Effects of Whistling Compared with Buzzy Device During Blood Sampling on Pain and Fear in Children's Emergency Department.

Blood sampling from a peripheral vein in children can be significant. Pediatric nurses should be able to use the techniques which decrease the pain and fear duration of the blood sampling. This research studied the effect of vibration bee and whistling (concentrate on breathing) blood sampling on pain and fear in the children's emergency. In this randomized clinical trial study, 120 children ages 3-6 years referred to a pediatric ward in Najaf, Iraq, using Random Blocking Method, were divided into three groups; vibration bee, whistling, and control group. A musical vibration bee, with the cold bag attached to it, was closed for 5 minutes at approximately 5-10 cm above the blood sampling site. A final minute, the vibration was applied; then, the procedure was done. The pain severity was measured by Wong Baker Faces scale. Data were analyzed by SPSS19 software at the significant level of 95%. There was a significant difference in pain intensity between the control groups and the intervention groups (p = .000). Moreover, there was a significant difference in children's medical fear scale between the control groups and the intervention groups (p = .000). Whistling (concentrate on breathing) may be an easily accessed, inexpensive, and effective technique to control or reduce pain and fear in young children. But, vibration bee with cold has a greater effect for reducing pain and fear. It is suggested to use vibration bee (with cold) in painful aggressive procedures in children.

Electromyographical Assessments of Recommended Neck and Trunk Positions for Dental Hygienists.

Purpose: Dental professionals are recommended to limit neck and trunk flexion to within 20° of a neutral (0°) body posture, however empirical support for the recommendations is lacking. The purpose of this study was to determine whether there are differences in muscle workload between a range of neck and trunk postures in a population of dental hygiene students.Methods: Fifteen first semester senior dental hygiene students with no history of neck and trunk injury volunteered to participate. Surface electromyography was used to record muscle activity from two neck extensors muscles, cervical erector spinae (CES) and upper trapezius (UT), and two trunk extensor muscles, thoracic erector spinae (TES) and iliocostalis lumboruni (IL). Participants performed ten conditions, including five neck flexion angles (0°, 10°, 20°, 30°, 40°) and five trunk flexion angles (0°,10°, 20°, 30°, 40°). For each trial, posture was checked with a goniometer and maintained for 20s. Muscle activity for each muscle was normalized to the individual's maximum voluntary isometric contraction (MVIC).Results: Activity of the CES was significantly lower in the neutral position than all flexed neck positions. Activation of the UT increased with neck flexion but required 30° of flexion to differ significantly from the neutral position. Activity of the TES required 20° of trunk flexion to differ significantly from neutral and IL activity in the neutral position was significantly lower than all other trunk flexion conditions.Conclusion: Even small amounts of neck or trunk flexion (10°), within the recommended range (≤ 20°), can significantly increase the workload for some muscles in an oral health care provider.

Impact of IL28 Genotypes and Modeling the Interactions of HCV Core Protein on Treatment of Hepatitis C.

BACKGROUND: Mutations in the core CVR region of hepatitis C virus (HCV) and polymorphisms of interleukin 28B (IL28B) are associated with progression toward liver disease and in response to therapy. In addition, interactions of the core protein with some cell interactors can be related to HCV liver damage. AIM: This study aimed to evaluate the effect of core mutations as well as IL28B polymorphism on clinical features, sustained virological response (SVR) in 1a and 3a HCV genotypes amongst Iranian HCV infected patients, and the impact of mutations on core protein properties, antigenic properties, and interactions with HCV inhibitors, using several bioinformatics tools. METHODS: Seventy-nine Iranian patients infected with HCV genotypes 1a and 3a and diagnosed with chronic active hepatitis were examined. Plasma viral RNA was used to amplify and sequence the HCV Core gene; also, HCV viral load, molecular genotyping, and the liver enzymes were determined for all samples. The sequencing results were analyzed by several reliable bioinformatics tools to determine the physicochemical properties, B cell epitopes, post-modification changes, and secondary/tertiary structures; and evaluate the interactions with 4 drugs by docking method. RESULT: There were some substitutions in core CVR related to ALT and AST enzymes that can lead to HCV advanced liver disease. The most prevalent mutation for 3a genotypes was a substitution in aa 162 (I to V) while we did not find any mutation in 1a responder group. Polymorphism of the rs8099917 showed that the majority of patients had TG heterozygous and carried CT genotype at the rs12979860. Analysis indicated several phosphorylation sits for core protein as well as two important disulfide bonds. Immunogenic prediction showed that core protein can strongly induce the immune system. Interaction analysis, using the docking method revealed two potential interactors (Vitronectin and SETD2). CONCLUSION: Generally, mutations in all core CVR regions in all patients showed a relationship between such substitutions and higher liver enzymes that can result in advanced liver disease progression in HCV infected patients. Furthermore, immunoinformatics analysis determined the possible immunodominant regions to be considered in HCV vaccine designs. Furthermore, no association between SVR and IL28B polymorphism was shown. In silico analysis determined modification sites, structures, B-cell epitopes of core protein and interactions with several interactors can lead to persistent HCV infection in the cell and the progress of liver diseases.

Protective Role of Angiotensin Type 1 Receptor Blockade in 4/6 Nephrectomized Male and Female Rats.

BACKGROUND: Chronic kidney disease associated with serious morbidity and mortality rate while it is affected by renin-angiotensin system. The effects of losartan as angiotensin II Type 1 receptor antagonist on renal functional in 4/6 nephrectomized rats was evaluated. METHODS: Twenty-six male and female Wistar rats underwent 4/6 nephrectomy, and the animals from each gender were randomly divided into two groups which treated with vehicle and losartan (10 mg/kg/day for 1 week). The parameters related to kidney function were measured. RESULTS: Creatinine (Cr) clearance and urine flow were improved in losartan-treated group significantly (P < 0.05). The serum level of blood urea nitrogen and Cr and kidney tissue damage score and sodium urinary output (UNaV) did not alter. However, losartan decreased percentage of sodium excretion (ENa%) in both genders insignificantly. CONCLUSIONS: Losartan may improve renal function in 4/6 nephrectomized male rats.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

High rate of A2142G point mutation associated with clarithromycin resistance among Iranian Helicobacter pylori clinical isolates.

This study aimed to investigate the clarithromycin resistance and its associated molecular mechanisms among Helicobacter pylori isolates from dyspeptic patients in Shiraz, Iran. From January to May 2014, 100 H. pylori strains were isolated from patients with gastroduodenal disorders. The resistance to clarithromycin was quantitatively evaluated, using Epsilometer (E-test) method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on all the isolates to detect A2143G and A2142G mutations in 23S rRNA gene. The H. pylori isolation rate was found to be 31.4%. E-test showed that 20% of isolates were resistant to clarithromycin (MIC ≥ 1 mg/L). MIC of clarithromycin ranged between 0.016 and 24 mg/L. Findings of PCR-RFLP showed that the A2142G was the most (90%) frequently point mutation, followed by the A2143G (10%). No statistically significant difference was found between H. pylori clarithromycin resistance point mutations and patients' gender or age. To the best of our knowledge, this is the first report of high frequency of A2142G point mutation in Iran and probably in other regions of the world. Considering the increasing trend of H. pylori resistance to clarithromycin due to these mutations, it is crucial to investigate the new therapeutic approaches against H. pylori infection.

Susceptibility to Ulcerative Colitis and Genetic Polymorphisms of A251G SOD1 and C-262T CAT.

BACKGROUND: Reactive oxygen species can attack and damage almost every molecule found in living cells, including proteins, carbohydrates, lipids, and DNA. For this reason, their production is normally tightly controlled. Among the most important defenses against these radicals are the superoxide dismutase (SOD) enzymes and catalase (CAT). Increasing attention has been given to the role of reactive oxygen metabolites in the pathogenesis of ulcerative colitis (UC), which is defined as an idiopathic and chronic intestinal inflammation. Accordingly, we hypothesized a relation between genetic polymorphisms in the two antioxidant enzymes SOD1 A251G (rs2070424) and CAT C-262T (rs1001179) and the risk of UC. METHODS: The present case-control study included 109 UC patients (46 males and 50 females) and 186 (67 males and 119 females) gender-matched healthy controls. Genotyping was done by the PCR-RFLP method. RESULTS: After adjusting for age and gender, a significant association was observed between the AG+GG genotypes of SOD1 A251G polymorphism (vs. AA genotype) and risk of UC (OR=0.29, 95% CI: 0.10-0.86, P= 0.025) after adjusting for age and gender. Our statistical analysis revealed that the CAT C-262T polymorphism did not associate with the risk of UC before and/or after adjusting for age and gender. CONCLUSIONS: Based on the present statistical analysis, the G allele of the SOD1 A251G polymorphism decreases the risk of UC, thus it might be assumed that the G allele has a protective role.

Role of nitric oxide in kidney and liver (as distance organ) function in bilateral renal ischemia-reperfusion: Effect of L-Arginine and NG-nitro-L-Arginine methyl ester.

BACKGROUND: Renal ischemia-reperfusion (RIR) is a major cause of renal dysfunction that acts through different mechanisms. We investigated the role of L-Arginine as an endogenous nitric oxide (NO) precursor and NG-nitro-L-Arginine methyl ester (L-NAME) as an NO inhibitor on kidney and liver function in RIR model. MATERIALS AND METHODS: Fifty-eight Wistar rats were randomly assigned to four groups. Groups 1 (sham-operated, n = 13) received a single dose of saline (4 ml/kg, i.p.) and 2 (Ischemia [Isch], n = 14) received a single dose of saline (4 ml/kg, i.p.). Groups 3 (Isch + L-NAME, n = 15) received a single dose of L-NAME (20 mg/kg, i.p.) and 4 (Isch + L-Arginine n = 16) received a single dose of L-Arginine (300 mg/kg, i.p.), After 2 h, renal failure was induced by clamping both renal pedicles for 45 min, followed by 24-h reperfusion in Groups 2-4. Finally, blood samples were obtained, and kidney tissue samples were subjected for pathology investigations. RESULTS: The body weight decreased, and the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), and kidney tissue damage score (KTDS) increased significantly in the Isch and Isch + L-NAME groups compared with the sham group while L-Arginine improved weight reduction (P < 0.05), and it reduced the serum levels of BUN and Cr, and KTDS when compared with the Isch and Isch + L-NAME groups. Kidney weight increased significantly in all groups compared with the sham group. L-Arginine reduced the liver tissue level of malondialdehyde and increased alkaline phosphatase. CONCLUSION: L-Arginine as an NO precursor can improve kidney function against RIR. It also improves oxidative stress in liver tissue.

Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats.

BACKGROUND: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B. OBJECTIVES: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephrotoxicity in ovariectomized-estradiol (Es) treated rats. MATERIALS AND METHODS: Thirty-six ovariectomized Wistar rats were divided into 6 groups. Group 1 received CP (2.5 mg/kg/day) for one week. Groups 2 and 3 received 2 different doses of Es (0.25 and 0.5 mg/kg/week) for 3 weeks, but CP was started in the third week. Group 4 was treated as group 1, but bosentan (BOS, 30 mg/kg/day) was also added. Groups 5 and 6 treated similar to groups 2 and 3 but CP and BOS were added in the third week. At the end of the experiment, blood samples were obtained, and the animals were sacrificed for histopathological investigation of kidney tissue. RESULTS: The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) increased by CP; however, BOS significantly elevated the BUN and Cr levels that were increased by CP administration (P < 0.05). Co-treatment of Es, BOS, and CP decreased the serum levels of BUN, Cr, and malondialdehyde (MDA) when compared with the group treated with BOS plus CP (P < 0.05). Such finding was obtained for kidney tissue damage score (KTDS). As expected, Es significantly increased uterus weight (P < 0.05). The groups were not significantly different in terms of serum and kidney nitrite, kidney weight (KW), and bodyweight Conclusions: According to our findings, BOS could not protect renal functions against CP-induced nephrotoxicity. In contrast, Es alone or accompanied with BOS could protect the kidney against CP-induced nephrotoxicity via reduction of BUN, Cr, and KTDS.

Role of endothelin-1 antagonist; bosentan, against cisplatin-induced nephrotoxicity in male and female rats.

BACKGROUND: Cisplatin (CP) is a chemotherapy drug, with the major side effect of nephrotoxicity. The level of endothelin-1 (ET-1) increases during nephrotoxicity, which is accompanied with vasoconstrictive properties. Bosentan (BOS) is a nonselective ET-1 receptor antagonist, having vasodilatory and anti-hypertension effects. The purpose of this study was to investigate the renoprotective effect of BOS against CP-induced nephrotoxicity in male and female rats. MATERIALS AND METHODS: Male and female rats were divided into six groups; groups 1-3 and 4-6 were male and female rats, respectively. Animals in groups 1 and 4 were considered as negative control and groups 2 and 5 considered as positive control groups received BOS (30 mg/kg/day) alone and CP (2.5 mg/kg/day) alone, respectively, for 1-week. The animals in groups 3 and 6 were treated with both CP and BOS. Finally, serum parameters were measured, and the kidney tissue was subjected to staining to evaluate tissue damage. RESULTS: The serum levels of blood urea nitrogen and creatinine, kidney tissue damage score and kidney weight elevated, and body weight significantly decreased in both CP alone and in CP plus BOS-treated groups when compared with the control groups (P < 0.05), while BOS did not ameliorate these parameters neither in males nor in females. No significant differences were observed in serum levels of nitrite and malondialdehyde between the groups, but kidney tissue level of nitrite decreased significantly in CP alone and CP plus BOS-treated groups (P < 0.05). CONCLUSION: Renoprotective effect of BOS, as ET-1 blocker, was not observed against CP-induced nephrotoxicity neither in male nor in female rats. This is while BOS promoted the severity of injuries in females.

Willingness to pay for the social health insurance in Iran.

OBJECTIVE: The substantial level of out-of-pocket expenditure for health care by the population causes policy makers to draw particular attention to the proposal of a social health insurance for uninsured members of the community. Hence, it is essential to gather reliable information about the amount of Willingness To Pay (WTP) for health insurance. We assessed the WTP for health insurance in Iran in order to suggest an affordable social health insurance. METHODS: The study sample included 300 household heads in all Iranian provinces. The double bounded dichotomous choice approach was used to elicit the WTP. RESULTS: The average WTP for social health insurance per person per month was 137 000 Rial (5.5 $US). Household heads with higher levels of education, income and those who worked had more WTP for the health insurance. Besides, the WTP increased in direct proportion to the number of insured members of each household and in inverse proportion to the family size. CONCLUSIONS: From a policy point of view, the WTP value can be used as a premium in a society. An important finding of this study is that although households' Willingness To Pay is not more than the total insurance premium, households are willing to pay more than the premium they ought to pay for health insurance coverage. That is, total insurance premium is 150 000 Rials and households ought to pay approximately half of this sum. This can afford policy makers the ideal opportunity to provide good insurance coverage for medical services according to the need of society.

Angiotensin Type-1 Receptor Blockade May Not Protect Kidney against Cisplatin-Induced Nephrotoxicity in Rats.

Background. Cisplatin (CDDP) is an anticancer drug, which is accompanied with major side effects including nephrotoxicity. We tested two doses of losartan (10 and 20 mg/kg/day) against nephrotoxicity in a rat model treated with daily administration of CDDP (2.5 mg/kg/day). Methods. Five groups of rats were examined. Groups 1 and 2 received losartan 10 and 20 mg/kg/day, i.p, for a period of 10 days. Group 3 received saline for 10 days, but from day 3 the animals received CDDP (2.5 mg/kg/day, i.p) for the next seven days. Groups 4 and 5 received treatment regimen the same as groups 1 and 2, but from day 3 they also received CDDP for the next seven days. At the end of the experiment, blood samples were obtained and the kidneys were removed to undergo pathological investigation and to obtain supernatant from homogenized tissue. Results. CDDP induced nephrotoxicity, but the serum levels of creatinine and blood urea nitrogen were not attenuated by losartan. The pathological findings confirmed that losartan did not have nephroprotective effect in this experimental model. Conclusion. According to the findings, losartan could not improve renal function impaired by toxicity induced by continuous doses of CDDP, and also it worsened the renal failure.

Pomegranate Flower Extract does not Prevent Cisplatin-Induced Nephrotoxicity in Female Rats.

BACKGROUND: Nephrotoxicity is the major side-effect of cisplatin (CDDP), and it is reported to be gender-related. We evaluated the effects of pomegranate flower extract (PFE) as an antioxidant on CDDP-induced nephrotoxicity in female rats. METHODS: Twenty-three adult female rats in four groups treated as following. Groups 1 and 2 received PFE at doses of 25 and 50 (mg/kg/day), respectively, for 9 days, and from day 3 on, they also received cisplatin (CDDP) (2.5 mg/kg) daily. Group 3 was treated as group 1 expects saline instead of PFE, and group 4 received PFE (25 mg/kg/day) alone. RESULTS: Cisplatin alone increased the serum levels of blood urea nitrogen, creatinine, and nitrite; and kidney tissue damage score and kidney weight. However, PFE not only did not ameliorate the induced nephrotoxicity, but also aggravated renal tissue damage. CONCLUSIONS: Pomegranate extract as an antioxidant did not ameliorate CDDP-induced nephrotoxicity in female rats.

N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat.

BACKGROUND: One of the most common causes of acute kidney injury (AKI) is kidney ischemia/reperfusion injury (IRI). The distant organ injury such as acute lung injury is one of the side effects of AKI or kidney IRI. In this study, we performed bilateral renal IRI in rats and the protective role of N-acetylcysteine (NAC) in kidney and lung was investigated. METHODS: Rats (n = 30) were randomly assigned to four experiment groups. The group 1 was assigned as sham-operated group. Before kidney IRI performance, the others groups were treated with saline (group 2), 150 mg/kg (group 3) or 500 mg/kg (group 4) of NAC, and the treatment were continued daily after IRI for next 3 days. At day 3, the all groups' animals were subjected for the measurements. RESULTS: The serum level of blood urea nitrogen (BUN) and creatinine (Cr) in the control group increased significantly (P < 0.05), and administration of NAC (150 mg/kg) decreased the serum levels of Cr and BUN. However, only the serum level of Cr decreased significantly (P < 0.05). NAC did not improve kidney weight and damage; however, its low dose (150 mg/kg) attenuated the lung injury score (P < 0.05) when compared with the control group. No significant differences were observed in lung water content and endothelial permeability, serum levels of malondialdehyde and nitrite between the groups. CONCLUSIONS: Low dose of NAC as a protectant agent may protect the kidney function and lung tissue damage after kidney IRI.

Contributory role of viral infection in congenital tumour development.

Congenital tumours are a group of distinct infrequent disorders whose exact aetiologies have not clearly been understood so far. Viral infection seems to be one of the key factors involved in the carcinogenesis of certain tumours. This study was performed to assess whether viral DNAs are present in the congenital tumours or not. Nucleic acid from 31 congenital tumours was extracted. Detection of Epstein-Barr virus, Cytomegalovirus (CMV), adenovirus, Herpes simplex virus 1 (HSV1) and 2, Human herpes virus 6 (HHV6), and BK virus was performed using polymerase chain reaction. Viral nucleic acid was detected in eight subjects (25.8%), mostly adenovirus, CMV, and HHV6. Despite their low frequencies, a possible role could be identified for viral infections in tumour development or progression.

Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats.

Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, n = 6 and group 2, female, n = 6) received saline. Groups 3 (male, n = 8) and 4 (female, n = 8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male, n = 8) and 6 (female, n = 8) received CP (3 mg/kg) for 7 days. Groups 7 (male, n = 8) and 8 (female, n = 8) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats (P < 0.05). CP alone increased kidney damage significantly (P < 0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.

Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model.

BACKGROUND: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. METHODS: Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. RESULTS: The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05). CONCLUSIONS: EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.

Serotonin transporter gene polymorphisms in Southwestern Iranian patients with irritable bowel syndrome.

BACKGROUND AND STUDY AIMS: Irritable bowel syndrome is a common chronic functional gastrointestinal disorder of unknown etiology. Serotonin is an important factor in sensory signaling in the brain-gut axis, which plays a key role in intestinal motility and secretion. Serotonin clearance is mediated by a specific protein called the serotonin reuptake transporter. Transcription activity of the serotonin transporter gene is affected by some polymorphisms in this gene. The aim of this study was to investigate the relationship between serotonin transporter gene polymorphisms and irritable bowel syndrome. PATIENTS/MATERIAL AND METHODS: The 5-HTTLPR, rs25531 and STin2VNTR polymorphisms of the serotonin transporter gene were analyzed by PCR-based methods in 50 patients with irritable bowel syndrome and 100 healthy controls. RESULTS: Serotonin transporter polymorphisms were similar in patients and healthy controls. There were no significant differences in allele or genotype frequencies between the two groups. CONCLUSION: Our findings suggest that polymorphisms in the gene encoding for the serotonin transporter are not associated with irritable bowel syndrome. Interactions between environmental factors and predisposing genetic factors are important in the pathophysiology of irritable bowel syndrome, and further genetic and epigenetic research may provide novel insights into the mechanisms contributing to this disease.

Colchicine is effective for short-term treatment of slow transit constipation: a double-blind placebo-controlled clinical trial.

PURPOSE: Although colchicine has been tested in clinical trials for treatment of constipation, the index groups in those trials were composed of special patient groups with developmental neuromuscular defects or failed surgical management. The aim of this study is to investigate the efficacy of colchicine in patients with refractory slow transit constipation. MATERIALS AND METHODS: Sixty patients with chief complaint of chronic constipation due to slow transit consented to be included in the double-blind placebo-controlled clinical trial. These patients were randomly divided into two groups (each containing 30 patients) to receive either colchicine, 1 mg QD, (group A) or placebo (group B) for 2 months. At the end of the study, Knowles-Eccersly-Scot symptom (KESS, a valid technique to assist in the diagnosis and evaluation of symptoms in constipation) scores were compared between the case and control groups. RESULTS: The mean KESS score measured at the end of 2 months was 11.67 +/- 3.91 for colchicine and 18.66 +/- 3.72 for placebo group (p = 0.0001). CONCLUSION: This trial shows that low-dose colchicine is effective in treatment of slow transit constipation.

In vitro comparison of the vitamin D endocrine system in 1,25(OH)2D3-responsive and -resistant melanoma cells.

We studied effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], its analog seocalcitol (EB 1089), and 25-hydroxyvitamin D3 [25(OH)D3], on the growth of seven melanoma cell lines. While three cell lines (MeWo, SK-Mel-28, SM) responded to antiproliferative effects of active vitamin D analogs, the others (SK-Mel-5, SK-Mel-25, IGR, MeUuso) were resistant. A strong induction (7000-fold) of 1,25-dihydroxyvitamin D-24-hydroxylase (24OHase, CYP24) mRNA was detected in responsive cell lines along with 1,25(OH)2D3-treatment, indicating functional integrity of vitamin D receptor (VDR)-mediated transcription. In contrast, induction of 24OHase was much lower in resistant melanoma cells (70-fold). VDR mRNA was induced up to 3-fold both in responsive and resistant cell lines along with 1,25(OH)2D3-treatment. RNA for vitamin D-activating enzymes vitamin D-25-hydroxylase (25OHase, CYP27A1) and 25-hydroxyvitamin D-lalpha-hydroxylase (lalphaOHase, CYP27B1) was detected in all melanoma cell lines analyzed, additionally we show splicing variants of lalphaOHase in SK-Mel-28 cells. Expression of 250Hase and laOHase was marginally modulated along with treatment. Proliferation of melanoma cells was not inhibited by treatment with 25(OH)D3, indicating no significant stimulation of endogeneous production of antiproliferative acting 1,25(OH)2D3. In conclusion, we characterize the vitamin D endocrine system in melanoma cells and demonstrate that the majority of melanoma cell lines analyzed is resistant to antiproliferative effects of 1,25(OH)2D3. It can be speculated that these alterations are of importance for pathogenesis and growth of metastasizing malignant melanoma. Additionally, our findings indicate that only a minority of cases with metastasizing melanoma may represent a promising target for palliative treatment with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of 1,25(OH)2D3-synthesis/metabolism.