The effect of central administration of alpha-pinene on capsaicin-induced dental pulp nociception.

AIM: To assess the effects of central administration of α-pinene alone and in combination with either bicuculline or naloxone, as GABAA and µ-opioid receptor antagonists, respectively, on capsaicin-induced dental pulp stimulation in rats. METHODOLOGY: Forty-eight adult male Wistar rats aged 2 months (230-270 g) were cannulated via their lateral ventricles for the central administration of the drugs. α-Pinene was injected at 0.1, 0.2 and 0.4 µmol L-1 . Then, dental pulp stimulation was induced by intradental application of capsaicin solution (100 µg), and nociceptive scores were recorded for up to 40 min. For investigation of the anti-inflammatory effects of α-pinene, expression of COX-2 in the subnucleolus caudalis (Vc) of rats was determined using immunofluorescence staining. Nonparametric repeated measure Friedman and Kruskal-Wallis tests as well as parametric one-way analysis of variance were used for the statistical analysis. RESULTS: α-Pinene at 0.2 and 0.4 µmol L-1 was able to decrease capsaicin-induced nociception. Moreover, there was a significant increase in the expression of COX-2-positive cells in the Vc of capsaicin-treated rats (P < 0.01). This effect was prohibited by α-pinene (0.4 µmol L-1 ). Co-administration of bicuculline (1 µg per rat) or naloxone (6 µg per rat) with α-pinene (0.4 µmol L-1 ), however, prevented the inhibitory effects of α-pinene on both capsaicin-induced pulp nociception and COX-2 over-expression. CONCLUSIONS: Pinene exhibited significant curable effects on capsaicin-induced pulpal nociception and inflammation mainly via pharmacological interfacing with GABAA and µ-opioid receptors.

Activation of orexin-1 receptors in the ventrolateral periaqueductal grey matter (vlPAG) modulates pulpal nociception and the induction of substance P in vlPAG and trigeminal nucleus caudalis.

AIM: To characterize the role of orexin-1 receptors (OX1Rs) in ventrolateral periaqueductal grey matter (vlPAG) on modulation of capsaicin-induced pulpal nociception in rats. METHODOLOGY: Sixty-six adult male Wistar rats (2 months old) weighing between 230 and 260 g were used. The animals were cannulated for microinjection of drugs into the vlPAG matter. Pulpalgia was induced by intradental application of capsaicin solution (100 µg) into the incisor teeth of the rats. Ten min prior to capsaicin application, orexin-A (50, 100 and 150 pmol L-1 per rat) was administered. Orexin-A (150 pmol L-1 ) was also co-administrated with SB-334867 (40 nmol L-1 per rat), an OX1Rs antagonist; or bicuculline (1 µg per rat), a GABAA receptors antagonist. Moreover, treatment effects on the release of pro-nociceptive modulator substance P (SP) in vlPAG and trigeminal nucleus caudalis (Vc) of rats were explored using an immunofluorescence technique. One-way analysis of variance was used for the statistical analysis. RESULTS: Orexin-A dose-dependently decreased capsaicin-induced nociceptive behaviour. However, SB-334867 (40 nmol L-1 per rat) pretreatment (P < 0.05), but not bicuculline (1 µg per rat), attenuated the analgesic effect of orexin-A (150 pmol L-1 ). The level of SP was significantly increased in Vc and decreased in vlPAG of capsaicin-treated rats (P < 0.05). Capsaicin-induced changes in SP levels, however, were prohibited by orexin-A treatment (150 pmol L-1 ) (P < 0.05). CONCLUSIONS: Orexin-A administration into the vlPAG was associated with an inhibitory effect on capsaicin-induced pulpal nociception and bidirectional effects on the induction of SP in vlPAG and Vc of rats. Central activation of OX1Rs is a potential therapeutic tool for pulpalgia.

Orexin-1 receptors in the rostral ventromedial medulla are involved in the modulation of capsaicin evoked pulpal nociception and impairment of learning and memory.

AIM: To investigate the role of rostral ventromedial medulla orexin-1 receptors in the modulation of orofacial nociception as well as nociception-induced learning and memory impairment in adult male rats. METHODOLOGY: Pulpal nociception was induced by intradental application of capsaicin (100 µg) into the incisors of rats. Orexin-1 receptors agonist (orexin-A, 10, 25 and 50 pmol L-1  rat-1 ) and antagonist (SB-334867-A, 40 and 80 nmol L-1  rat-1 ) were microinjected into the rostral ventromedial medulla prior to capsaicin administration. Total time spent on nocifensive behaviour was recorded by direct visualization of freely moving rats whilst learning and memory were evaluated by the Morris water maze test. One-way analysis of variance and repeated-measures were used for the statistical analysis. RESULTS: Capsaicin-treated rats had a significant increase of nocifensive behaviours (P < 0.001), as well as learning and memory impairment (P < 0.001). However, intraventromedial medulla prior micro-injection of orexin-A (50 pmol L-1  rat-1 ) significantly reduced the nociceptive behaviour (P < 0.001). This effect was blocked by pre-treatment with SB334867-A (80 nmol L-1  rat-1 ). Orexin-A (50 pmol L-1  rat-1 ) also inhibited nociception-induced learning and memory deficits. Moreover, administration of SB-334867-A (80 nmol L-1  rat-1 ) plus orexin-A (50 pmol L-1  rat-1 ) had no effect on learning and memory deficits induced by capsaicin. CONCLUSIONS: The data suggest that rostral ventromedial medulla orexin-A receptors are involved in pulpal nociceptive modulation and improvement of learning and memory deficits induced by intradental application of capsaicin.

Propensity score-matched comparison of oncological outcomes between laparoscopic and open distal pancreatic resection.

BACKGROUND: Selected studies have reported improved outcomes in laparoscopic compared with open distal pancreatic resection. Concerns regarding failure to achieve proper oncological resection and compromised long-term outcomes remain. This study investigated whether postoperative outcomes and long-term survival after laparoscopic distal pancreatectomy are comparable to those after an open procedure. METHODS: This retrospective case-control study included patients who underwent distal pancreatectomy for resectable pancreatic adenocarcinoma between 2010 and 2013, identified from the National Cancer Database. Propensity score nearest-neighbour 1 : 1 matching was performed between patients undergoing laparoscopic or open distal pancreatectomy based on all relevant co-variables. The primary outcome was overall survival. RESULTS: Of 1947 eligible patients, 605 (31·1 per cent) underwent laparoscopic distal pancreatectomy. After propensity score matching, two well balanced groups of 563 patients each were analysed. There was no difference in overall survival at 3 years after laparoscopic versus open distal pancreatectomy (41·6 versus 36·0 per cent; hazard ratio 0·93, 95 per cent c.i. 0·77 to 1·12; P = 0·457). The overall conversion rate was 27·3 per cent (165 of 605). Patients who underwent laparoscopic distal pancreatectomy had outcomes comparable to those of patients who had an open procedure with regard to median time to chemotherapy (50 versus 50 days; P = 0·342), median number of nodes examined (12 versus 12; P = 0·759); 30-day mortality (1·2 versus 0·9 per cent; P = 0·562); 90-day mortality (2·8 versus 3·7 per cent; P = 0·403), 30-day readmission rate (9·6 versus 9·2 per cent; P = 0·838) and positive margin rate (14·9 versus 18·5 per cent; P = 0·110). However, median duration of hospital stay was shorter in the laparoscopic group (6 versus 7 days; P < 0·001). CONCLUSION: Laparoscopic distal pancreatectomy is an acceptable alternative to open distal pancreatectomy with no detriment to survival.

Prognostic significance of lymph node yield in ypN0 rectal cancer.

BACKGROUND: Neoadjuvant radiation therapy for locally advanced rectal adenocarcinoma decreases lymph node yield. This study investigated the association between survival and number of lymph nodes evaluated in patients with pathologically negative nodes after neoadjuvant therapy. METHODS: Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and had pathologically negative lymph nodes were included from the Surveillance, Epidemiology, and End Results (SEER) database over a 7-year interval (January 2004 to December 2010). Systematic dichotomization for optimal cut-off point identification was performed using statistical modelling. RESULTS: A total of 3995 patients met the inclusion criteria. The majority had T3 (66·7 per cent) and moderately differentiated (71·5 per cent) tumours. The median number of lymph nodes retrieved was 12 (i.q.r. 7-16). An optimal cut-off of nine lymph nodes was identified. Increasing age (P < 0·001), increasing T category (T4 versus T1, P < 0·001; T3 versus T1, P = 0·010), response to neoadjuvant therapy (P < 0·001) and number of nodes evaluated (P < 0·001) were significant factors for overall survival in univariable analysis. After adjustment in the multivariable model, the group with nine or more nodes examined had significantly better overall survival (hazard ratio (HR) 0·76, 95 per cent c.i. 0·65 to 0·88, P < 0·001; 5-year survival 83·2 versus 78·0 per cent) and cancer-specific survival (HR 0·76, 0·64 to 0·92, P = 0·004; 5-year survival 87·9 versus 85·1 per cent) than the group with one to eight nodes examined. CONCLUSION: Overall and cancer-specific survival were worse where fewer than nine lymph nodes were identified after neoadjuvant therapy for locally advanced rectal cancer.

Comparative study of subcutaneous tissue responses to a novel root-end filling material and white and grey mineral trioxide aggregate.

AIM: To compare the subcutaneous tissue response to grey mineral trioxide aggregate (GMTA), white mineral trioxide aggregate (WMTA) and a new experimental cement (calcium enriched cement, CEM). METHODOLOGY: Thirty-six Wistar male albino rats each received three implants, containing one of the tested materials, and an empty tube as a control. Seven, 30 and 60 days after implantation, the animals were sacrificed. After histological preparation and H&E staining, the specimens were evaluated for capsule thickness, necrosis, and for the type, the severity, and the extent of inflammation. Kruskal Wallis and Chi-square tests were used for data analysis. RESULTS: After 1 week, CEM produced no necrosis compared to both types of WMTA and GMTA (P = 0.007). After 30 days, GMTA specimens had significantly less inflammation compared with WMTA and CEM (P = 0.011). After 60 days, less inflammation was associated with CEM specimens (P = 0.0001) compared to the other materials. Dystrophic calcifications in the connective tissue adjacent to all experimental material were detected. CONCLUSION: Histological observation illustrated that all materials were well tolerated by the subcutaneous tissues.

Effects of different respiratory maneuvers on esophageal sphincters in obese patients before and during anesthesia.

BACKGROUND: Data on esophageal sphincters in obese individuals during anesthesia are sparse. The aim of the present study was to evaluate the effects of different respiratory maneuvers on the pressures in the esophagus and esophageal sphincters before and during anesthesia in obese patients. METHODS: Seventeen patients, aged 28-68 years, with a BMI ≥ 35 kg/m², who were undergoing a laparoscopic gastric by-pass surgery, were studied, and pressures from the hypopharynx to the stomach were recorded using high-resolution solid-state manometry. Before anesthesia, recordings were performed during normal spontaneous breathing, Valsalva and forced inspiration. The effects of anesthesia induction with remifentanil and propofol were evaluated, and positive end-expiratory pressure (PEEP) 10 cmH2O was applied during anesthesia. RESULTS: During spontaneous breathing, the lower esophageal sphincter (LES) pressure was significantly lower during end-expiration compared with end-inspiration (28.5 ± 7.7 vs. 35.4 ± 10.8 mmHg, P<0.01), but barrier pressure (BrP) and intra-gastric pressure (IGP) were unchanged. LES, BrP (P<0.05) and IGP (P<0.01) decreased significantly during anesthesia. BrP remained positive in all patients. IGP increased during Valsalva (P<0.01) but was unaffected by PEEP. Esophageal pressures were positive during both spontaneous breathing and mechanical ventilation. Esophageal pressures increased during PEEP from 9.4 ± 3.8 to 11.3 ± 3.3 mmHg (P<0.01). CONCLUSION: During spontaneous breathing, the LES pressure was the lowest during end-expiration but there were no differences in BrP and IGP. LES, BrP and IGP decreased during anesthesia but BrP remained positive in all patients. During the application of PEEP, esophageal pressures increased and this may have a protective effect against regurgitation.

First Report of Tobacco streak virus Infecting Safflower (Carthamus tinctorius) in Maharashtra, India.

Safflower, Carthamus tinctorius L. (Asteraceae), is extensively cultivated in India, China, and other parts of Asia for edible oil, dyeing agent, and its medicinal value. In 2003, safflower entry (NARI-6) in the All-India Coordinated Research Project on Oilseeds (Safflower) grown in the experimental fields of M/s Syngenta India Ltd., Aurangabad (Maharashtra State, India) exhibited symptoms of veinal and leaf necrosis, necrotic streaks on the stem, necrosis of the terminal bud, and ultimately plant death. The disease was attributed to Tobacco streak virus (TSV) because sunflower growing adjacent to safflower showed similar symptoms caused by TSV (1). Mechanical inoculations of sap from symptomatic safflower leaves caused typical symptoms of TSV (local, irregular, necrotic rings, veinal necrosis, and systemic veinal necrosis) on Vigna unguiculata (L.) Walp. cv. C-152 and Phaseolus vulgaris (L.) cv. Topcrop, and symptoms of local, necrotic lesions, veinal necrosis, and systemic necrosis of leaf and growing bud on Arachis hypogaea L. cv. JL-24. Sap-inoculated safflower cv. Manjeera showed chlorotic and necrotic local lesions followed by systemic leaf necrosis, leading to necrosis and death of the terminal bud. Safflower cvs. A-1, BIP-2, Co-1, and Bheema (10 plants of each cultivar) inoculated with sap from safflower plants showing typical TSV symptoms did not show any visible symptoms except stunting, but six to nine plants of each cultivar tested positive for TSV using enzyme-linked immunosorbent assay (ELISA) tests. In direct antigen coating-ELISA, the virus reacted positively with antiserum produced to an isolate of TSV from peanut (2) and to antiserum to TSV (ATCC-PVAS 276 for Datura stramonium), but did not react to peanut bud necrosis tospovirus antiserum. Examination of leaf extracts using leaf-dips and immunosorbent electron microscopy with the antiserum of TSV-peanut isolate showed isometric particles resembling those in the genus Ilarvirus. To our knowledge, this is the first report of an isolate of Tobacco streak virus infecting safflower. References: (1) R. D. V. J. Prasada Rao et al. J. Oilseeds Res. 17:400, 2000. (2) A. S. Reddy et al. Plant Dis. 86:173, 2002.