Instillation Of Mustard Oil Research Articles

Otomycosis and its Predisposing Factors in Out-Patient Department of Otorhinolaryngology in a Tertiary Care Center

Introduction: Otomycosis is a fungal infection of external auditory canal frequently encountered by otorhinolaryngologists. It causes discomfort to patients with varied symptoms of pruritus, otorrhea, aural fullness and earache. People with a habit of using unnecessary ear drops, cleaning ear with unsterilized objects and those who use mustard oil are all prone to otomycosis. This study aims to find out the association between otomycosis and its predisposing factors. Methods: This study was undertaken in the Department of Otorhinolaryngology of a tertiary hospital from March 2018 to February 2019 and a total of 300 clinically diagnosed cases of otomycosis were enrolled for the study. Results: The mean age ±SD of the patients was 37.7 ± 18.8 years. Females (n=172, 57.3%) were more prone to otomycosis than males (n=128, 42.7%). The most common presenting symptom was pruritus only (n=95, 31.7%) with unilateral involvement being more common. The most common predisposing factor was mustard oil instillation (n=124, 41.3%). Aspergillus niger was the most common fungus causing otomycosis in this study (n=104, 34.7%). Positive fungal cultures were observed in 285 specimens (95%). The fungal growth (n=285) was high in patients with the history of instilling mustard oil (42.8%) into the ear, 34.0% in topical steroid containing ear drops and 23.2% in self-cleaning group. Conclusion: Otomycosis is common in people using unnecessary steroid containing ear drops, cleaning ear with unsterilized objects and instillation of mustard oil.

Otomycosis in a Rural Community Attending a Tertiary Care Hospital: Assessment of Risk Factors and Identification of Fungal and Bacterial Agents.

Otomycosis is one of the frequently encountered fungal infections of external auditory canal, commonly seen in tropical and subtropical regions of the world. Various host (local, systemic) and environmental factors can predispose a person to otomycosis. Although clinical presentations along with otoscopic findings of the patients are well suggestive of fungal infection, proper identification of causative agents is mandatory in order to prevent recurrences and complications. To define the aetiology of clinically diagnosed otomycosis in rural population, to derive association of risk factors with otomycosis, to isolate and identify fungal and bacterial agents and to analyze the association between them. A prospective study was conducted in the Department of Microbiology and Department of Ear, Nose and Throat (ENT), SGT hospital over eight months period. A total of 350 consecutive patients of more than five years of age with clinical diagnosis of otomycosis were included in the study. Demographic profile, predisposing factors, presenting complaints and clinical findings of clinically diagnosed patients were evaluated and analyzed. Samples were collected, transported and evaluated by both direct examination and culture method for bacteriological and mycological examination. Male to female ratio in study participants was 1.3:1. Mycological examination yielded 346 fungal isolates in 310 samples from a total of 350 clinically diagnosed cases of otomycosis. Self cleaning, instillation of mustard oil and use of ear drops appeared to be common predisposing factors in otomycosis. Significant association was observed between these practices and otomycosis. Aspergillus species was the predominant fungi followed by Candida spp., Penicillium, Mucor and Trichophyton mentagrophyte. 11% of the cases were found to have mixed fungal and bacterial infections. The present study highlights the highest isolation of Aspergillus complex in cases of clinically diagnosed otomycosis in a rural community with higher practice of self cleaning and using home remedies and eardrops to get relief from sensation of blocked ear and itching.

Novel orally available salvinorin A analog PR-38 protects against experimental colitis and reduces abdominal pain in mice by interaction with opioid and cannabinoid receptors

BackgroundSalvinorin A (SA) is a potent anti-inflammatory diterpene isolated from the Mexican plant S. divinorum. Recently we showed that the novel SA analog, PR-38 has an inhibitory effect on mouse gastrointestinal (GI) motility mediated by opioid and cannabinoid (CB) receptors. The aim of the study was to characterize possible anti-inflammatory and antinociceptive action of PR-38 in the mouse GI tract. MethodsMacro- and microscopic colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and per os (p.o.) administration of PR-38 in the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, MOP, KOP and CB1 protein expression was determined using Western blot analysis of mouse colon samples. The antinociceptive effect of PR-38 was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). ResultsThe i.p. (10mg/kg, twice daily), i.c. (10mg/kg, twice daily) and p.o. (20mg/kg, once daily) administration of PR-38 significantly attenuated TNBS- and DSS-induced colitis in mice. The effect of PR-38 was partially blocked by the KOP antagonist nor-binaltorphimine and CB1 antagonist AM 251. Western blot analysis showed a significant increase of MOP, KOP and CB1 receptor expression during colonic inflammation, which was reversed to the control levels by the administration of PR-38. PR-38 significantly decreased the number of pain responses after i.c. instillation of MO in the TNBS-treated mice. ConclusionsOur results suggest that PR-38 has the potential to become a valuable anti-inflammatory and analgesic therapeutic for the treatment of GI inflammation.

Not a typical urinary tract infection: A case of urethritis due to an exogenous oil instillation in penile urethra of an infant

However, there are no reports of the exogenous oil instillation in penile urethra in infants or children. We report the first case of sterile urethritis caused as a result of cultural practicing of blowing oil into urethra of an infant.An 11-month-old male child was taken to the outpatient department of a tertiary care center of Central India with the complaints of increased frequency and excessive crying during micturition. There was no history of passing of loose stools, fever, and previous history of urinary tract infection or edema. There was no external gross deformity of the penis. Investigations revealed total leucocyte count of 5600/cumm (polymorphs 38%, lymphocytes 54%, monocytes 6%, and eosinophils 2%). Serum urea, creatinine, and electrolytes were within the normal limits. Urinalysis was also within normal limits except for the 40-50 white blood cells/high power field. Ultrasonogarphy of the abdomen was within normal limits. On detailed history taking from the parents it was admitted that mustard oil was instilled in the urethra of the infant. It was further admitted by the mother that this a common practice in their tribe to instill oil in urethra and blow it with mouth to relieve physiological phimosis in children. A diagnosis of sterile urethritis was made, and the parents were counseled to avoid such harmful customs. Patient was given a short course of paracetamol and prednisolone (1 mg/kg/day) for 5 days. A repeat urinalysis was done after a week which revealed no abnormality.Thus, in the present case, the urethritis was caused by the exogenous instillation of mustard oil and presented as sterile pyuria that is a common sign of intraurethral foreign body induced disorder.

Acute Uterine Irritation Provokes Colonic Motility via Transient Receptor Potential A1-dependent Spinal NR2B Phosphorylation in Rats

Patients with inflammatory gynecological/obstetrical problems often complain of irritable bowel syndrome. The authors examined whether acute uterus irritation reflexively provokes colonic motility in rat preparations. A modified colon manometry and striated abdominal muscle electromyogram activity in response to mustard oil (MO) instillation into the uterine horn were continuously recorded in anesthetized rats. The lumbosacral (L6-S1) dorsal horn was dissected to assess the level and the cellular location of phosphorylated NR2B subunit using Western blotting and immunofluorescence analysis, respectively. Finally, the uterine transient receptor potential A1 or spinal NR2B subunit was pharmacologically blocked to elucidate its roles. MO (0.1%, 0.2 ml) injected into the lower uterine horn dramatically provoked colonic hypermotility characterized by rhythmic colonic contractions (about 3-4 contractions per 10 min, n = 7) accompanied by synchronized electromyogram firing in the abdominal muscle (about 4-5 folds of control, n = 7). In addition to provoking colonic hypermotility, MO administration also up-regulated phosphorylated (about 2-3 folds of control, n = 7), but not total, NR2B expression in the dorsal horn neurons. Both intrathecal Ro 25-6981 (a selective NR2B subunit antagonist; 10 μM, 10 μl) and intrauterine HC-030031 (a selective transient receptor potential A1 receptor antagonist; 30 mg/kg, 0.2 ml) injected before the MO instillation attenuated the MO-induced colonic hypermotility and spinal NR2B phosphorylation. The comorbidity of gynecological/obstetrical and gastrointestinal problems is not coincidental but rather causal in nature, and clinicians should investigate for gynecological/urological diseases in the setting of bowel problems with no known pathological etiology.

Glucocorticoid mediates water avoidance stress-sensitized colon-bladder cross-talk via RSK2/PSD-95/NR2B in rats

Unexpected environmental and social stimuli could trigger stress. Although coping with stress is essential for survival, long-term stress impacts visceral functions, and therefore, it plays a role in the development and exacerbation of symptoms of gastrointestinal/urogenital disorders. The aim of this study is to characterize the role of corticosterone in stress-sensitized colon-bladder cross-talk, a phenomenon presumed to underlie the comorbidity of functional bowel and bladder disorders. Cystometry and protein/mRNA expression in the lumbosacral dorsal horn (L6-S1) in response to intracolonic mustard oil (MO) instillation were analyzed in female Wistar-Kyoto rats subjected to water avoidance stress (WAS; 1 h/day for 10 days) or sham stress (WAsham). Whereas it had no effect on baseline-voiding function, chronic stress upregulated plasma corticosterone concentration and dorsal horn spinal p90 ribosomal S6 kinase 2 (RSK2) protein/mRNA levels, and RSK2 immunoreactivity colocalized with NeuN-positive neurons. Intracolonic MO dose-dependently decreased intrercontraction intervals and threshold pressure, provoked spinal RSK2 and NR2B phosphorylation, and enhanced PSD-95-RSK2 and PSD-95-NR2B coupling. Intrathecal kaempferol (a RSK2 activation antagonist; 30 min before MO instillation), bilateral adrenalectomy (7 days prior the stress paradigm), and subcutaneous RU-38486 (a glucocorticoid receptor antagonist; 30 min daily before stress sessions), but not RU-28318 (a mineralocorticoid receptor antagonist), attenuated MO-induced bladder hyperactivity, protein phosphorylation, and protein-protein interactions in the WAS group. Our results suggest that stress-associated glucocorticoid release mediates WAS-dependent sensitization of colon-bladder cross-talk via the spinal RSK2/PSD-95/NR2B cascade and offer a possibility for developing pharmacological strategies for the treatment of stress-related pelvic pain.

Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors*

Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.

Effects of nociceptin/orphanin FQ on cross-organ sensitization in rat model with visceral hypersensitivity

Objective To investigate the effect of nociceptin/orphanin FQ (N/OFQ) on crossorgan sensitization and bladder function disorders in rat model with visceral hypersensitivity. Methods The model of cross-organ sensitization was induced by basic OVA-sensitization combined with colon mustard oil instillation in 44 female SD rats. All rats were then divided into control group (n= 14,infusion with 0.9% NaCl solution), model group (n= 14) and N/OFQ group (n= 16, infusion with N/OFQ). The anti-nociceptive effect of N/OFQ were evaluated by using the visceromotor response (VMR) to grade bladder distention (0. 5～2.0 ml, 20 s). Bladder function was evaluated with the cystometry by measuring voiding pressure and micturition frequency. Results The rats in model group had a significant increase of VMR response at 1.0 ml, 1.5 ml and 2.0 ml of pressure when compared to those in control group (P=0. 006,0. 015 and 0. 0331, respectively). However, N/OFQ treatment was able to reverse the increased VMR response in N/OFQ group at 1.5 ml and 2.0 ml of pressure (P=0. 016 and 0. 031, respectively). It was showed that mustard oil significantly reduced bladdervoiding pressure (P＜0. 01) and significantly increased micturition frequency (P＜0.01)in model group when compared to control group. The N/OFQ reversed the decrease of voiding pressure (P=0. 0038) and the increase of micturition frequency in N/OFQ group( P = 0. 001). Conclusions These findings indicate that the rat model of cross-organ sensitization was able to be established successfully by the basic OVA-sensitization combined with colon mustard oil instillation. N/OFQ has an antinociceptive effect on cross-organ hypersensitivity and attenuates changes in bladder urodynamic function. Key words: Analgesics; Pain; Nociceptin; Models, animal

PI3K modulates estrogen‐dependent facilitation of colon‐to‐urethra cross‐organ reflex sensitization in ovariectomized female rats

To determine the role of 17beta-estradiol and involvement of intracellular phosphatidylinositol-3-kinase signaling in cross-organ sensitization between the descending colon and the urethra, we analyzed urethra reflex activity and protein expressions in lumbosacral (L6-S2) spinal dorsal horn in response to mustard oil instillation into the descending colon in ovariectomized female rats. When compared with vehicle solution, intracolonic mustard oil sensitized the NMDA receptor NR2B subunit-dependent reflex activity and increased expression levels of phosphorylated Akt (pAkt) and phosphorylated NR2B (pNR2B) in dorsal horn. Facilitation of reflex sensitization and increases in protein expressions of pAkt and pNR2B in dorsal horn were induced after pre-treatment with a subcutaneous injection of 17beta-estradiol (5 microg/kg), 6 h ahead of time, when compared with vehicle solution. This phenomenon was reversed both by intrathecal pre-treatment with ICI 182780 (0.25 mg/kg, i.t.) and LY294002 (50 mg/kg, i.t.). Immunoprecipitation of dorsal horn tissue revealed a protein-protein interaction between pAkt and pNR2B increases, 6 h following the subcutaneous 17beta-estradiol when compared with vehicle injections. Results indicate 17beta-estradiol may activate the phosphatidylinositol-3-kinase cascade, which subsequently phosphorylates the NR2B subunit, via spinal estrogen receptors ERalpha/ERbeta, to facilitate NMDA-dependent cross-organ sensitization, which is presumed to underlie pelvic viscero-visceral referred pain.

Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B

Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in spinal pain-related neural plasticity has been identified. To test whether Src-family non-receptor tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor (NMDAR) NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate cross-organ sensitization between the colon and the urethra, external urethra sphincter electromyogram activity evoked by pelvic nerve stimulation and protein expression in the lumbosacral (L6-S2) dorsal horn were studied before and after intracolonic mustard oil (MO) instillation. We found MO instillation produced colon-urethra reflex sensitization along with an upregulation of endogenous ephrinB2 expression as well as phosphorylation of EphB 1/2, Src-family kinase, and NR2B tyrosine residues. Intrathecal immunoglobulin fusion protein of EphB1 and EphB2 as well as PP2 reversed the reflex sensitization and NR2B phosphorylation caused by MO. All these results suggest that EphBR-ephrinB interactions, which provoke Src-family kinase-dependent NMDAR NR2B phosphorylation at the lumbosacral spinal cord level, are involved in cross-organ sensitization, contributing to the development of viscero-visceral referred pain between the bowel and the urethra.

Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic–urethra reflex activity in rats

We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N-methyl- d-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ reflex sensitization caused by colon irritation. The external urethral sphincter electromyogram (EUSE) reflex activity evoked by the pelvic afferent nerve test stimulation (TS, 1 stimulation/30 s) and protein expression in the spinal cord and dorsal root ganglion tissue (T13-L2 and L6-S2 ipsilateral to the stimulation) in response to colon mustard oil (MO) instillation were tested in anesthetized rats. When compared with a baseline reflex activity with a single action potential evoked by the TS before the administration of test agents, MO instillation into the descending colon sensitized the evoked activity characterized by elongated firing in the reflex activity in association with increased protein levels of Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the spinal cord tissue. Both cross-organ reflex sensitization and increments in protein expression were reversed by intra-colonic pretreatments with ruthenium red (a non-selective transient receptor potential vanilloid, TRPV, antagonist), capsaizepine (a TRPV 1-selective antagonist), lidocaine (a nerve conduction blocker) as well as by the intra-thecal pretreatment with APV (a NRMDR antagonist) Co-101244 (a NR2B-selective antagonist) and roscovitine (a Cdk5 antagonist). Moreover, compared with the control group, both the increase in pNR2B and the cross-organ reflex sensitization were attenuated in the si-RNA of NR2B rats. All these results suggested that Cdk-dependent NMDAR NR2B subunit phosphorylation mediates the development of cross-organ pelvic–urethra reflex sensitization caused by acute colon irritation which could possibly underlie the high concurrence of pelvic pain syndrome with irritable bowel syndrome.

Estrogen rapidly modulates mustard oil-induced visceral hypersensitivity in conscious female rats: a role of CREB phosphorylation in spinal dorsal horn neurons

This study investigated the effect of sex hormones on mustard oil (MO)-induced visceral hypersensitivity in female rats and analyzed possible involved signaling pathways. Female rats, either intact or ovariectomized (OVX), were prepared for abdominal muscle electromyography in response to colorectal distension after intracolonic instillation of MO. The effect of MO intracolonic sensitization was evaluated in intact rats, OVX rats, and OVX rats pretreated with a single injection of 17beta-estradiol (E), progesterone (P), E+P, or vehicle. cAMP-responsive element-binding protein (CREB) and phosphorylated CREB (pCREB) were detected in the superficial dorsal horn of L6 and S1 in MO or mineral oil-treated OVX rats with/without colorectal distension and estrogen replacement. The distal colorectum was removed for histological evaluation of inflammatory severity in MO-treated intact or OVX rats. The MO-treated rats had significantly higher visceromotor reflex than controls (enhanced visceral hypersensitivity), whereas OVX eliminated this hypersensitivity. After a single injection of E or E+P, the rats rapidly restored MO-induced visceral hypersensitivity within 2 h. Estrogen also rapidly induced a dose-dependent increase in pCREB expression in the superficial dorsal horn neurons in MO-treated, but not mineral oil-treated, OVX rats. The present study suggests that estrogen can rapidly modulate visceral hypersensitivity induced by MO intracolonic instillation in conscious female rats, which may involve spinal activation of the cAMP response element-mediated gene induction pathway.

Effects of kappa opioid receptor-selective agonists on responses of pelvic nerve afferents to noxious colorectal distension.

The aim of this study was to examine the effects of kappa-opioid receptor selective agonists on responses of mechanosensitive afferent fibers in the pelvic nerve. Single-fiber recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root of the rat. A total of 572 afferent fibers in the S1 dorsal root were identified by electrical stimulation of the pelvic nerve; 252 (44%) responded to noxious colorectal distension (CRD; 80 mmHg). Of these 252 fibers that responded to CRD, 100 were studied further. All 100 fibers gave monotonic increases in firing to increasing pressures of CRD. Eighty-eight fibers had low thresholds for response (mean: 3 mmHg) and 12 fibers had high-thresholds for response (mean: 28 mmHg). Responses of 17 fibers also were tested after instillation of 5% mustard oil (MO) into the colon. The resting activity of 16/17 fibers significantly increased after MO instillation; 13 (77%) also exhibited sensitization of responses to graded CRD when tested 30 min after intracolonic MO instillation. The effects of kappa1-opioid receptor preferring agonists (U50,488H, U69,593 and U62,066), the kappa2-opioid receptor preferring agonist bremazocine, and the kappa3-opioid receptor preferring agonist naloxone benzoylhydrazone (nalBzoH) were tested on responses of 64 mechanosensitive afferent fibers to noxious CRD. All five agonists dose-dependently inhibited afferent fiber responses to noxious CRD. Doses producing inhibition to 50% of the control response to CRD did not differ among the five agonists, ranging from approximately 4 to 15 mg/kg. The effects of kappa1, kappa2, and kappa3 receptor agonists were attenuated by naloxone; two kappa-opioid receptor-selective antagonists were ineffective. There were no differences in the dose-response relationships of these drugs for fibers recorded from untreated and irritant-treated colons. Conduction velocities of the fibers remained unaffected after high doses of all tested agonists. In an in vitro study, U50,488 (10(-4) M) did not produce any significant change in the tension of colonic smooth muscle. These results document that responses of mechanosensitive pelvic nerve afferent fibers innervating the colon are inhibited by kappa-opioid receptor agonists having varying affinities for putative kappa-opioid receptor subtypes. The inhibitory effects of these drugs likely are mediated by an action at receptors associated with the afferent fibers. The receptor at which these effects are produced is kappa-opioid-like but clearly different from the kappa-opioid receptor characterized in the CNS and is perhaps an orphan receptor.

Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat.

A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of the rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated A delta fibers with a mean conduction velocity (CV) of 11.8 m/s and 124 (28%) were unmyelinated C fibers with mean CV of 1.9 m/s. Two hundred fifty-two fibers (57%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean CV; 1.9 m/s) and 144 were A delta fibers (mean CV; 8.2 m/s). Forty-nine UBD-sensitive fibers were further characterized; all gave monotonic increases in firing to increasing distending pressures. Thirty-six fibers (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 fibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Responses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 ml of 30% xylenes (n = 11) or 5% mustard oil (n = 4) into the bladder. The mean resting activity of 13 fibers significantly increased, and 7 fibers exhibited sensitization of responses to graded UBD 30 min after xylenes or mustard oil instillation. All 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid receptor agonists were tested on responses to noxious UBD (80 mmHg). Cumulative intraarterial doses of mu-opioid receptor agonists (morphine, 8 mg/kg, and fentanyl, 300 micrograms/kg) and of delta-opioid receptor agonists (DPDPE, 300 micrograms/kg, and SNC-80, 300 micrograms/kg) did not affect responses to noxious UBD. In contrast, cumulative 16 mg/kg intraarterial doses of the kappa-opioid receptor agonists U50,488H, U69,593 and U62,066 dose-dependently attenuated responses to noxious UBD. There were no differences in the dose-response relationships of these drugs on afferent fibers from untreated and xylenes- or mustard oil-treated urinary bladder. These results reveal that there is a greater proportion of UBD-sensitive fibers in the L6 dorsal root (57%) than in the S1 dorsal root of the rat (38%; a previous study). The attenuation of responses to UBD by kappa, but not mu or delta opioid receptor agonists suggests a potential use for peripherally acting kappa opioid receptor agonists in the control of urinary bladder pain.

Plasma extravasation in the rat urinary bladder following mechanical, electrical and chemical stimuli: evidence for a new population of chemosensitive primary sensory afferents

In the skin activation of unmyelinated primary afferents produces vasodilation and plasma extravasation. Here, using Evans blue dye leakage, we have quantitatively compared the ability of mechanical, chemical and electrical stimulation of afferents to produce extravasation in the urinary bladder of anaesthetized rats. Mechanical stimulation - a series of large active contractions of vesical smooth muscle induced by maintained distension - elicited no increase in extravasation compared to controls. In contrast, a similar period of electrical stimulation of nerves supplying the bladder, or chemical stimulation with intravesical instillation of mustard oil, produced high levels of extravasation. We conclude that afferents activated during distension and micturition contractions are different from those which produce extravasation. The latter may be important in pathophysiological cases such as inflammation of the urinary bladder.

Experimental use of enzymes for hyphemas and conjunctival hematomas.

In recent years there has accumulated considerable clinical and experimental evidence which shows that specific proteolytic enzymes can act as potent anti-inflammatory agents. <h3>Review of the Literature</h3> Gordon et al. (1957)¹induced inflammation in rabbits by the subconjunctival instillation of mustard oil. The intravenous administration of streptokinase-streptodornase preparations prior to the elicitation of the inflammation was shown to be effective in decreasing the severity of the reaction produced. When purified streptodornase was used alone, the reaction of the treated animals did not differ from that of the controls. When streptokinase purified by chromatography was employed, a definite inhibition of inflammation was observed. All effective antiedema concentrations of streptokinase produced demonstrable fibrinolytic responses in the rabbit. Doses of heparin sufficient to render the blood incoagulable during the experimental period were found to be ineffective in reducing the degree of edema produced. Consequently, it must be assumed that fibrin deposition is

Effect of streptokinase on mustard oil inflammation of the rabbit eye.

Intravenous or intramuscular streptokinase (SK), 100,000 or 500,000 u, respectively, was administered prior to the instillation of mustard oil in the rabbit eye. Comparison of the SK-treated animals with saline controls indicated that SK was effective in reducing this type of experimental inflammation.

The effect of local anaesthetics upon the conjunctivitis caused by mustard oil

Spiess1 and Ninian Bruce2 have shown that the oedema of the conjunctiva which can be produced by instilling mustard oil into the conjunctival sac of a rabbit, can be prevented by the instillation of 10 per cent. cocaine. Bruce interprets this action as being due to the inhibition of vasdilator axon reflexes to the capillaries and smaller arterioles, and he found that if the ophthalmic nerve was cut before applying mustard oil oedema could then be produced only during the period in which the vasodilator fibers were still undegenerated, and a sufficient time were allowed for the vasodilator nerves to degenerate completely before the mustard oil was applied, oedema did not result after the instillation of mustard oil. Bruce's results have been confirmed by Bardy.1In 1917 I2 was able to demonstrate the following facts : (1) That the application of epinephrin, producing a local vaso constriction of the conjunctival vessels, inhibited the development of the oedema, for about an hour, but that after the epinephr...