Emetic Action of Nitrogen Mustard (Mechlorethamine Hydrochloride) in Dogs and Cats

1958 ◽  
Vol 192 (2) ◽  
pp. 410-416 ◽  
Author(s):  
H. L. Borison ◽  
E. D. Brand ◽  
R. K. Orkand
Keyword(s):  
Spinal Cord ◽  
Response Curve ◽  
Species Differences ◽  
Nitrogen Mustard ◽  
Amine Hydrochloride ◽  
Dorsal Rhizotomy ◽  
Chemoreceptor Trigger Zone ◽  
Spinal Segments ◽  
Trigger Zone ◽  
Frontal Lobectomy

The early emetic response (within 4 hr.) after intravenous injection of the nitrogen mustard, methyl-bis (beta-chlorethyl) amine hydrochloride, was compared in dogs and cats. The emetic effect of the drug in dogs differed from that in cats in the following respects: a) the dose of 0.5 mg/kg was uniformly effective in dogs whereas the lowest uniformly effective dose in cats was 5.0 mg/kg. b) Dogs were completely protected against the emetic effect, up to 10.0 mg/kg, by chronic ablation of the medullary emetic chemoreceptor trigger zone (CT zone), whereas cats were not. Cats were completely protected against the emetic effect by abdominal deafferentation accomplished by transthoracic vagotomy in combination with either spinal cord transection at T4 or dorsal rhizotomy of spinal segments T5 to T10. The dose-response curve for emesis after nitrogen mustard in the cat was shifted towards a higher dose level by acute decerebration. A forebrain facilitatory role was further supported by a protective effect, against the mustard-induced vomiting, afforded by chronic frontal lobectomy in the cat. Attention is directed to the similarity in emetic actions of nitrogen mustard and x-radiation, including parallel species differences between dogs and cats.

Role of medullary emetic chemoreceptor trigger zone (CT zone) in postnephrectomy vomiting in dogs

1959 ◽  
Vol 197 (4) ◽  
pp. 850-852 ◽  
Author(s):  
H. L. Borison ◽  
L. M. Hebertson
Keyword(s):  
Spinal Cord ◽  
Serum Sodium ◽  
Guanidine Hydrochloride ◽  
Rapid Decline ◽  
Bilateral Nephrectomy ◽  
Sodium Potassium ◽  
Chemoreceptor Trigger Zone ◽  
Serum Chloride ◽  
Trigger Zone

Latencies for vomiting following bilateral nephrectomy in control dogs, after gut denervation by transthoracic vagotomy and spinal cord transection at T4, and after ineffective ablation of the CT zone, were all within a range of 16–48 hours. By contrast, in dogs with effective lesions of the CT zone, the latency for vomiting after nephrectomy was prolonged to a range of 54–147 hours and two dogs died after 5 and 6 days, respectively, without vomiting. Chlorpromazine and morphine did not prolong the latency for vomiting after nephrectomy. Guanidine hydrochloride, 75 mg/kg i.v., evoked vomiting in all of seven control dogs, but only in one of nine dogs with effective lesions of the CT zone. Except for a more rapid decline of serum chloride in control dogs, serum sodium, potassium, bicarbonate and blood urea nitrogen followed the same pattern after nephrectomy in control and CT-zone ablated dogs.

The Effect of Superdisintegrants on the Dissolution of Promethazine. HCl Fast Dissolving Tablets

2010 ◽  
Vol 3 (1) ◽  
pp. 867-871
Author(s):  
Ganesh kumar Gudas ◽  
Manasa B ◽  
Senthil Kumaran K ◽  
Rajesham V V ◽  
Kiran Kumar S ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Angle Of Repose ◽  
Content Uniformity ◽  
Disintegration Time ◽  
Enhanced Dissolution ◽  
Weight Variation ◽  
Compressibility Index ◽  
Chemoreceptor Trigger Zone ◽  
Trigger Zone ◽  
Standard Limit

Promethazine.HCl is a potent anti-emetic. The central antimuscarinic actions of antihistamines are probably responsible for their anti-emetic effects. Promethazine is also believed to inhibit the medullary chemoreceptor trigger zone, and antagonize apomorphine -induced vomiting. Fast dissolving tablets of Promethazine.HCl were prepared using five superdisintegrants viz; sodium starch glycolate, crospovidone, croscarmellose, L-HPC and pregelatinised starch. The precompression blend was tested for angle of repose, bulk density, tapped density, compressibility index and Hausner’s ratio. The tablets were evaluated for weight variation, hardness, friability, disintegration time (1 min), dissolution rate, content uniformity, and were found to be within standard limit. It was concluded that the fast dissolving tablets with proper hardness, rapidly disintegrating with enhanced dissolution can be made using selected superdisintegrants. Among the different formulations of Promethazine.HCl was prepared and studied and the formulation S2 containing crospovidone, mannitol and microcrystalline cellulose combination was found to be the fast dissolving formulation. In the present study an attempt has been made to prepare fast dissolving tablets of Promethazine.HCl, by using different superdisintegrants with enhanced disintegration and dissolution rate. 

scholarly journals Commissural Interneurons in Rhythm Generation and Intersegmental Coupling in the Lamprey Spinal Cord

1999 ◽  
Vol 81 (5) ◽  
pp. 2037-2045 ◽  
Author(s):  
James T. Buchanan
Keyword(s):  
Spinal Cord ◽  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Rhythmic Activity ◽  
Ventral Root ◽  
Rhythm Generation ◽  
Spinal Segment ◽  
Spinal Segments ◽  
Autocorrelation Method

Commissural interneurons in rhythm generation and intersegmental coupling in the lamprey spinal cord. To test the necessity of spinal commissural interneurons in the generation of the swim rhythm in lamprey, longitudinal midline cuts of the isolated spinal cord preparation were made. Fictive swimming was then induced by bath perfusion with an excitatory amino acid while recording ventral root activity. When the spinal cord preparation was cut completely along the midline into two lateral hemicords, the rhythmic activity of fictive swimming was lost, usually replaced with continuous ventral root spiking. The loss of the fictive swim rhythm was not due to nonspecific damage produced by the cut because rhythmic activity was present in split regions of spinal cord when the split region was still attached to intact cord. The quality of this persistent rhythmic activity, quantified with an autocorrelation method, declined with the distance of the split spinal segment from the remaining intact spinal cord. The deterioration of the rhythm was characterized by a lengthening of burst durations and a shortening of the interburst silent phases. This pattern of deterioration suggests a loss of rhythmic inhibitory inputs. The same pattern of rhythm deterioration was seen in preparations with the rostral end of the spinal cord cut compared with those with the caudal end cut. The results of this study indicate that commissural interneurons are necessary for the generation of the swimming rhythm in the lamprey spinal cord, and the characteristic loss of the silent interburst phases of the swimming rhythm is consistent with a loss of inhibitory commissural interneurons. The results also suggest that both descending and ascending commissural interneurons are important in the generation of the swimming rhythm. The swim rhythm that persists in the split cord while still attached to an intact portion of spinal cord is thus imposed by interneurons projecting from the intact region of cord into the split region. These projections are functionally short because rhythmic activity was lost within approximately five spinal segments from the intact region of spinal cord.

scholarly journals Nausea and the Brain: The Chemoreceptor Trigger Zone Enters the Molecular Age

Neuron ◽  
2021 ◽  
Vol 109 (3) ◽  
pp. 391-393
Author(s):  
Wenfei Han ◽  
Ivan E. de Araujo
Keyword(s):  
Chemoreceptor Trigger Zone ◽  
Trigger Zone ◽  
The Brain

Species differences in the distribution and coexistence ratio of serotonin and substance P in the monkey, cat, rat and chick spinal cord

1991 ◽  
Vol 132 (2) ◽  
pp. 155-158 ◽  
Author(s):  
Nobuo Okado ◽  
Mutsumi Matsukawa ◽  
Shinobu Noritake ◽  
Shigeru Ozaki ◽  
Shun Hamada ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Species Differences ◽  
Chick Spinal Cord

Spinal stimulation to locate preganglionic neurons controlling the kidney, spleen, or intestine

1992 ◽  
Vol 263 (4) ◽  
pp. H1026-H1033 ◽  
Author(s):  
R. B. Taylor ◽  
L. C. Weaver
Keyword(s):  
Spinal Cord ◽  
Sympathetic Outflow ◽  
Renal Nerve ◽  
Homocysteic Acid ◽  
Sympathetic Control ◽  
The Third ◽  
Preganglionic Neurons ◽  
Spinal Segments ◽  
Vascular Beds ◽  
Nerve Discharge

The organization of sympathetic preganglionic neurons may be a substrate for selective control of sympathetic outflow to different vascular beds. This study was done to determine the spinal segments containing preganglionic neurons controlling discharge of renal, splenic, and mesenteric postganglionic nerves. In urethan-anesthetized rats, preganglionic neurons were stimulated by microinjecting D,L-homocysteic acid (3 nl, 0.17 M) into the lateral gray matter of the third thoracic (T3) to the fourth lumbar (L4) spinal segments. Responses from all three nerves could be elicited from segments T4-T13. The greatest increases in renal nerve discharge were evoked from segments T8-T12, the largest increase of 59 +/- 9% elicited from T10. Increases in splenic and mesenteric nerve discharge were smaller and were evoked more uniformly from T4-L3. The largest increases in discharge of splenic and mesenteric nerves were 19 +/- 5% (from T5) and 26 +/- 4% (from T10), respectively. The widely overlapping spinal cord segments controlling these three organs suggest that location of the preganglionic neurons in different spinal segments is not part of the mechanism for selective sympathetic control. However, the larger renal nerve responses demonstrate that sympathetic output to these organs can be differentiated at the level of the spinal cord.

Experimental Spinal Cord Injury: Spatiotemporal Characterization of Elemental Concentrations and Water Contents in Axons and Neuroglia

1999 ◽  
Vol 82 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
Richard M. LoPachin ◽  
Christopher L. Gaughan ◽  
Ellen J. Lehning ◽  
Yoshiro Kaneko ◽  
Thomas M. Kelly ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Water Content ◽  
Severely Injured ◽  
Channel Blockade ◽  
Compression Injury ◽  
Ion Distribution ◽  
Elemental Concentrations ◽  
Cord Injury ◽  
Spinal Segments

To examine the role of axonal ion deregulation in acute spinal cord injury (SCI), white matter strips from guinea pig spinal cord were incubated in vitro and were subjected to graded focal compression injury. At several postinjury times, spinal segments were removed from incubation and rapidly frozen. X-ray microanalysis was used to measure percent water and dry weight elemental concentrations (mmol/kg) of Na, P, Cl, K, Ca, and Mg in selected morphological compartments of myelinated axons and neuroglia from spinal cord cryosections. As an index of axon function, compound action potentials (CAP) were measured before compression and at several times thereafter. Axons and mitochondria in epicenter of severely compressed spinal segments exhibited early (5 min) increases in mean Na and decreases in K and Mg concentrations. These elemental changes were correlated to a significant reduction in CAP amplitude. At later postcompression times (15 and 60 min), elemental changes progressed and were accompanied by alterations in compartmental water content and increases in mean Ca. Swollen axons were evident at all postinjury times and were characterized by marked element and water deregulation. Neuroglia and myelin in severely injured epicenter also exhibited significant disruptions. In shoulder areas (adjacent to epicenter) of severely injured spinal strips, axons and mitochondria exhibited modest increases in mean Na in conjunction with decreases in K, Mg, and water content. Following moderate compression injury to spinal strips, epicenter axons exhibited early (10 min postinjury) element and water deregulation that eventually recovered to near control values (60 min postinjury). Na+ channel blockade by tetrodotoxin (TTX, 1 μM) perfusion initiated 5 min after severe crush diminished both K loss and the accumulation of Na, Cl, and Ca in epicenter axons and neuroglia, whereas in shoulder regions TTX perfusion completely prevented subcellular elemental deregulation. TTX perfusion also reduced Na entry in swollen axons but did not affect K loss or Ca gain. Thus graded compression injury of spinal cord produced subcellular elemental deregulation in axons and neuroglia that correlated with the onset of impaired electrophysiological function and neuropathological alterations. This suggests that the mechanism of acute SCI-induced structural and functional deficits are mediated by disruption of subcellular ion distribution. The ability of TTX to reduce elemental deregulation in compression-injured axons and neuroglia implicates a significant pathophysiological role for Na+ influx in SCI and suggests Na+ channel blockade as a pharmacotherapeutic strategy.

scholarly journals Neuromedin U receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Khaled Al-hosaini ◽  
Stephen R. Bloom ◽  
Joseph Hedrick ◽  
Andrew Howard ◽  
Preeti Jethwa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Amino Acid ◽  
Species Differences ◽  
Fetal Liver ◽  
Single Gene ◽  
Acid Product ◽  
Amino Acid Peptide ◽  
Upper Gastrointestinal ◽  
Sole Product

Neuromedin U receptors (provisional nomenclature as recommended by NC-IUPHAR [29]) are activated by the endogenous 25 amino acid peptide neuromedin U (neuromedin U-25, NmU-25), a peptide originally isolated from pig spinal cord [90]. In humans, NmU-25 appears to be the sole product of a precursor gene (NMU, P48645) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (neuromedin S-33) has also been identified as an endogenous agonist [95]. NmS-33 is, as its name suggests, a 33 amino-acid product of a precursor protein derived from a single gene and contains an amidated C-terminal heptapeptide identical to NmU. NmS-33 appears to activate NMU receptors with equivalent potency to NmU-25.

Development of specific muscle and cutaneous sensory projections in cultured segments of spinal cord

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1315-1323 ◽  
Author(s):  
K. Sharma ◽  
Z. Korade ◽  
E. Frank
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Muscle Afferents ◽  
Cutaneous Afferents ◽  
In Ovo ◽  
Sensory Afferents ◽  
Chicken Embryos ◽  
Sensory Projections ◽  
Spinal Segments ◽  
Horn Development

Development of sensory projections was studied in cultured spinal segments with attached dorsal root ganglia. In spinal segments from stage 30 (E6.5) and older chicken embryos, prelabeled muscle and cutaneous afferents established appropriate projections. Cutaneous afferents terminated solely within the dorsolateral laminae, whereas some muscle afferents (presumably Ia afferents) projected ventrally towards motoneurons. Development of appropriate projections suggests that sufficient cues are preserved in spinal segments to support the formation of modality-specific sensory projections. Further, because these projections developed in the absence of muscle or skin, these results show that the continued presence of peripheral targets is not required for the formation of specific central projections after stage 29 (E6.0). Development of the dorsal horn in cultured spinal segments was assessed using the dorsal midline as a marker. In ovo, this midline structure appears at stage 29. Lack of midline formation in stage 28 and 29 cultured spinal segments suggests that the development of the dorsal horn is arrested in this preparation. This is consistent with earlier reports suggesting that dorsal horn development may be dependent on factors outside the spinal cord. Because dorsal horn development is blocked in cultured spinal segments, this preparation makes it possible to study the consequences of premature ingrowth of sensory axons into the spinal cord. In chicken embryos sensory afferents reach the spinal cord at stage 25 (E4.5) but do not arborize within the gray matter until stage 30. During this period dorsal horn cells are still being generated. In spinal segments, only those segments that have developed a midline at the time of culture support the formation of midline at the time of culture support the formation of specific sensory projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional Specificity of Spinal Cord Segments in the Control of Limb Movements

Development ◽  
1963 ◽  
Vol 11 (2) ◽  
pp. 431-444
Author(s):  
George Székely
Keyword(s):  
Spinal Cord ◽  
Limb Movement ◽  
Limb Movements ◽  
Functional Specificity ◽  
Ample Evidence ◽  
Embryonic Life ◽  
Spinal Segments ◽  
Supernumerary Limbs ◽  
Experimental Approaches ◽  
Central Apparatus

There is ample evidence that limbs innervated by spinal segments which normally do not supply limbs, do not exhibit co-ordinated movements (Detwiler, 1920). Nerve formation under such circumstances seems to be fairly normal, i.e. essentially characteristic for the innervated limb (Detwiler, 1920; Piatt, 1956), so that failure of nerve formation and of re-innervation of the muscles cannot be blamed for the result. It is more probable that the limbinnervating segments of the spinal cord: the brachial (segments 3, 4, 5 in the newt) and the lumbo-sacral (segments 16, 17, 18) might alone possess a central apparatus determined in early embryonic life with the capacity to innervate and move limbs in a co-ordinated manner (Detwiler, 1936; Weiss, 1955; Rogers, 1934). Although some experimental approaches (Moyer, 1943, Piatt, 1957) were unsuccessful, it is obvious that this problem could best be investigated by transplanting brachial or lumbo-sacral segments into the place of the thoracic segments, and by additionally implanting at the same level supernumerary limbs to be innervated by the grafted cord segments that might contain the postulated specific apparatus for co-ordinated limb movement.

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