Histamine regulates pancreatic carcinoma cell growth through H3 and H4 receptors

Inflammation Research -     

Negative modulation of nitric oxide production by neurotensin as a putative mechanism of the diuretic action of SR 48692 in rats

1. We investigated the effect of the non-peptide neurotensin (NT) antagonist SR 48692 on renal function in rats and the involvement of nitric oxide (NO) in the diuretic action of this compound.
2. In fed animals, SR 48692 dose-dependently (0.5 to 12.5 mg kg⁻¹, p.o., 0.03 to 1 mg kg⁻¹, i.p. and 0.1 to 1 μg/rat, i.c.v.) increased urine output and urinary excretion of Na⁺, K⁺ and Cl⁻ and reduced urine osmolality. The diuretic activity was also evident in water-deprived, fasted animals and in fasted, water-loaded rats.
3. NT (0.1 μg/rat, i.c.v.) had no effect on urine output in fed rats, but reduced the diuretic action of SR 48692 (1 μg/rat, i.c.v.). The opposite result was obtained in fasted, water-loaded animals: NT dose-dependently (0.01 and 0.1 μg/rat, i.c.v.) inhibited diuresis and this effect was significantly inhibited by i.c.v. SR 48692. In this experimental condition, SR 48692 did not further increase the on-going diuresis.
4. The NO synthesis inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME; 30 mg kg⁻¹, i.p.) alone had no effect on urine output in fed rats but prevented the diuretic action of i.c.v. or i.p. SR 48692; L-arginine (1 g kg⁻¹, i.p.) but not D-arginine (1 g kg⁻¹, i.p.) restored the SR 48692-dependent increase in diuresis. L-NAME had no effect on furosemide-stimulated diuresis.
5. Systemically administered L-NAME or i.c.v. NT in fasted, water-loaded rats significantly reduced water diuresis but this effect was no longer seen in animals given i.p. L-arginine. Rats receiving i.c.v. NT, whose diuresis was significantly reduced, also excreted less nitrates and nitrites in urine.
6. Increased diuresis after central or systemic administration of SR 48692 to fed rats was paralleled by increased urinary excretion of nitrates and nitrites, this being consistent with peripheral enhancement of NO production after NT-receptor blockade by SR 48692. The increase in diuresis after furosemide also involved an increase of nitrates and nitrites in urine, but this effect was about half that attained with an equipotent diuretic dose of SR 48692.
7. In fed rats, the NO donor isosorbide-dinitrate, reduced systolic blood pressure (unlike SR 48692 which did not affect blood pressure) but also dose-dependently (1 and 5 mg kg⁻¹, i.p.) stimulated urine output.
8. The overall effects of SR 48692 strongly support a link between the actions of endogenous NT, AVP and peripheral NO production in the modulation of renal excretion of water, Na⁺, K⁺ and Cl⁻.

     

Manometric patterns of rat colonic motor activity and defecation

We investigated in conscious and unrestrained rats, the major patterns of colonic pressure waves, as related to defecation. A manometric low compliance perfusion system, which was set at a very low flow rate (0.03 ml/min), permitted simultaneous recordings of intraluminal pressure in the proximal, transverse, and distal colon. Pressure waves in control rats reflected two types of motor activity: short-duration waves (<15 sec), that were frequent throughout the colon (about 40–90/hr with aborally decreasing frequency), and propulsive, long-duration, high-amplitude waves (>15 sec, >15 mm Hg) that occurred only occasionally (1/hr or less) in the transverse and distal, but not in the proximal colon; these waves appeared to migrate aborally and were associated with defection. The serotonin 5HT_1A agonist 8-OH-DPAT dramatically and dose-dependently increased the frequency of long-duration, high-amplitude waves in the transverse and distal colon, and concurrently promoted defecation; these effects were prevented by the putative 5HT_1A antagonist pindolol. We conclude that 5HT_1A agonists such as 8-OH-DPAT may promote defecation and occurrence of propulsive waves through the same serotoninergic mechanism.A preliminary account of this work was presented at the 13th International Symposium on Gastrointestinal Motility, Kobe, Japan, Abstract 172. J Gastrointest Motil 3, 1991.     

Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon

BACKGROUND & AIMS: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut. METHODS: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro. RESULTS: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528. CONCLUSIONS: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.     

Targeting galectin‐1‐induced angiogenesis mitigates the severity of endometriosis

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvic pain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of the disease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutic targets, we investigated the involvement of galectin‐1 (Gal‐1), an endogenous glycan‐binding protein endowed with both immunosuppressive and pro‐angiogenic activities, in the pathophysiology of endometriotic lesions. Here we show that Gal‐1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Using an experimental endometriosis model induced in wild‐type and Gal‐1‐deficient (Lgals1^?/?) mice, we showed that this lectin orchestrates the formation of vascular networks in endometriotic lesions in vivo, facilitating their ectopic growth independently of vascular endothelial growth factor (VEGF) and the keratinocyte‐derived CXC‐motif (CXC‐KC) chemokine. Targeting Gal‐1 using a specific neutralizing mAb reduced the size and vascularized area of endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal‐1 during endometriosis and validate this lectin as a possible target for the treatment of disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Clinical and epidemiological characteristics of septic arthritis of the hip, 2006 to 2012, a seven-year review

OBJECTIVE:

To epidemiologically characterize the population treated at our orthopedic clinic with a diagnosis of septic arthritic of the hip between 2006 and 2012.

METHODS:

Fifteen patients diagnosed with septic arthritis of the hip between 2006 and 2012 were retrospectively evaluated. The patients'' clinical and epidemiological characteristics were surveyed; a sensitivity profile relating to the microorganisms that caused the infections and the complications relating to the patients'' treatment and evolution were identified.

RESULTS:

Septic arthritis was more common among males. Most diagnoses were made through positive synovial fluid cultures, after joint drainage was performed using the Smith-Petersen route. Among the comorbidities found, the most prevalent were systemic arterial hypertension, diabetes mellitus, and human immunodeficiency virus. The pathological joint conditions diagnosed prior to joint infection were osteoarthrosis and developmental dysplasia of the hip. The infectious agent most frequently isolated was Staphylococcus aureus. From the clinical and laboratory data investigated, 53.33% of the cases presented with fever, and all except one patient presented with increased measures in inflammation tests. Gram staining was positive in only 26.66% of the synovial fluid samples analyzed. Six patients presented with joint complications after treatment was administered.

CONCLUSION:

S. aureus is the most common pathogen in acute infections of the hip in our setting. Factors such as clinical comorbidities are associated with septic arthritis of the hip. Because of the relatively small number of patients, given that this is a condition of low prevalence, there was no statistically significant correlation in relation to worse prognosis for the disease.