Administration In Guinea Pigs Research Articles

Ocular Posterior Segment Distribution and Pharmacokinetics of Brimonidine After Intravitreal Administration in Guinea Pigs.

Purpose: Brimonidine is a highly alpha-2 adrenergic agonist, which provides a potential myopia control effect. This study aimed to examine the pharmacokinetics and concentration of brimonidine in the posterior segment tissue of eyes in guinea pigs. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was successfully used for brimonidine pharmacokinetics and tissue distribution research in guinea pigs following intravitreal administration (20 μg/eye). Results: Brimonidine concentrations in the retina and sclera were maintained at a high level (>60 ng/g) at 96 h postdosing. Brimonidine concentration peaked in the retina (377.86 ng/g) at 2.41 h and sclera (306.18 ng/g) at 6.98 h. The area under curve (AUC0-∞) was 27,179.99 ng h/g in the retina and 39,529.03 ng h/g in the sclera. The elimination half-life (T1/2e) was 62.43 h in the retina and 67.94 h in the sclera. Conclusions: The results indicated that brimonidine was rapidly absorbed and diffused to the retina and sclera. Meanwhile, it maintained higher posterior tissue concentrations, which can effectively activate the alpha-2 adrenergic receptor. This may provide pharmacokinetic evidence for the inhibition of myopia progression by brimonidine in animal experiments.

Low doses and short duration of prednisolone administration in guinea pigs experimentally infected with Schistosoma haematobium: Histopathology of liver and lungs

In our previous study, administration of 5 mg prednisolone for five days pre-Schistosoma haematobium infection in guinea pigs increased susceptibility and produced pathological reactions in the liver and bladder. Since corticosteroids can suppress granuloma formation, maturation, and size, this study sought to investigate if prednisolone given at low doses and short duration can produce granulomatous lesions in the tissues of guinea pigs experimentally infected with S. haematobium. Guinea pigs were shared into six groups: group I and II were the immunosuppressed-infected guinea pigs (I0.5 and I1.5- 20 animals each), group III was the unimmunosuppressed-infected guinea pigs (UI- 20 animals), and group IV, V and VI were the immunosuppressed-uninfected and normal guinea pigs (D0.5, D1.5, and normal- 10 animals each). Prednisolone was given in doses of 0.5 mg/kg and 1.5 mg/kg to the different groups, a day before infection and on day 5 post-infection. The infected groups were subcutaneously injected with 250–300 S. haematobium cercariae. Screening for S. haematobium eggs in urine and fecal samples of animals, and quantitative analysis for leukocyte and red blood cell (RBC) counts in urine samples of guinea pigs began nine weeks post-infection (WPI). Guinea pigs were killed, perfused, worms recovered and sections of the liver, lungs, and bladder excised for histopathological examination at 6, 8, 11, 14 and 16 WPI. S. haematobium eggs were only seen in urine samples of I1.5 at 15 and 16WPI. Although the parasite eggs were seen in fecal samples of all infected guinea pigs from 9WPI, those of UI were sparse and took longer time to hatch. High leukocyte counts were seen in all immunosuppressed groups at 6WPI, which returned to normal levels in D1.5 and D0.5 at 16WPI. At 16WPI, significant numbers of leukocyte and RBC counts were seen in urine samples of I1.5. The immunosuppressed-infected groups had significant numbers of mature and total worm loads than UI group (p > 0.05). However, the worm burden of I1.5 was higher than I0.5 at 14WPI and 16WPI. Non-granulomatous lesions were only recorded in the liver sections of the immunosuppressed-infected animals and in lung sections of UI and I1.5 guinea pigs. Liver lesions seen were hepatocyte degeneration; necrosis; Kupffer cell involvements as hyperplasia, phagocytosis, proliferation; hyperaemia and haemorrhage, and mononuclear leukocyte infiltration. Lung lesions seen in I1.5 at 11-16WPI were hemosiderin depositions and hyperaemia, emphysema and atelectasis, and mononuclear leukocyte infiltrations while in UI, emphysema and mononuclear leukocyte infiltration were seen only at 16WPI. In the immunosuppressed-infected groups, composite liver lesion scores showed that peak lesion severity was at 8WPI and 11WPI in I1.5 and I0.5, respectively. However, there was no significant difference (p = 0.105) in composite liver lesion scores of I1.5 and I0.5. Lung lesion score of UI at 16WPI was significantly higher (p > 0.05) than that of I1.5. Findings from this study show that even at low doses and short duration of administration, corticosteroids can only increase susceptibility of guinea pigs but cannot improve its suitability as experimental models of S. haematobium infection.

Cardiovascular and hemodynamic consequences of recombinant placental growth factor administration in Guinea pigs

ABSTRACT Placental growth factor (PlGF), a member of the vascular endothelial growth factor family of proteins regulating angiogenesis, has been shown to have acute vasodilatory effects on human resistance arteries. However, the acute hemodynamic effects of PlGF in vivo are not known. The aim of this study was to report acute cardiovascular changes induced by recombinant human PlGF administered intravenously in male Guinea Pigs with implanted telemeters. PlGF decreased mean arterial blood pressure by 10–20% within minutes. The magnitude of reduction was similar at three dose levels; however, the duration of relative hypotension was dose-dependent. Blood pressure reduction resulted in a compensatory increase in heart rate, or reflex tachycardia. To rule out any direct effect on the heart, PlGF was tested in the ex vivo Langendorff heart preparation, and no cardiac changes were found. Together these results suggest that the PlGF-related changes in blood pressure are largely mediated by its actions in the vasculature.

O-001. Acute cardiovascular and hemodynamic consequences of placental growth factor administration in guinea pigs

O-001. Acute cardiovascular and hemodynamic consequences of placental growth factor administration in guinea pigs

Silk-coated dexamethasone non-spherical microcrystals for local drug delivery to inner ear

The local drug delivery systems play an important role in treating sudden sensorineural hearing loss. In this work, we synthesized dexamethasone microcrystals (DEX MCs) using precipitation technique followed by silk coating via layer-by-layer assembly. Compared to raw DEX, the physicochemical properties including shape, crystal form, dispersity, dissolution or sustained release, of DEX MCs or poly-l-lysine/silk fibroin (PLL/SF) multilayers-coated DEX MCs (DEX-(PLL/SF)3) were investigated. More importantly, after a single intratympanic administration in guinea pigs, DEX-(PLL/SF)3 was uniformly distributed on the round window membrane (RWM) in comparison with raw DEX and DEX MCs. And increased concentration of DEX treatment resulted in higher perilymph DEX levels. No significant morphological change and inflammatory responses on the cochlear tissue were observed. Thus, the DEX-(PLL/SF)3 formulation could be a novel local drug delivery strategy to realize safe, efficient and sustainable DEX delivery into inner ear across RWM.

Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration in guinea pigs (Cavia porcellus).

To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in guinea pigs (Cavia porcellus). 8 healthy adult guinea pigs (4 sexually intact females and 4 sexually intact males). In a crossover study, hydromorphone (0.3 mg/kg) was administered once IM (epaxial musculature) or IV (cephalic catheter) to each guinea pig at a 1-week interval (2 treatments/guinea pig). Blood samples were collected before and at predetermined intervals after drug administration via a vascular access port. Plasma hydromorphone concentrations were determined by liquid chromatography-tandem mass spectrometry. Noncompartmental analysis of data was used to calculate pharmacokinetic parameters. Mean ± SD clearance and volume of distribution for hydromorphone administered IV were 52.8 ± 13.5 mL/min/kg and 2.39 ± 0.479 L/kg, respectively. Mean residence time determined for the IV and IM administration routes was 0.77 ± 0.14 hours and 0.99 ± 0.34 hours, respectively. The maximum observed plasma concentration following IM administration of hydromorphone was 171.9 ± 29.4 ng/mL. No sedative effects were observed after drug administration by either route. Pharmacokinetic data indicated that hydromorphone at a dose of 0.3 mg/kg may be administered IV every 2 to 3 hours or IM every 4 to 5 hours to maintain a target plasma concentration between 2 and 4 ng/mL in guinea pigs. Hydromorphone had high bioavailability after IM administration. Further research is necessary to evaluate the effects of other doses and administration routes and the analgesic effects of hydromorphone in guinea pigs.

Ultrastructural Analysis and ABR Alterations in the Cochlear Hair-cells Following Aminoglycosides Administration in Guinea Pig

Ultrastructural Analysis and ABR Alterations in the Cochlear Hair-cells Following Aminoglycosides Administration in Guinea Pig

Evaluating the Pharmacodynamics and Protective Efficacy of Catalytic Bioscavenger following Subcutaneous Administration in Guinea Pigs

Previous studies determined the guinea pig was a viableanimal model for evaluating subcutaneous (s.c.)injection as an alternative route of administration of catalytic Bioscavengers:enzymes designed to render nerve agents non‐toxic in systemic circulation following exposure. Recent studies have focused on evaluating the pharmacodynamics (PD) and protective efficacy (PE) of the lead bioscavenger candidate, organophosphorus hydrolase (OPH) variant, YT, as both unmodified and modified (PEGylated) versions of the enzyme. A comparative study was conducted with YT and three progressively sized PEG‐YT variants (934, 935, and 936) following a single bolus s.c. dose (5 mg/kg). Bioavailability increased linearly with molecular size such that the largest sized PEG‐YT variant, 936, afforded the highest bioavailability, thus promoting 936 to subsequent PD and PEstudies. Dose dependence on bioavailability was also examined via three cohorts of guinea pigs receiving doses (5, 15, 20 mg/kg) of either YT or 936 in which a linear dose response was also found. Guinea pigs receiving either YT or 936 (5 mg/kg) via intramuscular (i.m.)or s.c. routes had superimposable PD profiles regardless of route, suggesting an identical absorption pathway for the drugs. Protective efficacy was also evaluated by exposing the animals to 2xLD50 of sarin (GB) 7 dayspost‐enzyme administration; only the animals receiving 936 (i.m. and s.c.) survived 24 hours post‐exposure. Periodic s.c. dosing strategies were also evaluated with 936 in which three injections were administered either 2 or 24 hours apart for a total dose of 15 mg/kg followed by a protective efficacy assessment 8 days post‐administration. Overall these data support the use of s.c. injection as a practical route of administration for catalytic bioscavenger with PE Gylation, synergistically enhancing both bioavailability and extending drug half‐life in circulation.Support or Funding InformationThe views expressed in this abstract are those of the author(s) and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. The experimental protocol was approved by the Animal Care and Use Committee at the United States Army Medical Research Institute of ChemicalDefense and all procedures were conducted in accordance with the principlesstated in the Guide for the Care and Use of Laboratory Animals and the AnimalWelfare Act of 1966 (P.L. 89–544), as amended. This work was supported by the Defense Threat Reduction Agency‐Joint Science and Technology Office, MedicalS&T Division.*Thisresearch was supported in part by an appointment to the Postgraduate ResearchParticipation Program at the U.S. Army Medical Research Institute of ChemicalDefense administered by the Oak Ridge Institute for Science and Educationthrough an interagency agreement between the U.S. Department of Energy and USAMRMC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pharmacokinetics of buprenorphine after intravenous and oral transmucosal administration in guinea pigs (Cavia porcellus).

OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study). PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.

The Effects of Experimental Intratympanic Steroid Administration on Organ of Corti Type 1 Spiral Ganglion.

Introduction It is unclear how effective is the intratympanic (IT) steroid treatment on organ of Corti type 1 spiral ganglion, its optimal dosage and frequency of administration. The effect of dexamethasone on cochlear functions in individuals with a normal hearing ability is also unknown. Objective The aim of this study was to evaluate, at the electrophysiological and ultrastructural levels, the effect of IT dexamethasone administration in guinea pigs with normal hearing on organ of Corti type 1 spiral ganglion. Methods A total of 20 guinea pigs ( n = 40 ears) whose hearing was detected to be normal by electrophysiological tests were included in the study and randomly divided into 6 groups. Four groups were considered study groups, while 2 groups were considered control groups. Dexamethasone was administered intratympanically in doses of 2 mg/mL and 4 mg/mL in the guinea pigs in the study groups. The animals in the control groups received physiological saline in equal doses as the study groups. All interventions were performed under general anesthesia, and the electrophysiological tests were repeated following the IT injections. Results No statistically significant differences were found among the groups when the IT injections were evaluated in terms of the electrophysiological measurements ( p > 0.05). The ultrastructural evaluation showed a cellular mitochondrial increase in the spiral ganglions of the cochlea in the groups in which dexamethasone was administered in a dose of 4 mg/mL. Conclusion According to the findings of this study, it can be suggested that the IT injection of dexamethasone is safe, and when applied in a dose of 4 mg/mL, it increases metabolic activity at the cellular level.

Tu1668 - Bitter Taste Receptors (TAS2RS) Regulate Gastric Accommodation Following Liquid Meal Administration in Guinea Pigs

Tu1668 - Bitter Taste Receptors (TAS2RS) Regulate Gastric Accommodation Following Liquid Meal Administration in Guinea Pigs

EVALUACIÓN in vivo DE Lactobacillus plantarum CON CARACTERÍSTICAS PROBIÓTICAS MEDIANTE QUÍMICA SANGUÍNEA, INMUNOHISTOQUÍMICA Y MICROSCOPIA ELECTRÓNICA EN Cavia porcellus

Health problems mainly the lack of a specific pharmacology, affect the production parameters and the profitability of productions guinea pig in the department of Narino. Which is why, new alternatives that promote cleaner production through the use of probiotic lactic acid bacteria (LAB) are raised. Therefore, the in vivo effect of L. plantarum administration in guinea pigs of alternative to antibiotics in two different diets was assessed. peptides by HPLC was determined in the supernatant, resistance to basic pH, analysis of zootechnical parameters, laboratory tests (Table hematic, blood chemistry, partial urine and stool) before and after administration to the further selected animals was analyzed effectiveness by colonization tests histopathology, histochemistry, immunohistochemistry and scanning electron microscopy. GPT and CA statistically significant differences between diets. Also different degrees of severity and type of injury in the intestinal tissues adherent bacteria was observed hairiness with Gram staining and scanning electron microscopy. The PAS was positive for all treatments and immunostaining was mild, moderate or severe depending on the intestinal segment.

Pro-inflammatory cytokines, IL-1β and TNF-α, produce persistent compromise in tonic immobility defensive behaviour in endotoxemia guinea-pigs.

Sepsis has been associated with acute behavioural changes in humans and rodents, which consists of a motivational state and an adaptive response that improve survival. However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (TI) defensive behaviour remains a literature gap. Our purposes were to characterize the TI defensive behaviour in endotoxemia guinea-pigs at acute phase and after recovery from the initial inflammatory challenge. Furthermore, we investigated whether peri-aqueductal grey matter (PAG) exists as a brain structure related to this behaviour and also pro-inflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β, act at this mesencephalic nucleus. Endotoxemia was induced by lipopolysaccharide (LPS) administration in guinea-pigs. The parameters evaluated included TI defensive behaviour, survival, cytokines production, as well as neuronal activation and apoptosis in the PAG. Endotoxemia guinea-pigs exhibited a reduction in the duration of TI episodes, starting at 2h after LPS administration and persisting throughout the experimental period evaluated over 7days. Moreover, endotoxemia increased the c-FOS immunoreactivity of neurones in the ventrolateral PAG (vlPAG), as well as the caspase-3 expression. The LPS microinjection into vlPAG reproduces the same compromise, that is a decrease in the duration of TI defensive behaviour, observed after the peripheral administration. The immunoneutralization against IL-1β and TNF-α into vlPAG reverts all the effects produced by peripheral LPS administration. Our findings confirm that vlPAG is an important brain structure involved in the behavioural alterations induced by endotoxemia, possibly changing the neuronal activity caused by pro-inflammatory cytokines produced peripherally.

Gentamicin administration on the stapes footplate causes greater hearing loss and vestibulotoxicity than round window administration in guinea pigs

Clinically, gentamicin has been used extensively to treat the debilitating symptoms of Mèniére's disease and is well known for its vestibulotoxic properties. Until recently, it was widely accepted that the round window membrane (RWM) was the primary entry route into the inner ear following intratympanic drug administration. In the current study, gentamicin was delivered to either the RWM or the stapes footplate of guinea pigs (GPs) to assess the associated hearing loss and histopathology associated with each procedure. Vestibulotoxicity of the utricular macula, saccular macula, and crista ampullaris in the posterior semicircular canal were assessed quantitatively with density counts of hair cells, supporting cells, and stereocilia in histological sections. Cochleotoxicity was assessed quantitatively by changes in threshold of auditory brainstem responses (ABR), along with hair cell and spiral ganglion cell counts in the basal and second turns of the cochlea. Animals receiving gentamicin applied to the stapes footplate exhibited markedly higher levels of hearing loss between 8 and 32 kHz, a greater reduction of outer hair cells in the basal turn of the cochlea and fewer normal type I cells in the utricle in the vestibule than those receiving gentamicin on the RWM or saline controls. This suggests that gentamicin more readily enters the ear when applied to the stapes footplate compared with RWM application. These data provide a potential explanation for why gentamicin preferentially ablates vestibular function while preserving hearing following transtympanic administration in humans.

The effect of systemic administration of desmopressin on cochlear function in guinea pigs

Conclusions: Systemic desmopressin (dDAVP) administration in guinea pigs for up to 2 weeks induced only minor or no significant changes in cochlear sensitivity, suggesting that other factors may be required to induce the cochlear dysfunction that is usually associated with endolymphatic hydrops. Objectives: To investigate the effects of chronic systemic administration of dDAVP, a synthetic analog of vasopressin, on cochlear sensitivity in guinea pigs. Methods: dDAVP was administered subcutaneously via a mini-osmotic pump, at a rate of 0.2 ng/kg/min (low-dose group) or 2.0 ng/kg/min (high-dose group) for up to 2 weeks. Cochlear responses (compound action potentials) and distortion product otoacoustic emissions (DPOAEs) were measured. Example specimens were scanned using X-ray micro-tomography (micro-CT). Results: Compared with the control group, the low-dose dDAVP group showed a significant threshold increase in response to a 2 kHz tone-burst after 2 weeks of treatment, and also a decrease in the amplitude of the DPOAE after 1 week of treatment. However, individual results were variable and the high-dose dDAVP group showed no significant change compared to the control group. In the micro-CT images, two of four ears in the low-dose group showed mild hydrops, but no hydrops was found in the three ears sampled from the high-dose group.

Temporal and spatial distribution of gentamicin in the peripheral vestibular system after transtympanic administration in guinea pigs

Background and objectiveTranstympanic administration of gentamicin is effective for treating patients with intractable vertigo. This study explored the spatial and temporal distribution of gentamicin in vestibular end-organs after transtympanic administration. MethodsThirty guinea pigs were transtympanically injected with gentamicin conjugated to Texas Red (GTTR) and their vestibular end-organs examined after various survival periods. Another 9 guinea pigs received GTTR at different doses. Nine animals received Texas Red only and served as controls. We used confocal microscopy to determine the cellular distribution of GTTR in semicircular canal cristae, as well as the utricular and saccular maculae. ResultsThe most intense GTTR labeling was present in the saccule compared to other vestibular end-organs. GTTR fluorescence was detected predominantly in type I hair cells, type II hair cells and transitional cells after a single transtympanic dose of GTTR (0.1 mg/ml, 0.05 ml), while only weak fluorescence was observed in non-sensory cells such as supporting cells, dark cells and lumenal epithelial cells. Transitional cells displayed intense GTTR fluorescence in the supra-nuclear regions 24 h after transtympanic injection that was retained for at least 4 weeks. A decreasing spatial gradient of GTTR fluorescence was observed sensory epithelial regions containing central type I to peripheral type I and then type II hair cells in the crista ampullaris, and from striolar to extra-striolar hair cells within the vestibular macula. GTTR fluorescence extended from being restricted to the apical cytoplasm at lower doses to the entire cell body of type I hair cells with increasing dose. GTTR fluorescence reached peak intensities for individual regions of interest within the cristae and maculae between 3 and 7 days after transtympanic injection. ConclusionThe saccular uptake of GTTR is greater than other vestibular end-organs after transtympanic injection in the semicircular canals.

Uptake of gentamicin by vestibular efferent neurons and superior olivary complex after transtympanic administration in guinea pigs

Transtympanic administration of gentamicin is a widely accepted and effective approach for treating patients with intractable vertigo. Previous studies have demonstrated the uptake, distribution and effects of gentamicin in peripheral vestibular and cochlear structures after transtympanic injection. However, little is known about whether transtympanically administered gentamicin is trafficked into more central auditory and vestibular structures and its effect on these structures. In this study, we used immunofluorescence to determine the distribution of gentamicin within the auditory and vestibular brainstem. We observed gentamicin immunolabeling bilaterally in the vestibular efferent neurons, and in the superior olivary complex, and ipsilaterally in the cochlear nucleus 24h after transtympanic administration of gentamicin, and that the drug could still be detected in these locations 30 days after injection. In contrast, no gentamicin labeling was detected in the vestibular nuclear complex. In the vestibular efferent neurons and superior olivary complex, gentamicin labeling was detected in the cytoplasm and cell processes, while in the cochlear nucleus gentamicin is mainly localized outside and adjacent to the cell bodies of neurons. Nerve fibers in cochlear nucleus, root of eighth nerve, as well as descending pathways from the superior olivary complex, are also immunolabeled with gentamicin continuously. Based on these data, we hypothesize that retrograde axonal transport of gentamicin is responsible for the distribution of gentamicin in these efferent nuclei including vestibular efferent neurons and superior olivary complex and anterograde axonal transport into the ipsilateral cochlear nucleus.

The determination of beta-substituted glutarimides in blood: time-concentration curves after intravenous administration of two barbiturate antagonists.

Abstract A simple and rapid spectrophotometric procedure has been developed which is capable of estimating 2 mg. per cent of β-substituted glutarimides in blood with an accuracy of 90 per cent. Within 10 minutes of intravenous administration in guinea pigs 90 per cent of two barbiturate antagonists, β-methyl-β-ethyl glutarimide and β-spirocyclo-pentane glutarimide were removed from blood. Some discussion follows on whether the compounds were rapidly metabolised in blood or distributed evenly throughout the body tissues. The phase of rapid removal is followed by a period of moderately slow removal, apparently due to excretion.

Evidence-Based Modification of Intratympanic Gentamicin Injections in Patients With Intractable Vertigo

To compare the cochlear distribution of low-dose fluorescent gentamicin after intra-tympanic administration in guinea pig (GPs) with clinical data of low dose intra-tympanic gentamicin in patients with intractable vertigo. Purified gentamicin-Texas Red (GTTR) was injected intratympanically into GPs and the cochlear distribution and time course of GTTR fluorescence in outer hair cells (OHCs) was determined using confocal microscopy. GTTR was rapidly taken up by OHCs, particularly in the subcuticular zone. GTTR was distributed in the cochlea in a decreasing baso-apical gradient, and was retained within OHCs without significant decrease in fluorescence until 4 weeks after injection. OHCs rapidly take up GTTR after intra-tympanic administration with slow clearance. A modified low-dose titration intratympanic approach was applied to patients with intractable Ménière's Disease (MD) based on our animal data and the clinical outcome was followed. After the modified intratympanic injections for MD patients, vertigo control was achieved in 89% patients, with hearing deterioration identified in 16% patients. The 3-week interval titration injection technique thereby had a relatively high vertigo control rate with a low risk of hearing loss, and is a viable alternative to other intratympanic injection protocols.

Asian sand dust aggravates allergic rhinitis in guinea pigs induced by Japanese cedar pollen

Asian sand dust (ASD) contains microbial materials, sulfate (SO42−), and nitrate (NO3−), and is derived from air pollutants in East China. ASD reportedly causes adverse respiratory health effects; a case in point is aggravated allergen-associated experimental lung eosinophilia. Guinea pigs were administered normal saline (control), ASD (0.3 mg/animal), ASD (0.6 mg/animal), Japanese cedar pollen (JCP) (0.2 mg/kg body weight), JCP + ASD (0.3 mg/animal), or JCP + ASD (0.6 mg/animal), into their nasal cavities at seven weekly intervals. The number of sneezes, amount of nasal secretions, and nasal obstructing response were measured as indices of nasal responses. Total immunoglobulin E (IgE) antibodies in serum and the number of eosinophils, histamine, and arachidonic acid metabolites in nasal cavity lavage fluids (NCLF) were also measured. ASD enhanced the JCP-associated nasal obstructing response, but not the number of sneezes or amount of nasal secretions. ASD enhanced JCP-associated cysteinyl leukotrienes (C4, D4, E4) and histamine production in NCLF. ASD augmented the number of eosinophils in NCLF and total IgE in serum induced by JCP. ASD enhanced eosinophil recruitment in the nasal mucosa, and goblet cell proliferation in the nasal epithelium induced by JCP. These results suggest that ASD enhances the nasal allergic reaction induced by repeated JCP administration in guinea pigs.