Mechanism of mast cell adhesion to human tenocytes in vitro

Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cell‐fibroblast co‐culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by α5β1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte‐conditioned media; the tenocyte‐derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on α5β1 integrin and tenocyte fibronectin. Additionally, tenocyte‐derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that α5β1 integrin mediates binding of mast cells to human tenocyte and to tenocyte‐derived ECM proteins, in particular fibronectin. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:9–16, 2015.

     

Pre‐medication and renal pre‐conditioning: a role for alprazolam,atropine, morphine and promethazine

Four pre‐medication drugs are used to relieve pain, allay anxiety, reduce secretion and enhance hypnosis, were evaluated for their effects on ischemia reperfusion (I/R) injury which is one of the major complications of vascular and transplantation surgery. Right kidney was removed from female rats (210–250 g) 3 weeks before surgical procedure. Different doses of morphine (0.5, 2 and 5 mg/kg), promethazine (1, 2 and 5 mg/kg), atropine (0.1, 0.3 and 0.5 mg/kg) and alprazolam (0.08, 0.32 and 0.64 mg/kg) were administered subcutaneously 30 min before left renal artery occlusion and 6 h reperfusion. Left kidneys were processed for histological evaluations. Creatinine and BUN were measured in serum samples. Morphine, promethazine, atropine and alprazolam at all evaluated doses significantly decreased serum creatinine and BUN levels and histopathological scores. The effects of promethazine (1 mg/kg) and all doses of alprazolam were more potent than other pre‐medication drugs and doses. This study suggested a protective effect of these pre‐medication drugs on I/R injury. Although obvious studies are required, these findings may lead to effective therapies against I/R injury.     

Calcium channel blocking activity of thioridazine,clomipramine and fluoxetine in isolated rat vas deferens: a relative potency measurement study

PURPOSE: We evaluated the calcium channel blocking activity of thioridazine, clomipramine and fluoxetine in isolated rat vas deferens and determined their relative order of potency. MATERIALS AND METHODS: Cumulative control concentration-response curves to calcium chloride were obtained in isolated rat vas deferens incubated in depolarizing calcium-free Krebs-Henseleit solution. Tissues were washed to baseline length and equilibrated with a given concentration of test drugs. After a 30-minute period a calcium concentration-response curve was repeated. The resulting rightward displacement of the concentration-response curve to calcium provided a dose ratio. The dose ratio was used in the Schild equation and the antagonism of calcium induced contractions was quantified by Schild analysis. RESULTS: The calcium channel blocking activity of thioridazine, clomipramine and fluoxetine was compared with nifedipine. All 4 drugs produced parallel rightward displacement of concentration-response curves to calcium. The potency of this effect was quantified by Schild analysis showing pA estimates, namely nifedipine 7, thioridazine 6.2, clomipramine 5.65 and fluoxetine 5. CONCLUSIONS: A characteristic profile of calcium channel blocking activity on the vas deferens was obtained for all test drugs. The relative order of potency was determined as thioridazine greater than clomipramine greater than fluoxetine. Differences in the potency of calcium entry blockade at peripheral end organs may contribute to differential effects of these drugs on delaying ejaculatory latency in patients with premature ejaculation.     

Canine Visceral Leishmaniasis in Boyer Ahmad District,Kohgiluyeh & Boyer Ahmad Province,Southwest of Iran

Background

Mediterranean type of visceral leishmaniasis (VL) is present in different parts of Iran. Several studies have identified dogs as the main reservoirs of the VL caused by Leishmania infantum in Iran and other Mediterranean regions. This study aimed to determine the seroprevalence of canine visceral leishmaniasis as animal reservoir host for human visceral leishmaniasis in Boyer Ahmad district in southwest of Iran.

Methods

A seroepidemiological study was carried out to determine the seroprevalence of canine visceral leishmaniasis (CVL) among ownership dogs by using direct agglutination test (DAT) in 23 of 182 villages of Boyer Ahmad district, during August 2009 to August 2010. One hundred and seventy serum samples from ownership dogs were selected by multi-stage cluster sampling in villages of Boyer Ahmad district. All samples were tested by DAT and anti-Leishmania antibodies titers at ≥ 1:320 was considered as positive.

Results

Of the 170 serum samples, 10% were positive by DAT at titers of 1:320 and higher. No statistical significant difference was found between male (10.7%) and female (8.3%) seroprevalence. The highest seroprevalence rate (15.1%) was observed among the ownership dogs of four to seven years age. Altogether, seventeen (25.4%) of the seropositive dogs had clinical signs and symptoms.

Conclusion

It seems that Boyer Ahmad district is an endemic area for canine visceral leishmaniasis in Iran.     

Abortifacient effect of Prangos ferulacia on pregnant rats

PURPOSE: Prangos ferulacea grows in southern Iran and used in Iranian herbal medicine for gastrointestinal disorders, but it seems it has an abortifacient effect on pregnant women. To verify its potential as an abortifacient agent, we administered the leaves of this plant to pregnant rats. MATERIAL AND METHODS: Hydroalcoholic and aqueous extract of the leaves was administered orally at different doses to 60 rats on the first 18 days of pregnancy. Group 1 (G1) was considered as control group and was given only water. Groups 2-5 (G2-G5) received 25, 50, 100 mg/g per day and Groups 6-8 (G6-G8) received 300, 500 and 1000 mg/g per day, respectively. On Day 18 of pregnancy, they were killed and laparotomized. The uterine horns of each group were opened to see whether they contained any live and degenerated/dead fetuses. We used Student's t-test to analyze the data (p < or = .05 was considered significant). RESULTS: Of the total 504 fetuses in the studied groups, 13 fetuses (2.57%) were aborted. The abortion rate in the control group was 2 (1.94%) of 103 fetuses; the abortion rate was higher in the treated groups but not statistically significant. There was no relationship between the dose and type of extract and abortion rate in all studied groups. CONCLUSION: This study shows that the aqueous or hydroalcoholic extract of P. ferulacea is ineffective on the rate of abortion of pregnant rats. Future studies should be performed with higher doses to test the efficacy of this agent on other animals.     

Association of inflammatory biomarkers with sleep disorders in hemodialysis patients

The aim of this study was to investigate the relationship between sleep disorders and C-reactive protein (CRP), hallmark of inflammation, and other biomarkers which may alter in hemodialysis patients. Our study included 108 patients who were dialyzed at least for 3?months. Before hemodialysis, blood samples were collected and serum levels of CRP, ferritin, albumin, phosphorus, parathyroid hormone, and hemoglobin were measured. Sleep disorders were confirmed by the presence of at least one of following criteria: insomnia, restless leg syndrome (RLS), obstructive sleep apnea syndrome (OSAS), narcolepsy, nightmare, sleepwalking, and poor sleep. 82.4% of patients demonstrated sleep disorders; insomnia (50%), RLS (32.4%), OSAS (7.4%), narcolepsy (15.7%), nightmare (15.7%), sleepwalking (0.9%), and poor sleep (71.3%). Our results revealed that CRP ≥3.8?μg/ml and advanced age were significantly associated with sleep disorders in these patients (p?=?0.004 and p?=?0.006, respectively). We concluded that inflammation has a close relation with sleep disorders in hemodialysis patients.