Effect of peritonitis on gallbladder smooth muscle contractility in guinea pigs

BACKGROUND: The mechanisms involved in the impaired gallbladder contractile response in peritonitis are unknown. The aim of this study was to determine the effect of peritonitis on the contraction and relaxation responses to different agonists in gallbladder smooth muscle in guinea pig. MATERIALS AND METHODS: Peritonitis was induced by cecal ligation and puncture (CLP) in 10 guinea pigs. Another group of 10 guinea pigs underwent a sham operation and acted as controls. Twenty-four hours after the operation, the guinea pigs were killed, and gallbladder strips were placed in organ bath. The contraction responses to KCl, carbachol, and histamine, and relaxation responses to cyclooxygenase inhibitors (indomethacin, nimesulide, and DFU) on KCl-induced contractions were recorded. RESULTS: There was no significant difference between the contractile responsiveness to KCl, but maximum contractile responses (E(max)) to carbachol and histamine were significantly reduced. Indomethacin, nimesulide, and DFU concentration dependently inhibited on KCl-induced contractions of gallbladder smooth muscle. E(max) values of indomethacin, nimesulide, and DFU were significantly reduced in the peritonitis group compared with controls (P < 0.05). The inhibitor effects of nimesulide and DFU were considerably similar, but inhibitor effect of indomethacin was significantly less than that measured for nimesulide and DFU in both control and peritonitis groups (P < 0.05). CONCLUSIONS: The contraction responses to carbachol and histamine and relaxation responses to COX inhibitors on gallbladder smooth muscle are significantly decreased by peritonitis. Although the mechanism of the decrease in contraction and relaxation responses in CLP-induced peritonitis is completely unknown, we speculate that impaired smooth muscle responses may be related to an alteration in the regulation of receptor/postreceptor excitation-response coupling and/or through changes on Ca(2+) influx.     

Comparison of effects of cyclooxygenase inhibitors on myometrial contraction and constriction of ductus arteriosus in rats

The aim of this study was to compare the tocolytic effect of a selective cyclooxygenase-2 inhibitor, DFU (5,5-dimethyl-3(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), indomethacin and nimesulide on myometrial strips isolated from rats in both lipopolysaccharide-induced preterm labour and term labour. We also compared the constrictor effects of DFU and indomethacin on the fetal ductus arteriosus. Myometrial strips were obtained from preterm and term labour Wistar albino rats and were mounted in organ baths for the recording of isometric tension. DFU, nimesulide and indomethacin significantly inhibited KCl-, oxytocin-, prostaglandin E(2)- and prostaglandin F(2 alpha)-stimulated contractions of myometrial strips isolated from rats in preterm and term labour. The E(max) value of indomethacin was significantly lower than those for DFU and nimesulide (P<0.05), with no change-log (10) EC(50) values. There was no significant difference between in -log (10) EC(50) and E(max) values of DFU and nimesulide for any of the tissues (P>0.05). In addition, there was no significant difference between -log (10) EC(50) and E(max) values for each of these three agents in myometrial tissues isolated from rats in preterm and term labour (P>0.05). Fetal ductus arteriosus was significantly constricted by DFU (10 or 100 mg/kg) in preterm and term rats, although DFU (10 or 100 mg/kg)-induced constriction ratios were significantly lower than those for indomethacin (P<0.05). These data demonstrate that DFU, a specific cyclooxygenase-2 inhibitor, could be considered as a new therapeutic agent for preterm labour. However, careful attention should be given to constriction of the fetal ductus arteriosus.     

Levosimendan Improves Renal Function in Patients with Acute Decompensated Heart Failure: Comparison with Dobutamine

Background Levosimendan is a relatively new cardiac inotropic agent with calcium sensitizing activity. This study was conducted to investigate the effects of levosimendan (L) and dobutamine (D) on renal function in patients hospitalized with decompensated heart failure (HF). Method The present study included 88 consecutive patients hospitalized with acutely decompensated HF (New York Heart Association (NYHA) Class 3–4) requiring inotropic therapy. Patients were randomized 2:1 to either L or D for intravenous inotropic support. Diuretic therapy was kept constant during infusions. Renal function values, including serum creatinine (CR), blood urea nitrogen, 24-h urinary output levels and calculated glomerular filtration rate (GFR) were measured just prior to and 24 h after the infusions in all patients, and 48 and 72 h after the infusions in every second patient in both groups. The pre and post-infusion values of renal function and left ventricular ejection fraction (LVEF) were evaluated. Results LVEF increased significantly in both groups. Those in L showed a significant improvement in calculated GFR after 24 h, whereas those in D showed no significant change (median in change in L:+15.3%, median change in D: −1.33%). Furthermore, in the L group a significant improvement was observed in calculated GFR after 72 h compared to baseline levels, whereas in D no significant change (median change in L:+45.45%, median change in D: +0.09%) was seen. Both agents improved 24-h urinary output. Conclusion Levosimendan seems to provide beneficial effects in terms of improvement in renal function compared to dobutamine in patients with heart failure who require inotropic therapy.     

Alterations in spontaneous contractions of rat proximal and distal colon after peritonitis

Background/Purpose

The aim of this study was to investigate the effect of peritonitis on spontaneous contractions of distal and proximal colon smooth muscle isolated from rats.

Methods

Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, the rats were killed; and their distal and proximal colon smooth muscle was excised and placed in circular muscle direction in a 10-mL organ bath. Changes in the amplitude and frequency of contractions were analyzed before and after the addition of antagonists.

Results

Peritonitis induced the increase in the amplitude and frequency of spontaneous contractions. In both distal and proximal colon of the control group, the amplitude of spontaneous contractions was elevated by N^G-nitro-l-arginine and tetradotoxin; but the frequency of spontaneous contractions was significantly elevated only in the presence of N^G-nitro-l-arginine. In both distal and proximal colon of the peritonitis group, the enhanced amplitude and frequency were significantly decreased and returned to control values in the presence of celecoxib.

Conclusions

Peritonitis induces the increase in the amplitude and frequency of spontaneous contractions of distal and proximal colon, which can be attributed to a loss of inhibitor nitrergic and other neural control or rise of cyclooxygenase-2 levels.     

Imatinib Treatment Alone in Philadelphia-Positive Acute Lymphoblastic Leukemia: Is It Enough?

BCR-ABL fusion gene t(9;22)(q34;q11) occurs in only 3% of pediatric acute lymphoblastic leukemia (ALL) cases. Previously, less than 40% of Philadelphia-positive ALL patients were cured with intensive chemotherapy. The use of imatinib (340 mg/m(2)/day) added to an intensive chemotherapy regimen has improved the outcome in this population at 3 years to an event-free survival of 80%. Imatinib treatment alone was administered after remission induction chemotherapy to a patient with Philadelphia-positive ALL who presented with serious chemotherapy toxicity, so that intensive chemotherapy could not be maintained. This is the only patient in the literature who survived remission for more than 2.5 years with imatinib treatment only.     

Additive interaction of intraperitoneal dexmedetomidine and topical nimesulide, celecoxib, and DFU for antinociception

Nimesulide, celecoxib, and DFU (5, 5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone) are nonsteroidal anti-inflammatory drugs (NSAIDs) with selective cyclo-oxygenase (COX)-2 blocking properties and have potent analgesic and anti-inflammatory activities in oral and parenteral administrations. Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is an extremely potent antinociceptive agent. The present study was conducted to evaluate the antinociception induced by nimesulide, celecoxib, and DFU when topically applied on the tail in the absence or presence of intraperitoneal dexmedetomidine. Antinociception was measured in the radiant tail-flick test after immersion of the tail of rat into a solution of dimethyl sulfoxide (DMSO) containing nimesulide, celecoxib, or DFU. Antinociceptive effect of all drugs peaked at 60 min and decreased gradually to baseline levels at 240 min. Nimesulide had a potency lower than those of celecoxib, and DFU. The antinociceptive effect of dexmedetomidine was blocked by systemic pretreatment of selective alpha(2)-adrenoceptor antagonist, atipamezole. This suggests that antinociceptive effects of dexmedetomidine involve alpha(2)-adrenoceptors. Combination of topical COX-2 inhibitors with intraperitoneal dexmedetomidine yielded additive analgesic effect. These results demonstrate an additive interaction between topical COX-2 inhibitors with intraperitoneal dexmedetomidine. These observations are significant for physicians to combine selective COX-2 inhibitors and dexmedetomidine in the management of pain.     

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.     

Dermatological aspects of synthetic cannabinoid addiction

Context: Synthetic cannabinoids (SCs) have recently become one of the most abused substances among young population and have caused severe health consequences in our country and worldwide.

Objective: The aim of this study was to investigate sociodemographic and dermatological findings in SC addicts.

Materials and methods: A total of 136 SC users who applied to our hospital’s Substance Dependence Center outpatient clinic and diagnosed with drug addiction according to DSM-4 criteria between September 2014 and September 2015 were enrolled to our study. Patients were evaluated by dermatologist and psychiatrist with sociodemographic and clinical data sheets. Data were obtained by direct conversation with patients, clinical examination findings, and laboratory tests, if necessary.

Results: Of 136 patients, 12 (8.8%) were female and 124 (91.2%) were male, aged between 17 and 53 with mean age of 25.8?±?9.2. Most common use way of SC was smoking and patients majorly used opiates before SC. The majority of the patients enrolled to our study were low-educated and almost 50% did not have a regular job. The most frequent dermatologic complaints were periorbital darkening, hallowed-cheeks and premature aging, hair loss and gray hair, and acnes, whereas most frequent dermatologic examination findings were artifact lesions such as blade scars and tobacco scars-stains, tattoos, and acnes.

Discussion and conclusions: Given the increased prevalence of SC use in our country and around the world, dermatologists should continue to familiarize themselves with the common mucocutaneous markers of this substance use. Awareness of signs of SCs use will facilitate earlier diagnose, intervention, and directed treatment.