptamine in the hippocampus (dorsal and median raphe innervation) and frontal cortex (preferential dorsal raphe innervation) of the anaesthetized rat. To distinguish 5-hydroxytryptamine released by terminals of dorsal raphe neurons from that released by median raphe neurons, one or other of these nuclei was stimulated electrically. Electrical stimulation of either the dorsal or median raphe nucleus evoked a release of 5-hydroxytryptamine in the hippocampus. Whereas stimulation of the dorsal raphe nucleus also released 5-hydroxytryptamine in the frontal cortex, stimulation of the median raphe nucleus did not. No release of 5-hydroxytryptamine was evoked when electrodes were located in regions bordering the dorsal raphe nucleus and the median raphe nucleus. The amounts of hippocampal 5-HT released by stimulation of the dorsal or median raphe nucleus were found to be similarly altered by a 5-hydroxytryptamine uptake inhibitor (citalopram) and calcium-free perfusion medium, and also by increasing stimulation frequency (2-10 Hz). Furthermore, the amount of 5-hydroxytryptamine released by electrical stimulation of either the dorsal raphe nucleus or median raphe nucleus was markedly reduced in rats pretreated with p-chloroamphetamine. In summary, our data show that electrical stimulation of the dorsal or median raphe nucleus releases 5-hydroxytryptamine in a regionally specific manner (hippocampus versus frontal cortex), suggesting that serotonergic nerve terminals of the dorsal and median raphe pathways were being activated selectively. Using this model, we found no differences in the responsiveness of dorsal and median raphe pathways to a specific set of physiological and pharmacological manipulations. In particular, our data suggest that the neurotoxic action of p-chloroamphetamine may not be targeted solely on serotonergic axons and terminals of the dorsal raphe nucleus but includes those of the median raphe nucleus.     

Respiratory and cardiovascular effects of prostaglandins in the conscious guinea pig

A technique to assess respiratory and cardiovascular effects of prostaglandins (PGs) in conscious guinea pigs was developed. Animals were placed in a plethysmograph and tidal volume, airflow, and heart rate were recorded. In addition, blood pressure and/or pleural pressure were obtained. Some experiments involved the use of a pulmonary calculator that processed the appropriate pulmonary signal and provided on-line readout of dynamic compliance and airway resistance. Aerosolized antagonists were evaluated for their ability to block responses to aerosolized histamine. We found the relative antagonistic potencies of PGE1, PGE2, isoproterenol, and salbutamol to be 5.5, 2.3, 1 and 0.2, respectively. Aerosolized PGE1 and PGE2 but not PGF2alpha given prior to histamine caused decreases in tidal volume, airflow and heart rate. These effects were not seen in animals that were prepared for measurements involving invasive surgical techniques. The aerosolized PGE2 induced tidal volume changes were not prevented by pretreatment with salbutamol, chlorpheniramine, atropine or hexamethonium, though the latter two drugs inhibited the fall in heart rate. We suggest that the bradycardia following aerosolized PGE2 administration may originate from airway irritant receptors. The results validate use of our methods for the assessment of responses to bronchoactive agents under physiological conditions.     

Antitumor effects elicited by antisense-mediated downregulation of the insulin-like growth factor I receptor (review)

The parasporal inclusion proteins of the type strain of Bacillus thuringiensis serovar higo (H44), that have moderate mosquitocidal activity, were characterized. The purified parasporal inclusions, spherical in shape, were examined for activity against the two mosquito species, Culex pipiens molestus and Anopheles stephensi and the moth-fly, Telmatoscopus albipunctatus. The LC50 values of the inclusion for the two mosquitoes were 3.41 and 0.15 microgram.ml-1, respectively. No mortality was shown for T. albipunctatus larvae by the inclusions at concentrations up to 1 mg ml-1. Solubilized parasporal inclusions exhibited no haemolytic activity against sheep erythrocytes. Parasporal inclusions consisted of eight proteins with molecular masses of 98, 91, 71, 63, 59, 50, 44 and 27 kDa. Of these, the 50 and 44 kDa proteins were the major components. Analysis with immunoblotting revealed that, among several inclusion proteins of B. thuringiensis serovar israelensis, only two proteins of 130 kDa and 110 kDa reacted weakly with antibodies against higo proteins. N-terminal amino acid sequences of the 98, 91, and 71 kDa proteins showed 85-100% identity to those of the two established Cry protein classes, Cry4A and Cry10A.     

Role of the nucleus raphe obscurus in the inhibition of rostral ventrolateral medullary neurones induced by stimulation in the ventrolateral periaqueductal grey matter of the rabbit

The uptake, partitioning, and release of ingredients such as water, oil, surfactant, and ions are important factors to understand and control in the design and manufacture of detergent and personal products. Although conventional pulse NMR (PNMR) spectroscopy continues to be used to analyse bulk molecular mobility and phase composition, more recently MR imaging techniques have created unique opportunities for gaining spatial information about these processes in ways that are noninvasive and potentially quantitative. This paper describes the evaluation of MRI and associated PNMR techniques to study transport in three relevant cases: ion diffusion (e.g., fluoride) in concentrated dispersions, oil transport through powders, and water ingress into porous powders (zeolite). Results are presented to illustrate the potential of multiple pulse and gradient echo MRI methods for dealing with the short T2 scenarios that represent a common problem in quantitative imaging of water in solid-containing composites involving, for instance, zeolite, or silica. Pore-size characterisation results are also presented.     

Beta-frequency (15-35 Hz) electroencephalogram activities elicited by toluene and electrical stimulation in the behaving rat

Bursts of beta-frequency (15-35 Hz) electroencephalogram activity occur in the olfactory system during odour sampling, but their mode of propagation within the olfactory system and potential contribution to the mechanisms of learning and memory are unclear. We have elicited large-amplitude beta activity in the rat olfactory system by applying noxious olfactory stimuli (toluene), and have monitored the bursts via chronically-implanted electrodes. Following exposure to toluene, coherent bursts with a peak frequency of 19.8 +/- 0.9 Hz were observed in the olfactory bulb, piriform cortex, entorhinal cortex and dentate gyrus. The timing of the bursts and the phases of electroencephalogram cross-spectra indicate that beta bursts propagate in a caudal direction from the olfactory bulb to the entorhinal cortex. The time delays between peaks of bursts in these structures were similar to latency differences for field potentials evoked by olfactory bulb or piriform cortex test-pulses. Peaks of burst cycles in the dentate region, however, were observed just prior to those in the entorhinal cortex. Surprisingly, power in toluene-induced beta-frequency oscillations was not increased following long-term potentiation induced by tetanic stimulation of the olfactory bulb, piriform cortex and entorhinal cortex. The activity of local inhibitory mechanisms may therefore counteract the effects of synaptic enhancements in afferent pathways during beta bursts. Low-frequency electrical stimulation of the piriform cortex was most effective in inducing coherent oscillatory responses in the entorhinal cortex and dentate gyrus at stimulation frequencies between 12 and 16 Hz. The results show that repetitive polysynaptic volleys at frequencies in the beta band induced by either toluene or electrical stimulation are transmitted readily within the olfactory system. The propagation of neural activity within this frequency range may therefore contribute to the transmission of olfactory signals to the hippocampal formation, particularly for those odours which induce high-amplitude bursts of beta activity.     

Effects of stimulation parameters on behavior elicited by stimulation of the hypothalamic defense area.

Elicited agonistic behavior by stimulating the ventromedial hypothalamus of 22 domestic cats. 12 different behavioral components were rated separately. Behavioral alerting, mydriasis, retraction of ears, piloerection, hissing, and protrusion of claws were the most characteristic components. The parameters of the stimulus were shown to be important determinants of the nature of the behavior. Results suggest that either discrete central neural circuits for the different components of agonistic behavior are diffusively organized within the ventromedial hypothalamus, or the components result from a general activation of neurons subserving discrete fixed-action patterns, the resultant behavior being determined by different factors, such as the intensity of the activation. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of electrical stimulation of the superior cervical ganglion on cochlear blood flow in guinea pig

A twenty-four-hour blood pressure (BP) monitoring was performed in 20 normotensive and 20 hypertensive subjects, matched by sex and age. Blood pressure and heart rate (HR) variability were evaluated both as absolute and percent standard deviation. In agreement with the literature no significant difference in HR and BP variability was observed between the two groups. The linear regression between HR and BP values was evaluated in both groups. The authors observed a significant difference in the relationship between these two cardiovascular variables between the two groups. In the hypertensive group the cardiovascular control of HR and BP showed a different relationship than in normotensive subjects, suggesting a different neurovegetative modulation.     

The delayed effects of ethacrynic acid on the stria vascularis of the guinea pig

Guinea pigs were administered 40 mg ethacrynic acid per kg b.wt. and sacrificed at 30-48 minutes, 3-4 hours, 2 or 7 days post-drug. Cochlear potentials (EP and CP) were monitored before sacrifice. At 30-48 minutes, the potentials had decreased considerably, and a marked edema plus cytological changes were visible in the stria vascularis. The potentials had recovered to about 75% of their original value at 3-4 hours; some cell recovery was visible, but the edema was still present. Potentials recorded from the basal turn were normal at 2 and 7 days, although some strial cells showed deterioration.     

The effects of ginkgolide B (BN52021) on guinea pig vestibular nucleus neurons in vitro: importance of controlling for effects of dimethylsulphoxide (DMSO) vehicles

Electricity properties of polybutylcyanoacrylate nanoparticles (PBCA-NP) were studied by using a U-tube electrophoresis apparatus. It was proved that all the PBCA-NP is negatively charged. The surface potential of PBCA-NP is directly proportional to the concentration of stabilizer (Dextran 70) and the pH value of the medium, while it is inversely proportional to the concentration of butylcyanoacrylate and the model drug (gentamycin). The effect of ion strength on surface potential is obvious but not linear. The effect of stabilizers and surfactants used on the surface potential is evident while the effect of electrolytes is indistinct under the experimental conditions.     

Induction of long-term receptive field plasticity in the auditory cortex of the waking guinea pig by stimulation of the nucleus basalis.

Learning induces neuronal receptive field (RF) plasticity in primary auditory cortex. This plasticity constitutes physiological memory as it is associative, highly specific, discriminative, develops rapidly, and is retained indefinitely. This study examined whether pairing a tone with activation of the nucleus basalis (NB) could induce RF plasticity in the waking guinea pig and, if so, whether it could be retained for 24 hrs. Subjects received 40 trials of a single frequency paired with electrical stimulation of the NB at tone offset. The physiological effectiveness of NB stimulation was assessed later while subjects were anesthetized with urethane by noting whether stimulation produced cortical desynchronization. Subjects in which NB stimulation was effective did develop RF plasticity and this was retained for 24 hrs. Thus, activation of the NB during normal learning may be sufficient to induce enduring physiological memory in auditory cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig

We evaluated the airway activity of the novel phosphodiesterase type 4 inhibitor SB 207499 [Ariflo; c-4-cyano-4-(3-cyclopentyloxy-4-methoxyp henyl-r-1-cyclohexane carboxylic acid)], in the guinea pig. Ovalbumin (OA)-induced contractions of guinea pig isolated tracheal strips were inhibited by SB 207499 with an EC50 of 1 microM but had little or no effect on exogenous agonist-induced contraction, which suggests that its effect on OA-induced contraction in vitro is primarily due to inhibition of mediator release from mast cells. In anesthetized guinea pigs, SB 207499 inhibited OA-induced bronchoconstriction with i.v. and p.o. ID50 values of 1.7 and 17 mg/kg, respectively. At 1, 3 and 6 hr after SB 207499 (30 mg/kg p.o.), OA-induced bronchospasm was inhibited by 92%, 70% and 58%, respectively, corresponding to elevated plasma concentrations of 1.62 +/- 0.19, 1.65 +/- 0.29 and 0. 93 +/- 0.24 microg/ml, respectively, of SB 207499. SB 207499 also inhibited house dust mite-induced bronchoconstriction (ID50 = 0.9 mg/kg i.v. and 8.9 mg/kg p.o.). In contrast to its lack of bronchorelaxant activity in vitro, SB 207499 inhibited bronchospasm induced by i.v. leukotriene D4 (LTD4) [ID50 = 3 mg/kg i.v.]. The bronchorelaxant effect of i.v.-administered SB 207499 was at least additive with that of salbutamol in reversing infused histamine-enhanced airway tone, but it did not alter base line or enhance salbutamol-induced cardiovascular effects. In conscious guinea pigs, SB 207499 (10 or 30 mg/kg p.o.), 1 hr before antigen or LTD4 challenge, markedly reduced bronchospasm and subsequent eosinophil influx as measured by bronchoalveolar lavage 24 hr after provocation. SB 207499 administered after OA or LTD4 challenge also reduced airway eosinophilia measured at 24 hr after OA challenge or 96 hr after LTD4 challenge. These results, coupled with the broad anti-inflammatory activity of SB 207499 previously described (Barnett et al., 1998), suggest that SB 207499 will be useful in the treatment of asthma and other inflammatory disorders.     

Median raphe (parameatal) cysts of the penis

PURPOSE: Although median raphe cysts of the penis have been widely reported the pathogenesis is obscure. We describe the microstructural detection of 3 cases of median raphe to study the true pathogenesis. MATERIALS AND METHODS: Three patients presented to our clinic of plastic surgery complaining of abnormal shape of the penis or mass recurrence. High magnification light microscopy and electron microscopy were performed. RESULTS: Microstructural study revealed that all 3 cases had similar findings to those of the common urethral mucosa. CONCLUSIONS: Median raphe cysts are derived from the external paraurethral ducts and contain features that to our knowledge have not been previously reported.     

The effects of flunarizine and pentoxifylline on vestibular blood flow in the guinea pig

Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear. Changes in VBF were evaluated from the posterior semicircular canal ampulla in guinea pigs using a laser Doppler flowmeter. One group of animals was infused with pentoxifylline at concentrations of 10-40 mg/ml, while a second group was treated with 0.3-1.5 mg/kg flunarizine. VBF, blood pressure (BP) and heart rate (HR) were monitored continuously. Findings showed that pentoxifylline induced a concentration-dependent increase in VBF. In contrast, no increase in VBF occurred in response to flunarizine infusions. These studies suggest that the effectiveness of pentoxifylline in the clinical treatment of vestibular disorders may be the result of improved blood flow.