[Increased expression of SEMA5B in gastric adenocarcinoma predicts poor prognosis: a study based on TCGA data].

Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio(HR) of 1.042 (95%CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95%CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.

[Predictive factors of pathological complete response after neoadjuvant chemoradiotherapy for middle-low rectal cancer].

Objective: To explore the predictive factors of pathological complete response (pCR) after neoadjuvant chemoradiotherapy for middle-low rectal cancer. Methods: A case-control study was conducted. The inclusion criteria were as follows: (1) colonoscopy, digital examination or magnetic resonance imaging (MRI) showed a distance from the lower edge of the tumor to the dentate line of no more than 10 cm; (2) complete clinicopathological data were available; (3) preoperative biopsy revealed adenocarcinoma; (4) preoperative pelvic MRI or endorectal ultrasonography was performed; (5) no distant metastasis was found. Exclusion criteria: (1) preoperative radiotherapy and chemotherapy were not administrated according to the standard; (2) simultaneous multiple primary cancer and familial adenomatous polyposis were observed. According to the above criteria, clinicopathological data of 245 patients with middle-low rectal cancer undergoing preoperative neoadjuvant chemoradiotherapy in Changhai Hospital of Navy Medical University from January 2012 to December 2019 were retrospectively collected. Univariate analysis and multivariate logistic analysis were used to identify the clinical factors predicting pCR. pCR is defined as complete disappearance of cancer cells under the microscope in cancer specimens (including lymph nodes) after neoadjuvant chemoradiotherapy. Results: A total of 72 patients with pCR were enrolled in this study. Univariate analysis showed that preoperative T stage, tumor circumference, tumor morphology, carbohydrate antigen (CA) 19-9, interval between the end of neoadjuvant therapy and operation were associated with pCR (all P<0.05). The above 5 variables were included in multivariate logistic analysis and the results revealed that the T stage (OR=5.743, 95% CI: 2.416-13.648, P<0.001), tumor circumference (OR=7.754, 95% CI: 3.822-15.733, P<0.001), tumor morphology (OR=0.264, 95% CI: 0.089-0.786, P=0.017) and the interval between the end of neoadjuvant therapy and operation (OR=0.303, 95% CI: 0.147-0.625, P=0.001) were independent predictive factors of pCR, while CA 19-9 level was not an independent factor (OR=1.873, 95% CI:0.372-9.436, P=0.447). Conclusion: By knowing the clinical features of preoperative T stage, tumor circumference, tumor morphology and the interval between neoadjuvant chemoradiotherapy and operation, patients with higher likelyhood of pCR after neoadjuvant chemoradiotherapy may be identified.

LncRNA INHBA-AS1 promotes colorectal cancer cell proliferation by sponging miR-422a to increase AKT1 axis.

OBJECTIVE: In recent years, long non-coding RNAs (lncRNAs) have emerged for regulating the development, as well as progression in colorectal cancer (CRC), which assists in finding new targets for CRC treatment. A previous study indicated that INHBA-AS1 promotes oral squamous cell progression by sponging miR-143-3p. However, the exact function possessed by lncRNA INHBA-AS1 in CRC development remains unclear. PATIENTS AND METHODS: The expression level of INHBA-AS1 in CRC tissues and cell lines was determined by qRT-PCR. The functional role of INHBA-AS1 in CRC was investigated by a series of in vitro assays. RNA immunoprecipitation (RIP), bioinformatics analysis was utilized to explore the potential mechanisms of INHBA-AS1. RESULTS: The present study identified INHBA-AS1 as a kind of lncRNA with high expression in CRC tissues and cells. Functionally, NHBA-AS1 downregulation in CRC cells suppressed CRC cell proliferation as well as colony formability. Mechanistically, INHBA-AS1/miR-422a/AKT1 established the ceRNA network to regulate MMP-2, -7, -9 expressions that participated the modulation of CRC progression. CONCLUSIONS: In summary, LncRNA INHBA-AS1 contributes to CRC progression through AKT1 pathway, and provides a new mechanism to regulate CRC development, as well as a potential target for treating CRC.

Dietary threonine prevented stress-related mucosal diseases in rats.

Stress-related mucosal disease (SRMD), or stress ulceration, is a group of conditions ranging from stress-related superficial gastric mucosal damage to deep gastric ulcers that are primarily correlated with mucosal ischemia, and pharmacologic interventions that optimize tissue perfusion or preserve defensive mucus aim to decrease the occurrence of conditions, such as gastric acidity, or enhance gastric defenses. However, the identification of multifactorial pathogenesis may be effective in preventing SMRD, and the use of stress prophylaxis is generally preferred. Since threonine is a component in the polymerization and synthesis of gastric mucin and possibly enhanced defense actions and lignin may provide structural support for defense and antioxidative function, we hypothesized that dietary intake of threonine and/or lignin can enhance defense against SRMD. The water immersion-restraint stress (WIRS) was used in rats and additional groups were pretreated with threonine alone or the combination of threonine and lignin. Based on gross and microscopic evaluations, threonine alone or the combination of threonine and lignin, a natural antioxidant, significantly reduced the development of SRMD (P < 0.05). According to molecular explorations, the levels of inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1ß, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), all of which are mediators that play a significant role in controlling WIRS, significantly decreased in the groups pretreated with either threonine alone or the combination of threonine and lignin (P < 0.01). WIRS significantly increased apoptosis in the stomach. However, the apoptotic index significantly decreased with threonine pretreatment. According to periodic acid Schiff staining results, the expression of gastric mucin was significantly preserved in groups pretreated with threonine but remarkedly decreased in the WIRS group. The gastric heme oxygenase-1 levels significantly increased in the group treated with threonine. In conclusion, the dietary intake of threonine or the combination of threonine and lignin is effective in preventing SRMD.

Effects of ${\rm \small L}$-methionine on growth performance, carcass quality, feather traits, and small intestinal morphology of Pekin ducks compared with conventional ${\rm \small {DL}}$-methionine.

The research studied the effects of l-methionine (l-Met) on growth performance, carcass quality, feather traits, and small intestinal morphology of Pekin ducks compared with conventional dl-methionine (dl-Met). A total of 1080, 1-day-old male Pekin ducks were randomly allotted to 9 groups with 6 replicate pens of 20 birds each. During the starter phase (1 to 14 d), ducks were fed a basal diet (Met, 0.30%) or that supplemented with dl-Met or l-Met at 0.05, 0.10, 0.15, or 0.20% of feed. During the grower phase (15 to 35 d), ducks were fed a basal diet (Met, 0.24%) or that supplemented with dl-Met or l-Met at 0.04, 0.08, 0.12, or 0.16% of feed. Compared with ducks fed the basal diet, supplementation with either dl-Met or l-Met increased the body weight (BW) of ducks at days 14 and 35, increased average daily gain (ADG) and average daily feed intake (ADFI), decreased F:G at the starter phase, and increased ADG over the whole 35-d period (P < 0.05). The efficacy of l-Met compared to dl-Met was 140.1% for 14-d BW, 137.6% for ADG and 121.0% for F:G for days 1 to 14. Ducks fed diets supplemented with l-Met had greater proportion of leg muscle, higher than in ducks provided with dl-Met (P < 0.05). The breast muscle proportion was enhanced with dl-Met rather than l-Met supplementation (P < 0.01). The back feathers score and fourth primary wing feather length were increased with dl-Met or l-Met supplementation (P < 0.01), and there was increased efficacy of l-Met relative to dl-Met for back feathers score (153.1%). Dietary dl-Met or l-Met supplementation increased villus height of ileal mucosa of ducks at days 14 and 35 (P < 0.01). Overall, dietary l-Met or dl-Met supplementation affected the growth performance of ducks during the starter phase, and improved the feather traits and small intestinal morphology. The efficacy of l-Met to dl-Met ranged from 120 to 140% for growth performance of young ducks (1 to 14 d) and was 153% for the feather traits of ducks (35 d).

The effect of total sulfur amino acid levels on growth performance, egg quality, and bone metabolism in laying hens subjected to high environmental temperature.

This study evaluated the effects of total sulfur amino acid (TSAA) levels on performance, egg quality, and bone metabolism in laying hens subjected or not to high environmental temperature (HT). HyLine W36 layers (n = 144) were randomly distributed in a 2 × 3 factorial arrangement. Room temperature (control, CR: 21°C/24 h; and high temperature, HR: 32°C/8 h) and diets (70, 85, or 100% of TSAA) were the main factors, with 4 replicates of 6 birds (19 to 45 wk). The TSAA levels were obtained by adding L-Methionine (L-Met) to the basal diet (70% of TSAA) until 85 and 100% of TSAA were reached. At weeks 21, 34, and 45, growth performance, egg production, and egg quality traits were evaluated. At 45 wk, bones were evaluated for collagenous and non-collagenous proteins, bone volume, mineral content, and mineral density from total, cortical, trabecular, and medullary portions. When interactions were found, the increase of TSAA levels (85 and 100%) was able to counteract the negative effects of HT. In general, HT reduced egg production (P < 0.05) and did not significantly affect bone quality. The birds fed 70% of TSAA showed higher feed conversion, lower body weight, egg weight, and egg mass than birds fed 85 and 100% of TSAA in at least one phase. The birds fed 100% of TSAA showed higher egg production and egg mass than the other treatments at 21 wk of age. The cortical and trabecular bone mineral densities were higher for birds fed 100 than 70% of TSAA, whereas the medullary bone mineral content and density were higher for birds fed 70 than 100% of TSAA. In conclusion, HT had negative impact on performance, egg quality and no effect on bone development. The supplementation of L-Met until either 85 or 100% of TSAA levels were reached was enough to assure good performance, egg quality, and bone development in laying hens subjected or not to HT.

[The correlation between normal or abnormal vestibule function and prognosis of the low frequency sudden deafness].

Objective:To study the correlation between prognosis and status of the vestibule functions with the patients of the low frequency sudden deafness (SD). Method:Eighty-eight patients with low frequency SD were enrolled in this study, the cervical vestibular evoked myogenic potential (cVEMP), the ocular VEMP (oVEMP) and caloric test were evaluated. Based upon the results of the test, patients were divided into 4 groups. A group has no abnormal test results, B group has one abnormal test results, C group has two abnormal test results,and D group has three abnormal test results. Calculating and comparing the effective rate and uneffective rate were conducted in every group after treatment. Result:In A group, the effective rate is 27.27%, the uneffective rate is 2.27%. In B group, the effective rate is 36.36%, the uneffective rate is 4.55%.In C group, the effective rate is 9.09%, the uneffective rate is 6.82%. In D group, the effective rate is 0%, the uneffective rate is 13.64%. The difference between effective and uneffective rate was significant in group A, B, and D, while, there was no significant difference in group C. Conclusion:The prognosis of low frenquency SD patients without abnormal test results or only with one abnormal test results is good. While, the prognosis of patients with three abnormal test is bad. The prognosis of patients with two abnormal test is not sure. The vestibule functions test can be used to determine the prognosis of low frequency SD in clinical treatment.

DCE and DSC MR perfusion imaging in the differentiation of recurrent tumour from treatment-related changes in patients with glioma.

AIM: To retrospectively compare the utility of perfusion magnetic resonance imaging (MRI) in distinguishing treatment-related changes from recurrent disease in glioma patients. MATERIALS AND METHODS: Thirty-one patients with histologically diagnosed gliomas and increased enhancement after or during concurrent (chemo-) radiation therapy were enrolled. They underwent dynamic contrast-enhanced (DCE) permeability MRI followed by dynamic susceptibility contrast (DSC) perfusion MRI. The vascular transfer constant (rK(trans)) and initial areas under the concentration curve (riAUC) were obtained from DCE MRI, and cerebral blood volume (rCBV) was obtained from DSC MRI. Patients were classified as having treatment-related changes or recurrent tumours based on clinicoradiological results or pathological results from surgery. RESULTS: Nineteen patients were diagnosed as having recurrences and 12 patients as having treatment-related changes. The rK(trans), riAUC, and rCBV values in the recurrent group were significantly higher than the values in the group with treatment-related changes (p < 0.05). For all 31 patients, there was no significant difference between DSC MRI and DCE MRI for the differentiating power between recurrence and treatment-related changes (p = 0.7227). However, when including only the 24 patients with concordant values of rK(trans) and riAUC, DCE MRI showed a significant AUC value of 0.786 in the receiver operating characteristic (ROC) curve analysis (p = 0.003), whereas DSC MRI did not (AUC = 0.643, p = 0.229). CONCLUSION: MRI perfusion images appear to show promise in distinguishing treatment-related changes from recurrent tumours. When both rK(trans) and riAUC show concordant values, DCE MRI seems to be more powerful than DSC MRI in the differentiation of recurrence from treatment-related changes.

Selective depression of nociceptive responses of dorsal horn neurones by SNC 80 in a perfused hindquarter preparation of adult mouse.

Detailed electrophysiological characterisation of spinal opioid receptors in the mouse has been limited due to various technical difficulties. In this study, extracellular single unit recordings were made from dorsal horn neurones in a perfused spinal cord with attached trunk-hindquarter to investigate the role of delta-opioid receptor in mediating nociceptive and non-nociceptive transmission in mouse. Noxious electrical shock, pinch and heat stimuli evoked a mean response of 20.8+/-2.5 (n=10, P<0.005), 30.1+/-5.4 (n=58, P<0.005) and 40.9+/-6.3 (n=29, P<0.005) spikes per stimulus respectively. In 5 of 22 cells, repetitive noxious electrical stimuli applied to the hindpaw for 20 s produced a progressive increase in spike number, the phenomenon known as 'wind-up' and/or hyperactivity. When the selective delta-opioid receptor agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80) was perfused for 8-10 min, these evoked nociceptive responses were reversibly depressed. SNC 80 (2 microM) depressed the nociceptive responses evoked by electrical shock, pinch and heat by 74.0+/-13.7% (n=8, P<0.01), 66.5+/-16.6% (n=10, P<0.01) and 74.1+/-17.0% (n=10, P<0.01) respectively. The maximum depression by 5 microM SNC 80 was 92.6+/-6.8% (n=3). SNC 80 at 5 microM also completely abolished the wind-up and/or hypersensitivity (n=5). The depressant effects of SNC 80 on the nociceptive responses were completely blocked by 10 microM naloxone (n=5) and 3 microM 17-(cyclopropylmethyl)-6,7-dehydro-4,5 alpha-epoxy-14 beta-ethoxy-5 beta-methylindolo [2',3':6',7'] morphinan-3-ol hydrochloride (HS 378, n=8), a novel highly selective delta-opioid receptor antagonist. Interestingly, HS 378 (3 microM) itself potentiated the background activity and evoked responses to pinch and heat by 151.8+/-38.4% (P<0.05, n=8), 34.2+/-6.1% (P<0.01, n=7) and 45.5+/-11.8% (P<0.05, n=5) respectively. In contrast, the responses of non-nociceptive dorsal horn neurones were not inhibited by SNC 80 at a dose of up to 10 microM (n=5). These data demonstrate that delta-opioid receptor modulate nociceptive, but not non-nociceptive, transmission in spinal dorsal horn neurones of the adult mouse. The potentiation of neuronal activity by HS 378 may reflect an autoregulatory role of the endogenous delta-opioid in nociceptive transmission in mouse.

Pulmonary intravascular lymphomatosis: presentation with dyspnea and air trapping.

Intravascular lymphomatosis (IVL) is a rare lymphoid neoplasm that is typically of B-cell lineage and characterized by proliferation of malignant cells within small arterioles, capillaries, and venules. We report a patient with pulmonary IVL who presented clinically with progressive dyspnea, fever, and a dry cough. Pulmonary function tests revealed a marked decrease in diffusion capacity with airflow obstruction and severe air trapping. High-resolution CT (HRCT) of the chest with inspiratory and expiratory images revealed mosaic attenuation consistent with air trapping. Transbronchial biopsies revealed the diagnosis of IVL with capillary expansion in the alveolar and peribronchiolar interstitial tissue. IVL should be considered in the differential diagnosis of a patient with an interstitial lung disease, air trapping on pulmonary function tests, and mosaic attenuation on HRCT. Transbronchial biopsies may be the initial diagnostic procedure of choice.

The inverted nipple: its grading and surgical correction.

Inverted nipples have been treated by various methods by many authors, but the relationship between the grade of the deformity and the appropriate surgical procedure is not clearly described. One hundred seven inverted nipples in 60 patients were treated from 1993 to 1997. They were divided into three groups by the authors' system of grading. The grade was made by preoperative evaluation of severity of inversion and was confirmed by the surgical findings. In grade I, the nipple is easily pulled out manually and maintains its projection quite well. Grade I nipples are believed to have minimal fibrosis; thus, manual traction and a single, buried purse-string suture are enough for the correction. The majority of inverted nipples belong to grade II, i.e., the nipples can be pulled out but cannot maintain projection and tend to go back again. These nipples are thought to have moderate fibrosis beneath the nipple. Blunt dissections for surgical release were carried out until the inversion did not recur after releasing the traction. The lactiferous ducts could be identified and preserved, permitting proper release of fibrotic bands in the grade II group. The purse-string suture was used. In grade III, to which the least number of inverted-nipple cases belong, the nipple can hardly be pulled out manually. Severe fibrosis made it impossible to reach optimal release of the fibrotic band with the preservation of the ducts. The fibrotic bands are widely dissected, and the lactiferous ducts are cut, especially in the central portion. Two or three deepithelialized dermal flaps may be used to make up for soft-tissue deficiency; a purse-string suture is also used. This grading system will be useful for patient classification and analysis, systematic planning, and application of the proper surgical procedures.

Is melatonin associated with the development of autoimmune hepatitis?

Melatonin is a neurohormone produced by the human pineal gland that plays a role in the regulation of many physiologic processes and has been proposed as a therapy for everything from insomnia to metastatic carcinoma. Melatonin is available in the United States without prescription, and adverse effects appear to be uncommon. However, because melatonin appears to have immunomodulatory properties, the potential exists for the development of autoimmune-related side effects. We describe a patient in whom characteristic clinical and laboratory features of autoimmune hepatitis developed after beginning melatonin therapy for the treatment of insomnia. Liver biopsy demonstrated histologic features of autoimmune hepatitis. Rapid symptomatic and biochemical improvement resulted from the initiation of immunosuppressive therapy; however, hepatitis recurred after the withdrawal of steroid therapy. The temporal relation observed between melatonin use and the development of autoimmune hepatitis raises the possibility that the drug might be involved in the pathogenesis of this patient's autoimmune disease.

Nucleotide sequences from tomato leaf curl viruses from different countries: evidence for three geographically separate branches in evolution of the coat protein of whitefly-transmitted geminiviruses.

The coat protein (CP) gene-containing circular DNA molecule of an isolate of tomato leaf curl geminivirus (ITmLCV; 2749 nt) obtained from southern India, and the CP genes of tomato yellow leaf curl geminivirus isolates from Nigeria and two regions of Saudia Arabia were sequenced. ITmLCV DNA had the same arrangement of ORFs, and the same pattern of repeats in the large intergenic region as is found in in DNA-A of other whitefly-transmitted geminivirus (WTGs) from the Old World. However, the sequence of ITmLCV DNA and the sequences of its predicted translation products differed substantially from those of other WTGs, including one isolate obtained from a tomato plant in northern India. Comparison of the four CP sequences deduced here with those of 18 WTGs previously studied indicated that their relationships can be represented by a tree with three branches that are unrelated to plant host species but which contains viruses from the Americas, Africa to the Middle East, and Asia to Australia, respectively. It is suggested that WTG CP evolution has proceeded along different paths in these three main regions, and that WTGs have adapted freely to new hosts in each region. Indeed, the virus isolates causing similar diseases of tomato plants in the different continents are, with few exceptions, not closely related and warrant recognition as separate species.

Nucleotide sequence evidence for the occurrence of three distinct whitefly-transmitted geminiviruses in cassava.

The complete nucleotide sequence of the DNA of Indian cassava mosaic virus (ICMV) and a key part of that of a group B isolate of African cassava mosaic virus from Malawi (ACMV-M) were determined and compared at the nucleotide and encoded amino acid levels with the published sequences of an ACMV group A isolate (ACMV-K) and other whitefly-transmitted gemini-viruses (WTGs). The DNA of ICMV consists of two circular single-stranded molecules, DNA-A [2815 nucleotides (nt)] and DNA-B (2645 nt), which differ substantially in sequence from the genome components of ACMV-K (DNA-A 70%, DNA-B 47% sequence identity) and other WTGs. ICMV DNA-A contains eight open reading frames (ORFs) encoding proteins of > 100 amino acid residues, of which four ORFs (one genome sense, three complementary sense) are comparable to those of other WTGs. DNA-B contains one ORF in each sense, as in other WTGs. None of the putative viral proteins are more similar in amino acid sequence to the proteins of ACMV-K than to those of another WTG. The coat protein of ACMV-M is more like that of tomato yellow leaf curl virus from Sardinia (86% sequence identity) than those of ICMV or ACMV-K. The intergenic regions of ACMV-K, ACMV-M and ICMV DNAs differ in size, and largely in sequence, except for two 30 to 40 nt sequences which are also conserved in other WTGs and can form stem-loop structures. The intergenic region of ICMV DNA contains three copies of a 41 nt sequence, and that of ACMV-M DNA contains an imperfect repeat of a 34 nt sequence which resembles the repeated sequence in ICMV DNA. The differences between ACMV-K, ACMV-M and ICMV are considered great enough to justify their separation as isolates of three distinct WTGs: African cassava mosaic virus, East African cassava mosaic virus and Indian cassava mosaic virus.

Glutamate, NMDA and NMDA receptor antagonists: cardiovascular effects of intrathecal administration in the rat.

Selected excitatory amino acids and antagonists were tested for their effects on arterial pressure and heart rate when administered intrathecally at the second (T2) or ninth (T9) thoracic spinal levels in urethane-anesthetized Sprague-Dawley rats with spontaneous or artificial respiration. Intrathecal administration of glutamate (1 mumol) and N-methyl-D-aspartic acid (NMDA; 2 nmol) at T9 increased arterial pressure and heart rate. The response began within 1 min, peaked at 2-3 min and persisted for 8-15 min. The maximum changes were 20-25 mm Hg for arterial pressure and 40-50 beats/min for heart rate. These responses were prevented by systemic administration of hexamethonium (10 mg/kg). Responses to administration of NMDA at the two spinal levels were essentially the same. Effects elicited by NMDA but not by glutamate were blocked by pretreatment with the NMDA receptor antagonists, D,L-2-amino-5-phosphonovaleric acid (APV; 10 nmol, intrathecal administration) and ketamine (7 mg/kg, i.v.). Intrathecal administration of APV (10, 50 and 200 nmol) at T2 produced dose-dependent decreases in arterial pressure without changing heart rate. The results support the hypothesis that NMDA receptors are involved in regulation of sympathetic output at the spinal level. They also indicate that in this preparation there is a tonic activation of NMDA receptors in sympathetic pathways to the vessels but not to the heart. Finally, the persistence of the response to glutamate in the presence of NMDA receptor antagonists suggests the involvement of non-NMDA receptors in spinal control of sympathetic output.

Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat.

In a previous study it was found that i.t. administration of L-baclofen decreased arterial pressure and heart rate while D-baclofen differentially increased arterial pressure. The objective of the present study was to determine which of these effects was blocked by prior administration of the GABAB receptor antagonist, phaclofen, and whether the effect of one enantiomer of baclofen could be blocked by prior administration of the other. The decreases in systolic and diastolic arterial pressures and in heart rate produced by i.t. administration of 70 nmol of L-baclofen were unaffected by i.t. administration of 7, 70 or 700 nmol of D-baclofen 10 min prior to administration of L-baclofen, but were blocked by administration of 5 mumol of phaclofen given 3-5 min prior to L-baclofen. On the other hand, the increases in systolic and diastolic arterial pressures induced by i.t. administration of 700 nmol of D-baclofen were blocked by 70 nmol but not by 7 nmol of L-baclofen, as well as by 2.5 mumol of phaclofen; the effect of L-baclofen cannot be attributed to a desensitization of D-baclofen-sensitive receptors as two successive doses of D-baclofen given 7 min apart had quantitatively similar effects. Phaclofen alone increased systolic and diastolic arterial pressures and heart rate. The results are interpreted as indicating that D-baclofen is not an antagonist of L-baclofen in this paradigm; rather, they suggest that L-baclofen reduces the effects of D-baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular responses to intrathecal administration of strychnine in the rat.

Experiments were done to determine the influence of spinal glycinergic mechanisms in regulating sympathetic output to the heart and vessels in the anaesthetized male Sprague-Dawley rat. Intrathecal administration of 65 (n = 6) and 130 (n = 8) nmol of strychnine, but not of a lower dose (32.5 nmol, n = 8), to the second thoracic segment increased heart rate within one minute (P less than 0.01). Similar administration of artificial cerebrospinal fluid (n = 16) had no effect. The increase in heart rate in response to strychnine peaked at 5-7 min (+35.1 +/- 5.8 bpm with 130 nmol), and slowly returned toward baseline values over the next 25 min. Arterial pressure was unaffected by this treatment. These effects were not mimicked by administration of strychnine (n = 6) at the third lumbar spinal level or by intravenous infusion of strychnine (n = 4) and were abolished by systemic injection of hexamethonium (n = 6). The results suggest that there is a tonic glycine-mediated inhibition of sympathetic output at the spinal level.