Molecular Phylogenetic Analysis of Iranian HDV Complete Genome

Hepatitis D (delta) virus (HDV) is a subviral pathogen agent and a satellite of Hepatitis B virus. Three distinct genotypes are described for HDV; genotype I is distributed worldwide but other genotypes appear to be more restricted geographically. In the present study, the entire nucleotide sequence of an HDV isolate from an Iranian patient (IR-1) was obtained using twelve pairs of primers to amplify six overlapping fragments covering the whole HDV genome by RT-nested PCR. Phylogenetic and pairwise alignments were done on this new isolate to determine IR-1 position among other isolates. Our results indicate that IR-1 contains 1676 nucleotides encoding 214 a.a. of the hepatitis delta antigen (HDAg). This new isolate belongs to genotype I with most sequence similarity to an Italian HDV isolate (92.6%). At amino acid level, predicted HDAg sequence of IR-1 revealed the most homology with those of Italian and Lebanese isolates. Data analysis confirmed genetic variability and heterogeneity of the HDV species isolated from different geographical areas.     

Analgesic effect of paracetamol combined with low-dose morphine versus morphine alone on patients with biliary colic: a double blind,randomized controlled trial

BACKGROUND: Numerous drugs have been proposed to alleviate pain in patients with biliary colic, especially opioids, but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients. The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic.METHODS: A randomized double-blind controlled trial was performed in 98 patients with biliary colic, recruited from two emergency departments from August 2012 to August 2013. Eleven patients were excluded and the remaining were randomized into two groups: group A received 0.05 mg/kg morphine+1 000 mg paracetamol in 100 mL normal saline and group B received 0.1 mg/kg morphine+normal saline (100 mL) as placebo. Pain scores were recorded using visual analogue scale (VAS) at baseline and 15 and 30 minutes after drug administration. Adverse effects and the need for rescue medication (0.75 μg/kg intravenous fentanyl) were also reported within 60 minutes of drug administration.RESULTS: Before the infusion, the mean±SD VAS scores were 8.73±1.57 in group A and 8.53±1.99 in group B. At 15 minutes after drug administration, the mean±SD VAS scores were 2.16±1.90 in group A vs. 2.51±1.86 in group B; mean difference was -0.35, and 95%CI -1.15 to 0.45 (P=0.38). At 30 minutes the mean±SD VAS scores were 1.66±1.59 in group A vs. 2.14±1.79 in group B; mean difference was -0.48, and 95%CI -1.20 to 0.24 (P=0.19). The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference.CONCLUSION: Paracetamol combined with low-dose morphine may be effective for pain management in patients with biliary colic.     

The effect of the moisture content of a local heat source on the blood flow response of the skin

Numerous studies have examined the effect of local and global heating of the body on skin blood flow. However, the effect of the moisture content of the heat source on the skin blood flow response has not been examined. Thirty-three subjects, without diabetes or cardiovascular disease, between the ages of 22 and 32 were examined to determine the relationship between the effects of dry vs. moist heat applied for the same length of time and with the skin clamped at the same skin temperature on the blood flow response of the skin. The skin, heated with an infrared heat lamp (skin temperature monitored with a thermocouple) to 40°C for 15 min, was either kept moist with wet towels or, in a separate experiment, kept dry with Drierite (a desiccant) between the towels to remove any moisture. Before and after heat exposure of the forearm, blood pressure, heart rate, skin moisture content, skin temperature, and skin blood flow were recorded. The results of the experiment showed that there was no change in skin moisture after 15 min exposure to dry heat at 40°C. However, with moist heat, skin moisture increased by 43.7%, a significant increase (P < 0.05). With dry heat, blood flow increased from the resting value by 282.3% whereas with moist heat, blood flow increased by 386% over rest, a significant increase over dry heat (P < 0.05). Thus, with a set increase in skin temperature, moist heat was a better heating modality than dry heat. The reason may be linked to moisture sensitivity in calcium channels in the vascular endothelial cell.     

Prevalence of pulmonary thromboemboli among referred cadavers having hospitalization records to Tehran Legal Medicine Center

BACKGROUND: Pulmonary thromboemboli are one of the main causes of sudden death especially in hospitalized patients and appeared with different nonspecific manifestations. The aim of this study was to determine the prevalence of thromboemboli. MATERIALS AND METHODS: In this cross sectional study, pulmonary autopsies of 200 cadavers who were selected randomly from all cadavers with clinical suspicion of thromboemboli referred to Tehran University Tissue Archive in different months from January 2005 to 2006 and the prevalence of pulmonary embolism in these cases and its relation with demographic characteristics and sources of disease was assessed. Also, agreement degree of clinical and histopathological diagnosis of pulmonary embolism was calculated. RESULTS: The prevalence of pulmonary embolism was estimated at 13.5%. There were positive relationship between prevalence of pulmonary embolism and increased of age (P=0.001). Interpretation of results of macroscopic and histopathological studies for diagnosis of embolism showed moderate agreement (kappa=0.59) and interpretation of results of clinical diagnosis of disease before death and pathologic findings after death showed poor agreement (kappa=0.34). The most frequent detected location of emboli were end branches of pulmonary artery. CONCLUSION: Considering the apparent high prevalence of pulmonary embolism in our study, we recommend increased use of anti-deep vein thrombosis measures in all appropriate patients within the Tehran hospital population, according to evidence-based guidelines.     

SIRT1 and Klotho expression in the heart and kidneys of rats with acute and chronic renovascular hypertension

AimTo evaluate Klotho and SIRT1 expression in the heart and kidneys of rats with acute and chronic renovascular hypertension.MethodsFour and sixteen weeks after the induction of renovascular hypertension by clipping the left renal artery, systemic blood pressure, serum angiotensin II level, and the expression of Klotho and SIRT1 proteins and oxidative stress indices in the heart and kidneys were assessed.ResultsSIRT1 level was significantly reduced in the ischemic (left) kidney in acute and chronic phases of hypertension. In the heart, it decreased in the acute phase, but increased in the chronic phase. Klotho levels in the heart and kidneys did not change significantly in either hypertension phase. Superoxide dismutase (SOD) activity in the heart significantly decreased, and SOD, total antioxidant capacity, and malondialdehyde in the ischemic kidney significantly increased during the development of hypertension. Serum angiotensin II level significantly increased in the acute phase of hypertension.ConclusionDevelopment of renovascular hypertension was associated with a reduction of SIRT1 expression in the heart and ischemic kidney. As angiotensin II and SIRT1 counteract each other''s expression, a SIRT1 reduction in the heart and kidney, along with the influence of systemic/local angiotensin II, seems to be partly responsible for hypertension development. A combination of SIRT1 agonists and angiotensin II antagonists may be considered for use in the treatment of renovascular hypertension.

Hypertension is one of the leading causes of disease burden worldwide, doubling the risk of coronary artery diseases (1). The prevalence of hypertension in US adults in the 2013-2016 period ranged from 26.1% in the age group 20-44 to 78.2% among people older than 65 years (2). Despite antihypertensive treatment, blood pressure of more than half of American adults is not controlled (3). Thus, to be able to produce more effective drugs, the underlying mechanisms of hypertension should be investigated.The most common cause of death in hypertensive patients is hypertensive heart disease, which results from functional and structural adaptation of the heart to high blood pressure (1). Secondary hypertension is most frequently a result of primary kidney disease. On the other hand, hypertension is a risk factor for kidney damage and end-stage renal disease (1).Hypertension and related cardiovascular diseases are age-dependent (4,5). The aging of the cardiovascular system is an important process determining longevity (6).Sirtuins are a family of enzymes encoded by SIRT1 to SIRT7 in mammals that play important roles in longevity (7). These enzymes are abundantly expressed in the nucleus and cytoplasm of several tissues, including the heart and vascular endothelium (8). The most well-known member of the sirtuin family is SIRT1, which plays beneficial roles in age-associated metabolic, inflammatory, and cardiovascular diseases (9). SIRT1 has anti-oxidant, anti-inflammatory, and anti-apoptotic effects in the endothelium and prevents endothelial senescence and dysfunction (10,11). Several studies showed that SIRT1 protected against atherosclerosis (10-13). Increasing SIRT1 expression in mice improved vascular remodeling and hypertension caused by angiotensin II (14). In addition, through reducing SIRT1 expression, hyperglycemia causes vascular damage (15).Klotho is a membrane-bound protein that exerts anti-aging function (16). Klotho deficiency leads to premature aging phenotype and shortens the lifespan (17), while its increased gene expression increases life expectancy (18). Klotho is involved in the prevention of arteriosclerosis, inducing its effects even in tissues that do not express it, which indicates its endocrine role (16). A recent study on Klotho haplodeficient mice showed that Klotho deficiency led to arteriosclerosis and hypertension, but these effects were diminished by increasing SIRT1 activity (19).One of the experimental models to evaluate secondary hypertension is 2-kidney-1-clip (2K1C) hypertension (20). In this model, a clamp is placed on one of the renal arteries to induce ischemia, while the other renal artery remains intact. This procedure steadily increases blood pressure due to an increased activity of the renin-angiotensin system in the acute phase, and sodium and water retention in the chronic phase (20,21). As SIRT1 and Klotho play a role in blood pressure regulation, and the kidneys play a role in secondary hypertension, we hypothesized that these two proteins may partake in the development of acute and chronic renovascular hypertension. Therefore, the aim of this study was to assess the expression of these two proteins in the heart and in the ischemic and non-ischemic kidneys of 2K1C rats. On the other hand, it has been shown that angiotensin II infusion increases oxidative stress and blood pressure, and that the deleterious effects of angiotensin II on blood pressure and the kidneys can be prevented by an inhibition of reactive oxygen species after angiotensin II infusion (22) and in 2K1C rats (23). Furthermore, it has been shown that SIRT1 exerts its beneficial effects by reducing oxidative stress (11,24). Therefore, the amount of oxidative stress in the heart and kidneys of the experimental animals was also assessed.     

Right ventricular pressure elevated in one-kidney,one clip Goldblatt hypertensive rats

Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague–Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways.