Volume 33, Issue 4

Arterial stiffness, defined as the rigidity of the arterial wall, is the consequence of vascular aging and is associated with the full spectrum of cardiovascular diseases. Carotid-femoral pulse wave velocity (cf-PWV) is the gold standard method for arterial stiffness evaluation: it measures the velocity of the arterial pulse along the thoracic and abdominal aorta alongside arterial distensibility. Its value rises as stiffness progresses. Cf-PWV is helpful to assess residual cardiovascular risk (CVR) in hypertension (HT). In fact, an increase in pulsatility and arterial stiffness predicts CVR in patients affected by arterial HT, independently of other risk factors. Arterial stiffness can predict cardiovascular events in several other clinical conditions such as heart failure, diabetes, and pulmonary HT. However, cf-PWV has not been yet included in routine clinical practice so far. A possible reason might be its methodological and theoretical limitations (inaccuracy in the traveled distance, intra and interindividual variability, lack of well-defined references values, and age- and blood pressure-independent cutoff). To exceed these limits a strict adherence to guidelines, use of analytical approaches, and possibility of integrating the results with other stiffness examinations are essential approaches.

One of the most frequent in-hospital electrolyte disturbances is hyponatremia. Hyponatremia in heart failure (HF) is mainly associated with hypervolemia resulting from activation of baroreceptor-mediated hormones, such as arginine vasopressin (AVP), renin–angiotensin–aldosterone system, and catecholamines. Various electrolyte imbalance can occur as heart failure progress. The goal of this review was to outline the current literature on hyponatremia in HF patients.

Objectives Several studies had been conducted to examine the link between diabetes and diabetes encephalopathy. This study was conducted to examine the potency of berberine (BER) on the restoration of impaired neurochemicals in the brain of streptozotocin (STZ)-induced diabetic Wistar rats. Methods Fifty-six (56) adult rats weighing between 200 and 230 g were randomly divided into seven groups (n=8) as follows; Group I is normal control; Groups II and III were normal rats treated with 50 and 100 mg/kg respectively; Group IV–VII were STZ-induced rats, but Groups V–VII were treated with acarbose (25 mg/kg), 50 and 100 mg/kg of BER, respectively. Results The result of the study showed that untreated STZ-induced diabetic rats have increased acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO) activities, and malonylaldehyde (MDA) level, with concomitant decrease of superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, and glutathione (GSH) level. However, daily treatment with 50 and 100 mg/kg BER and ACA significantly reversed these effects. Conclusions The findings of this study clearly indicated that BER possesses neuro-protective and antioxidative potentials and normalize neurochemical impairment distort by diabetes.

Objectives Paradoxical sleep deprivation has been associated with impaired salivary secretion in rats. However, the mechanism that underlies this is not known. Therefore, this study assessed salivary and serum oxidative stress levels following paradoxical sleep deprivation in rats. Methods Twenty-one male Wistar rats randomly divided into three groups of seven rats each as; Control (C); partial sleep-deprived (PSD); and total sleep-deprived (TSD) were used. Malondialdehyde (MDA) concentration, Superoxide dismutase (SOD), and catalase activities were evaluated in saliva, serum, and submandibular glands after seven days of sleep deprivation. Data were expressed as mean ± standard error of the mean and analyzed using one-way ANOVA, Tukey HSD post hoc, and Pearson’s correlation tests. Results Serum MDA levels were significantly higher in both the TSD and PSD groups compared to the control group whereas only the TSD group showed higher submandibular MDA levels compared to the PSD group and the control group. Submandibular SOD activity was significantly lower in both the TSD and PSD groups compared to the control group. Serum catalase activity was significantly lower in the TSD group only compared to the control group. Conclusions These results have demonstrated for the first time that paradoxical sleep deprivation was associated with changes in the oxidant/antioxidant defense system in the submandibular salivary glands of male Wistar rats which may contribute to impairment in salivary secretion.

Objectives Dietary high fat possibly causes oxidative stress; also it makes deleterious effect on kidney functions and land up in lipotoxicity in renal tissue. Lipotoxicity is the pathological situation where lipid Peroxidation occurs and generates reactive oxygen species (ROS). Overproduction of ROS than antioxidant present in tissues cause oxidative stress. Terminalia arjuna is found to be potential antioxidant that counteract oxidative stress and possibly maintain glomerular integrity. Methods Ethanolic extract of T. arjuna (ETO) was prepared and phytochemical analysis was done. Rats were divided into four groups, having six rats in each group as following; group 1-Control (20% fat); group 2 (ETO 100 mg/kg/b.wt); group 3 (30% fat) and group 4 (30% fat + ETO 100 mg/kg/b.wt). Dietary and ETO supplementation were continued for 21 days. Gravimetric, kidney functions (blood urea and serum creatinine) and oxidative stress markers like MDA, SOD and GSH were evaluated. Histopathological analysis was done on kidney along with measurement of glomerular integrity. Morphometrical analysis of glomerular integrity was evaluated by measuring glomerular length, width, glomerular area and Bowman’s capsule radius. One way ANOVA was done for analysis of data. Results Blood urea and serum creatinine levels were significantly higher in high fat fed rats indicating renal dysfunction. High fat diet showed significant increase in MDA, decrease in SOD and GSH in rats fed with high fat diet, which indicate generation of oxidative stress. Supplementation of ETO showed amelioratic effect against high fat diet induced renal dysfunction and oxidative stress. Histopathological findings were significantly corroborated with morphometrical analysis of glomerular integrity. Conclusions Ethanolic extracts of T. arjuna supplementation found to be beneficial against high fat induced renal alterations in terms of functions and architecture.

Objectives Preeclampsia (PE) remains the major cause for maternal and foetal mortality and morbidity. Invasion of endovascular trophoblast and remodelling of spiral artery are crucial actions of normal placental development. Non-fulfilment of these processes plays a leading role in the development of preeclampsia. Vascular endothelial growth factor (VEGF) is produced by extravillous trophoblastic tissue and decidual cell population is a well-known angiogenic growth which plays a fundamental role in placental pathogenesis of PE. Annexin A2 (ANXA2) is a profibrinolytic protein receptor required for plasminolysis, which is an important step in the formation of new blood vessel along with VEGF. Role of ANXA2 is poorly studied in context with human reproductive disease like preeclampsia. The purpose of the present study is to examine the expression and association of VEGF and ANXA2 in the term placentas of pregnancies with and without PE. Methods The study group comprised of placental tissues procured from gestations with PE (n=30) and without (n=20) PE. The expression of VEGF and ANXA2 in the placental villous tissue was evaluated quantitatively by means of IHC, western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Results Our IHC, western blotting and RT-PCR analysis illustrated the significant decrease in the expression of VEGF and ANXA2 in PE group compared with the normotensive control group (p<0.005). We observed statistically significant positive correlation among the expression of ANXA2 and VEGF in placentas of normotensive control group (p<0.0001). Conclusions The diminished expression of VEGF and ANXA2 in placenta may be associated with the defective angiogenesis and which may possibly play a vital role in PE pathogenesis.

Objectives The present work was designed to study the modulatory effects of algogen-induced vasosensory reflex responses on short-term heart rate variability (HRV) parameters in naïve and vagotomized rat models. Methods In this study, vasosensory reflex responses were elicited by instilling algogens (bradykinin/histamine), a component of inflammatory mediators into a local segment of medium-sized peripheral blood vessel (femoral artery) while a continuous electrocardiogram (ECG) was recorded. Short-term (5 min) ECG segments obtained from original recordings were examined in detail and relevant data of HRV parameters were pooled. Time domain and frequency domain analyses were performed using dedicated software (LabChart 8, AD Instruments ® , Australia) and results were analyzed. Results Bradykinin-induced vasosensory reflexes caused significant alterations in both time domain and frequency domain HRV parameters as compared to the time-matched saline control group. Instillation of bradykinin caused a transient increase in NN interval, RMSSD, TSP, HF power (HFP) along with a decrease in the standard deviation of all normal NN intervals (SDNN), SDNN/RMSSD, LF power (LFP), LFP/HFP. Histamine produced a similar pattern of responses, but HRV alterations were less pronounced compared to those with bradykinin. Further analysis revealed that algogen-induced vasosensory reflex responses caused an increase in the parasympathetic influence on the heart accompanied by a decrease in sympathetic influence. In addition, HRV modulation by algogen-induced vasosensory reflexes was significantly attenuated in vagotomized rats, illustrating the principal role of vagus in the reflex HRV modulation. Conclusions The present study proposes a novel hypothesis regarding the cardio-protective role of inflammatory mediators during acute stress, by potentiating the vagal impact and attenuating the sympathetic impact on the heart.

Objectives Poor sleep is a vital symptom observed in many psychiatric conditions and is the most neglected and underdiagnosed. The current study aims at assessment of sleep quality among psychiatric patients using the Pittsburgh Sleep Quality Index (PSQI) scale and to identify the predictors of sleep quality. Methods A hospital-based cross-sectional observational study conducted in the Psychiatry department with a sample size of 256 patients for six months. PSQI scale was used to assess sleep quality and multiple logistic regression was used (to identify) the predictors for poor sleep quality. Results The mean age of the study population was 37.95 ± 14.11 years, with 148 (58%) male study participants. 192 (75%) of the study population had poor sleep quality with respect to PSQI scale with a mean score of 9.05 ± 4.65 that was well above the expected range (0–5) suggestive of compromised quality of sleep (p=0.001). Poor sleep satisfaction, waking up after the sleep onset, anorexia, day time drowsiness and at least one completely sleepless night in the past one week of admission were identified as good predictors for poor sleep quality. Conclusions Our study addresses the importance of assessing sleep quality regardless of the psychiatric conditions. We recommend screening patients if they have Poor sleep satisfaction, waking up after the sleep onset, anorexia, day time drowsiness or at least one completely sleepless night in the past one week of admission predictors for comorbid sleep disorders.

Objectives Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an adjunct in the vasculitis induction. However, to date, none has established the effect of OVA and LPS in disease induction. Therefore, in the present study, an attempt has been made to develop a new animal model for vasculitis using OVA/LPS in rats. Methods A total of 42 Wistar rats were divided randomly into seven groups (n=6/group), normal control, and three different doses (0.5, 1, and 5 mg/kg) of OVA and LPS treated groups. Half of the rats in each group received only intraperitoneal sensitization, while the remaining half rats were additionally subjected to a one-week intranasal challenge. Results Results showed that both OVA/LPS in their respective groups have significantly increased circulating inflammatory cells, C-reactive protein (CRP), Inflammatory cytokines (IL-1β, IL-6, TNF-α), Kidney damage markers (BUN, Creatinine), and liver function enzymes (AST, ALT) in a dose-dependent manner. Conclusions OVA/LPS induced vascular inflammation in a dose-dependent manner. However, the higher (5 mg/kg) dose of ovalbumin and lipopolysaccharide has contributed to severe vascular inflammation through increasing inflammatory cytokines. These findings suggest that OVA/LPS may contribute as a possible model for vasculitis in rats.

Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model. Highlights – Subchronic (1,000 µg/kg) and chronic (100 µg/kg) dexamethasone exposure act similarly. – These doses improve glucose tolerance and increase triglyceridemia. – The aforementioned doses increase blood pressure and heart rate. – Subchronic (1,000 µg/kg) and chronic (100 µg/kg) dexamethasone cause renal impairment – Subchronic dexamethasone administration at the dose of 1,000 µg/kg cause oxidative stress

Objectives Obesity and related diseases have become one of the most important health problems in the modern age. In addition to its clinical use in the treatment of obesity, bariatric surgery reduces obesity-induced inflammation. Neutrophil–lymphocyte ratio (NLR) is a cheap and easily attainable inflammatory marker. The purpose of this study is to show the effect of bariatric surgery on NLR at preoperative and postoperative 3rd, 6th, and 12th months after SG. Methods 298 patients, who underwent sleeve gastrectomy (SG) in general surgery clinic between 2015 and 2017, were included in the study. We excluded the patients younger than 18 years old, and did not have any inflammatory, infectious, hematological, and comorbide diseases such as diabetes mellitus, cardiovascular diseases, ischemic heart disease, hypertension, renal insufficiency, cancer, and respiratory problems like asthma, obstructive sleep apnea syndrome. We evaluated the levels of NLR at preoperative and postoperative 3rd, 6th, and 12th months visits. Results There were a total of 298 adult patients (age: mean 38.6, minimum 18, maximum 69 years old). Of whom 247 were female (82.9%) and 51 were male (17.1%). We found that NLR levels decreased significantly at 3rd, 6th, and 12th month visits after SG (p<0.001). Conclusions We concluded that NLR levels decrease after surgery in a proportional reduction in adipose tissue. The decrease in NLR levels may also be associated with the protective effects of sleeve gastrectomy against low-grade inflammation-related diseases.

Objectives Nod-like receptor pyrin domain containing 3 (NLRP3) is one of the well characterized inflammasome that controls the maturation of pro-inflammatory cytokines and thereby the inflammation in pancreas which could be a promising target for anti-inflammatory drugs. The present study is aimed to explore whether luteolin can target the NLRP3 inflammasome and modulate its activity through the signaling protein, HSP70 in the ethanol-cerulein model of experimental pancreatitis. Methods Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats received normal diet. Groups 3 and 4 rats received isocalorically adjusted diet containing ethanol for 5 weeks and cerulein (20 μg/kg body weight i.p., thrice weekly for the last 3 weeks of the experimental period). Additionally, group 2 and 4 rats received 2 mg/kg body weight of luteolin orally from third week. Results Luteolin co-administration decreased the serum levels of HSP70, oxidative stress markers, myeloperoxidase, GSH/GSSG and GST with concomitant downregulation in the mRNA expression of HSP70, caspase-1, ASC-NLRP3 and NF-κB. Spearman’s rank correlation test showed that serum HSP70 has positive correlation with the expression of ASC-NLRP3, caspase-1, NF-κB and 4-hydroxynonenal and negative correlation with GSH:GSSG ratio. Conclusions The modulating effect of luteolin on the expression of HSP70, NF-κB and thereby on ASC-NLRP3 complex may be claimed for its pancreato-protective activity.

One of the cancer-related deaths is gastric cancer in this area. Onosma dichroanthum Boiss. roots have been used as an antiseptic and anti-inflammatory for wound healing treatment. The aim of this study was to assess the in vitro cytotoxic and anticancer effects of O. dichroanthum Boiss . roots from the Golestan province of Iran. After identification of the taxonomical effect of O. dichroanthum Boiss., different concentrations of the hydroalcoholic root extract were used. Three different time periods (24, 48, and 72 h) were used to treat AGS gastric cancer and L-929 normal fibroblasts cell lines. The evaluation of different concentrations of root extract was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The 48 h treatment affected cell survival, while the concentration of 64 μg/mL was determined as IC 50 concentrations at 48 h incubation time. The 48 h incubation time with 64 μg/mL showed the best effectiveness on cancerous cell-line while being safe for normal cell-line. Our results show that O. dichroanthum Boiss. roots extract may have cytotoxic and safe effects on gastric cancer cell-line and normal cells in 48 h treatment periods, respectively. The results indicated the O. dichroanthum Boiss. may be as an effective anticancer agent (gastric cancer).

Objectives Quantitative computed tomography (QCT) is a promising tool for objective assessment of interstitial lung disease (ILD) related to connective tissue diseases (CTD). However, its validity was never investigated. The aim of this study was to assess QCT feasibility, face, and content validity evaluation concerning CTD-ILD. Methods A rheumatologist and a chest radiologist conceived an online survey with nine statements: Two about general issue involving CTD-ILD, one for the face validity, three both for content validity and feasibility. Each statement had to be rated with a score from 0 to 100, respectively, (complete disagreement and agreement). We considered a statement supported by the experts if the median score was ≥75.0. Results A panel of 14 experts (11 from Europe, three from America) with a nine years median experience was enrolled. All the statements about feasibility, face and content validity were supported, except for QCT capability to recognize elementary lesions. Conclusions The panel of experts supported feasibility, face, and content validity of QCT assessment concerning CTD-ILD. This may stimulate a greater use in clinical practice and further studies to confirm its discriminative properties and its construct validity.

Objectives Warfarin is the most widely used anticoagulant in the world, but it has several limitations including its narrow therapeutic range, need for dose adjustment and high potential for interactions. The simultaneous use of other drugs or even medicinal plants and certain foods could interfere with its therapeutic activity. In this context, this study aims to investigate the in vitro anticoagulant potential and phytochemical constitution of 17 plants selected from a previous clinical cross-sectional study (2014), that investigated the habits of plant utilization among patients taking warfarin. Methods Ethanol extracts and essential oils were evaluated, in vitro , as to their effect in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Four species that presented aPTT >50 s were selected for phytochemical evaluation. Results Thirteen of the 17 plants selected demonstrated a significant anticoagulant effect in at least one of the evaluated parameters. Citrus sinensis (PT=14.75 and aPTT=53.15), Mentha crispa (aPTT=51.25), Mikania laevigata (PT=14.90 and aPTT=52.10), and Nasturtium officinale (aPTT=50.55) showed greater anticoagulant potential compared to normal plasma pool (PT=12.25 and aPTT=37.73). Chemical profiles of these four species were obtained, and certain compounds were identified: rosmarinic acid from M. crispa and isoorientin from N. officinale . Conclusions Thus, the results of this study could be a useful indicator for clinical practice towards the possibility of interaction between these plants and anticoagulants, although further clinical research is needed taking into consideration the limitations of in vitro studies. These findings also suggest that further research into the action of these plants could be of real clinical value in identifying potential alternative anticoagulant therapies.

Objectives The aim of this study was to determine normative electrophysiological reference values of median sensory nerve conduction studies among security guards with the palmaris longus tendon (PLT). Methods Sensory nerve conduction studies of the median nerve using antidromic and orthodromic methods were conducted in the upper limbs of 101 healthy male security guards between the ages of 21 and 42 years. The presence of the PLT was recorded in both hands using a standard test. A scatter plot was used to determine the correlation between different parameters using the ortho and antidromic methods. Results The mean age (years), weight (kg), height (cm), and BMI (kg/m2) were 28.77 ± 5.14, 70.53 ± 11.28, 171.71 ± 7.12, and 23.91 ± 3.45, respectively. In the median nerve (sensory) by antidromic method, the mean distal latency (DL) was 2.65 ± 0.33 ms and 2.64 ± 0.37, SNCV (sensory nerve conduction velocity) was 53.45 ± 5.28 m/s and 53.84 ± 5.68 and the amplitude was 27.33 ± 12.38 µV and 29.41 ± 12.97 in the left- and right-hand wrist, respectively. By orthodromic method the DL was 2.54 ± 0.53 ms and 2.51 ± 0.44, SNCV was 55.93 ± 6.09 m/s and 55.93 ± 5.24 and the sensory nerve action potential amplitude was 12.00 ± 8.82 µV and 11.72 ± 6.24 in the left and right hand, respectively. Spearman correlations were used to determine the variables influenced by hand sidedness. Conclusions The normative reference parameters of sensory nerve conduction velocity of the median nerve were established by both methods using a standardized technique.

Objectives Chemokine receptor antagonists are being explored for their therapeutic potential in various disease processes. As the chemokine (C–C motif) receptor 2 (CCR2) antagonist RS504393 is known to compete with ligand binding to α 1 -adrenoceptors, we tested a panel of 10 CCR antagonists for interactions with α 1 -adrenoceptors to evaluate potential cardiovascular activities and side-effect profiles. Methods The PRESTO-Tango β-arrestin recruitment assay was utilized to test whether the CCR antagonists interfere with α 1b -AR activation upon stimulation with phenylephrine. Pressure myography with isolated rat resistance arteries was employed to assess their effects on phenylephrine-induced vasoconstriction. The following antagonists were tested: CCR1–BX471, BX513, BI639667; CCR2–RS504393, INCB3284; CCR3–SB328437; and CCR4–AZD2098, and C021; CCR5–Maraviroc; CCR10-BI6901. The pan-α 1 -adrenoceptor antagonist prazosin was used as control. Results Among the CCR antagonists tested, RS504393, BX513, and C021 inhibited phenylephrine-induced β-arrestin recruitment to α 1b -adrenoceptor and phenylephrine-induced vasoconstriction. While RS504393 functioned as a competitive α 1 -adrenoceptor blocker, BX513 and C021 functioned as noncompetitive α 1 -adrenoceptor antagonists in both assay systems. Furthermore, RS504393, BX513, and C021 dose-dependently dilated arteries that were fully preconstricted with phenylephrine. Conclusions Our data suggest that CCR antagonists should be screened for cross-reactivity with α 1 -adrenoceptors to exclude potential adverse cardiovascular effects when used as anti inflammatory drugs.