In vivo tracking of human adipose-derived stem cells labeled with ferumoxytol in rats with middle cerebral artery occlusion by magnetic resonance imaging

Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except I day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem ceils compared with T2-weighted imaging in routine MRI.

Involvement of TRPC1 and Cyclin D1 in Human Pulmonary Artery Smooth Muscle Cells Proliferation Induced by Cigarette Smoke Extract

Cigarette smoking contributes to the development of pulmonary artery hypertension(PAH).As the basic pathological change of PAH,pulmonary vascular remodeling is considered to be related to the abnormal proliferation of pulmonary artery smooth muscle cells(PASMCs).However,the molecular mechanism underlying this process remains not exactly clear.The aim of this research was to study the molecular mechanism of PASMCs proliferation induced by smoking.Human PASMCs(HPASMCs)were divided into 6 groups:0%(control group),cigarette smoking extract(CSE)-treated groups at concentrations of 0.5%,1%,2%,5%,10%CSE respectively.HPASMCs proliferation was observed after 24 h.HPASMCs were divided into two groups:0(control group),0.5%CSE group.The mRNA and protein expression levels of transient receptor potential channel 1(TRPC1)and cyclin D1 in HPASMCs after CSE treatment were respectively detected by RT-PCR and Western blotting.The intracellular calcium ion concentration was measured by the calcium probe in each group.In the negative control group and TRPC1-siRNA transfection group,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein were detected.Data were compared with one-way ANOVA(for multiple-group comparison)and independent t-test(for two-group comparison)followed by the least significant difference(LSD)test with the computer software SPSS 17.0.It was found that 0.5%and 1%CSE could promote the proliferation of HPASMCs(P<0.05),and the former was more effective than the latter(P<0.05),while 3%and above CSE had inhibitory effect on HPASMCs(P<0.05).The mRNA and protein expression levels of TRPC1 and cyclin D1 in 0.5%and 1%CSE groups were significantly higher than those in the control group(P<0.05),while those in 3%CSE group were significantly decreased(P<0.05).Moreover,the proliferation of HPASMCs and the expression of cyclin D1 mRNA and protein in TRPC1-siRNA transfection group were significantly reduced as compared with those in the negative control group(P<0.05).It was concluded that low concentration of CSE can promote the proliferation of HPASMCs,while high concentrations of CSE inhibit HPASMCs proliferation.These findings suggested that CSE induced proliferation of HPASMCs at least in part via TRPC1-mediated cyclin D1 expression.

Characterization of optimal resting tension in human pulmonary arteries

AIM To determine the optimum resting tension(ORT) for in vitro human pulmonary artery(PA) ring preparations.METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution(Krebs).The pulmonary arteries were then cut into 2 mm long rings.PA rings were mounted in 25 m L organ baths or 8 m L myograph chambers containing Krebs compound(37 ℃,bubbled with 21% O_2:5% CO_2) to measure changes in isometric tension.The resting tension was set at 1-gram force(gf) with vessels being left static to equilibrate for duration of one hour.Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf.Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension(1.2,1.4,1.6,1.8 and 2.0 gf).RESULTS Twenty PA rings of internal diameter between 2-4 mmwere prepared from 4 patients.In human PA rings incrementing the tension during rest stance by 0.6 gf,up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension.Further enhancement of active tension by 0.4 gf,up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction.Both Myograph and the organ bath demonstrated identical conclusions,supporting that the radial optimal resting tension for human PA ring was 1.61 g.CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf(15.78 m N) for human PA rings.

Morphometric Studies of Human Coronary Artery Trees in Healthy and Disease

Objective According to the report from American Heart Association(AHA),cardiovascular diseases(CVDs)are the leading causes of death globally,and coronary artery disease(CAD),known as coronary atherosclerotic plaques,accounts for over 30%of cardiovascular diseases.Therefore,it is of great clinical significance to study the relationship between coronary bifurcations morphometrical feature change and coronary artery disease.Although coronary atherosclerosis has been extensively investigated,there is a lack of in-deep study on the differences in morphometric features between optimal and realistic geometry of coronary arterial trees.The purpose of the present paper is to determine the morphological changes in patients with CAD lesion compared with non-coronary artery disease(non-CAD)subjects.Methods Due to the difficulty of studying the coronary bifurcations in vivo,image-based in vitro anatomical 3D models have been widely used as a noninvasive method for morphometric measurement and clinical diagnosis of the coronary bifurcations.With the development of coronary computed tomography angiography(CTA)hardware and software technologies,the CTA imaging technique has been shown a promising application in the characterization,visualization,and identification of coronary artery disease in recent decades.The CTA images used to reconstruct three-dimensional(3D)coronary arterial trees are from Asia populations(Southern Chinese populations),including five cadavers without CAD lesion and 102 patients with CAD lesion.The best fit artery diameter was calculated as twice the average radius between the points in the centerlines and the points on the coronary arterial inner wall.The bifurcation angles between larger daughter artery and smaller daughter artery were determined by the intersection angle of their centerlines.Murray’s law was introduced to assess the deviation of the realistic vascular networks from its optimal state.Results Based on the morphometric analysis of coronary artery bifurcations in non-CAD subjects and patients with CAD lesion subjects,the most important finding is that morphological feature parameters of non-CAD subjects are closer to the optimal values than those of patients with CAD lesion.Moreover,by comparing the morphometric data between the left and right coronary arteries,the right coronary artery exhibits a structure closer to the optimal one in morphological feature than the left coronary artery.In addition,coronary arterial trees with CAD lesion have higher asymmetry and larger area expansion ratio(AER)than those of the coronary arterial trees without CAD lesion.Conclusions We morphologically found that the coronary arterial trees with CAD lesion and left are more likely to deviate from the optimal structure predicted by Murray’s law than those without CAD lesion and right.The degree to which coronary arterial system deviating from their optimal state may directly affect the incidence of coronary artery disease.This computer morpho-logical analysis strategy is illustrated to be effective in the distinguishing of the geometric differences between the healthy and diseased coronary arteries,and the analysis method may have a large potential in cardiovascular disease earlier diagnosis.

Human umbilical artery smooth muscle exhibits a 2-APBsensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca^(2+)stores the capacitative response triggers an extracellular Ca^(2+)influx through store-operated channels(SOCs)which refills these stores.Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin-and histamine-induced contractions.Intracellular Ca^(2+)depletion by a Ca^(2+)-free extracellular solution followed by Ca^(2+)readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate(2-APB),suggesting a capacitative response.In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one,likely because 2-APB inhibited store refilling by capacitative Ca^(2+)entry.2-APB inhibition of sarcoplasmic reticulum Ca^(2+)release was excluded because this blocker did not affect serotonin force development in a Ca^(2+)-free solution.The PCR technique showed the presence of mRNAs for STIM proteins(1 and 2),for Orai proteins(1,2 and 3)and for TRPC channels(subtypes 1,3,4 and 6)in the smooth muscle of the human umbilical artery.Hence,this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

Pulmonary arterial hypertension related to human immunodeficiency virus infection:A case series

AIM: To present 18 new cases of human immunodeficiency virus(HIV)-related pulmonary arterial hypertension(PAH) with presenting features,treatment options and follow-up data.METHODS: This is a single-centre,retrospective,observational study that used prospectively collected data,conducted during a 14-year period on HIV-related PAH patients who were referred to a pulmonary hy-pertension unit. All patients infected with HIV were consecutively admitted for an initial evaluation of PAH during the study period and included in our study. Right heart catheterisation was used for the diagnosis of PAH. Specific PAH treatment was started according to the physician's judgment and the recommendations for idiopathic PAH. The data collected included demographic characteristics,parameters related to both HIV infection and PAH and disease follow-up.RESULTS: Eighteen patients were included. Intravenous drug use was the major risk factor for HIV infection. Risk factors for PAH,other than HIV infection,were present in 55.5% patients. The elapsed time between HIV infection and PAH diagnoses was 12.2 ± 6.9 years. At PAH diagnosis,94.1% patients had a CD4 cell count > 200 cells/μL. Highly active antiretroviral therapy(present in 47.1% patients) was associated with an accelerated onset of PAH. Survival rates were 93.8%,92.9% and 85.7% at one,two and three years,respectively. Concerning specific therapy,33.3% of the patients were started on a prostacyclin analogue,and the rest were on oral drugs,mainly phosphodiesterase-5 inhibitors. During the follow-up period,specific therapy was de-escalated to oral drugs in all of the living patients.CONCLUSION: The survival rates of HIV-related PAH patients were higher,most likely due to new aggressive specific therapy. The majority of patients were on oral specific therapy and clinically stable. Moreover,sildenafil appears to be a safe therapy for less severe HIVrelated PAH.

Oxidative modification of high density lipoprotein induced by cultured human arterial smooth muscle cells

Objective: To observe the oxidative modification of high density lipoprotein (HDL) induced by cultured human arterial smooth muscle cells (SMCs). Methods: HDL cocultured with SMCs at 37℃ in 48 h was subjected, and native HDL (N-HDL) served as control. Oxidative modification of HDL was identified by using agarose gel electrophoresis. Absorbances of conjugated diene (CD) and lipid hydroperoxide (LOOH) were measured with ultraviolet spectrophotometry at 234 and 560 nm respectively, and fluorescence intensity of thiobarbuturic acid reaction substance (TBARS) with fluorescence spectrophotometry at 550 nm emission wavelength with excitation at 515 nm. Results: In comparison with N-HDL, the electrophoretic mobility of SMCs-cocultured HDL was increased, and the contents of CD, LOOH and TBARS HDL were very significantly higher than those of the control HDL (P<0.01). Conclusion: Oxidative modification of HDL can be induced by human arterial SMCs.

Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain

Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.

Diagnosis and management of fibromuscular dysplasia and segmental arterial mediolysis in gastroenterology field: A mini-review

The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia(FMD) and segmental arterial mediolysis(SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.

Pseudoaneurysm of gastroduodenal artery following radical gastrectomy for gastric carcinoma patients

We report a rare case of postoperative pseudoaneurysm of the gastroduodenal artery following radical gastrectomy.Surgical trauma to the gastroduodenal artery during regional lymphadenectomy was considered as the cause of the postoperative pseudoaneurysm. The pseudoaneurysm was successfully managed by ligating the bleeding vessel. We should consider the possibility of pseudoaneurysm formation in a patient with gastrointestinal bleeding in the postoperative period following radical gastrectomy with regional lymph node and perivascular lymphatic dissection.

Aggressive restenosis after percutaneous intervention in two coronary loci in a patient with human immunodeficiency virus infection

A 54-year-old black African woman, 22 years human immunodeficiency virus(HIV)-positive, presented with an acute coronary syndrome. She was taking two nucleoside reverse transcriptase inhibitors and two protease inhibitors. Viral load and CD4 count were stable. Angiography revealed a right coronary artery lesion, which was treated with everolimus eluting stent. She also underwent balloon angioplasty to the first diagonal. She re-presented on three different occasions and technically successful coronary intervention was performed. The patient has reported satisfactory compliance with dual anti platelet therapy throughout. She was successfully treated with surgical revascularisation. The patient did not experience any clinical recurrence on follow up. This case demonstrates exceptionally aggressive multifocal and recurrent instent restenosis in a patient treated for HIV infection, raising the possibility of an association with HIV infection or potentially components of retro viral therapy.

Mesenteric Ischemia:An unusual presentation of fistula between superior mesenteric artery and common hepatic artery

Chronic mesenteric ischemia is an uncommon condition associated with a high morbidity and mortality.We reported a 36-year old women with postprandial abdominal pain due to chronic mesenteric ischemia caused by a fistula between superior mesenteric and common hepatic artery.

Dissecting molecular mechanisms underlying ferroptosis in human umbilical cord mesenchymal stem cells:Role of cystathionineγ-lyase/hydrogen sulfide pathway

BACKGROUND Ferroptosis can induce low retention and engraftment after mesenchymal stem cell(MSC)delivery,which is considered a major challenge to the effectiveness of MSC-based pulmonary arterial hypertension(PAH)therapy.Interestingly,the cystathionineγ-lyase(CSE)/hydrogen sulfide(H_(2)S)pathway may contribute to mediating ferroptosis.However,the influence of the CSE/H_(2)S pathway on ferroptosis in human umbilical cord MSCs(HUCMSCs)remains unclear.AIM To clarify whether the effect of HUCMSCs on vascular remodelling in PAH mice is affected by CSE/H_(2)S pathway-mediated ferroptosis,and to investigate the functions of the CSE/H_(2)S pathway in ferroptosis in HUCMSCs and the underlying mechanisms.METHODS Erastin and ferrostatin-1(Fer-1)were used to induce and inhibit ferroptosis,respectively.HUCMSCs were transfected with a vector to overexpress or inhibit expression of CSE.A PAH mouse model was established using 4-wk-old male BALB/c nude mice under hypoxic conditions,and pulmonary pressure and vascular remodelling were measured.The survival of HUCMSCs after delivery was observed by in vivo bioluminescence imaging.Cell viability,iron accumulation,reactive oxygen species production,cystine uptake,and lipid peroxidation in HUCMSCs were tested.Ferroptosis-related proteins and S-sulfhydrated Kelchlike ECH-associating protein 1(Keap1)were detected by western blot analysis.RESULTS In vivo,CSE overexpression improved cell survival after erastin-treated HUCMSC delivery in mice with hypoxiainduced PAH.In vitro,CSE overexpression improved H_(2)S production and ferroptosis-related indexes,such as cell viability,iron level,reactive oxygen species production,cystine uptake,lipid peroxidation,mitochondrial membrane density,and ferroptosis-related protein expression,in erastin-treated HUCMSCs.In contrast,in vivo,CSE inhibition decreased cell survival after Fer-1-treated HUCMSC delivery and aggravated vascular remodelling in PAH mice.In vitro,CSE inhibition decreased H_(2)S levels and restored ferroptosis in Fer-1-treated HUCMSCs.Interestingly,upregulation of the CSE/H_(2)S pathway induced Keap1 S-sulfhydration,which contributed to the inhibition of ferroptosis.CONCLUSION Regulation of the CSE/H_(2)S pathway in HUCMSCs contributes to the inhibition of ferroptosis and improves the suppressive effect on vascular remodelling in mice with hypoxia-induced PAH.Moreover,the protective effect of the CSE/H_(2)S pathway against ferroptosis in HUCMSCs is mediated via S-sulfhydrated Keap1/nuclear factor erythroid 2-related factor 2 signalling.The present study may provide a novel therapeutic avenue for improving the protective capacity of transplanted MSCs in PAH.

Variations in the Course of the Inferior Gluteal Nerve and Artery: A Case Report and Literature Review

Variations in the course of the inferior gluteal nerve and artery were observed in Japanese cases (4/94 sides). In these variation cases, the inferior gluteal nerve exited the pelvis from the upper edge of the piriformis (suprapiriformis foramen) in 4/4 sides (4.26%). In 2/4 sides (2.13%), the normal inferior gluteal artery was not observed, except that a fine artery exited the pelvis from the inferior piriformis foramen to form an “arch” with the superior gluteal artery under the gluteal maximus in 1/4 side. Moreover, in 1/4 side, a twig of the internal pudendal artery exited pelvis from inferior piriformis foramen and distributed to the surrounding tissues. The present observations of the inferior gluteal nerve and artery course are very important and useful for surgeons and nurses.

Rhizoma Chuanxiong regulates vascular endothelial growth factor production in hypoxic human umbilical vein endothelial cells in vitro and in peri-infarct rat brain tissue

BACKGROUND： Vascular endothelial growth factor （VEGF） acts as ＂molecular bridge＂ following ischemic stroke to improve and restore blood supply and reduce infarction volume. Clinical studies have demonstrated the efficacy of Rhizoma Chuanxiong （Chuanxiong） in the treatment of ischemic cerebrovascular diseases. However, whether it promotes endogenous VEGF expression in ischemic stroke remains unknown. OBJECTIVE： To investigate the influence of Rhizoma Chuanxiong on VEGF production in vitro cultured human umbilical vein endothelial cells and on VEGF expression in ischemic cerebral tissues to explore its role in angiogenesis. DESIGN, TIME AND SETTING： In vitro basic comparison of traditional Chinese drug-containing serum pharmacology; in vivo randomized, controlled, animal experiment. This study was performed at the Medical Laboratory of West China Hospital, Sichuan University between December 2002 and April 2004. MATERIALS： Two Chinese rabbits were selected. One was intragastrically perfused with 5.8 g/kg Rhizoma Chuanxiong extract twice per day for three consecutive days to prepare Rhizoma Chuanxiong extract-containing serum. The remaining rabbit was intragastrically perfused with the same volume of normal saline twice per day for three consecutive days. Rhizoma Chuanxiong extract was provided by Beijing Traditional Chinese Medicine Research Institute, predominantly composed of ligustrazine, ligustilide, and ferulic acid. ChemiKineTM human VEGF Kit was purchased from Chemicon, USA; mouse anti-VEGF monoclonal antibody and biotin-goat anti-mouse IgG were purchased from Santa Cruz Biotechnology. Inc., USA. METHODS： （1） In vitro experiment： in vitro cultured human umbilical vein endothelial cells were separately incubated in rabbit serum with 10% Rhizoma Chuanxiong extract, normal medium without rabbit serum, and rabbit serum without Rhizoma Chuanxiong extract （blank control）. In addition, cells from the three groups were incubated under normoxia （5% CO2, 95% air） and hypoxia （1% 02, 5% CO2, 94% N2）, respectively, for 24 hours. （2） In vivo experiment： a total of 4/44 Sprague Dawley rats were selected for the sham-operated group （no occlusion）, and the remaining rats were used to establish a cerebral ischemiaJreperfusion model by suture occlusion. 32 animals with ischemia/reperfusion injury were randomly divided into treatment and model groups, with 16 rats in each group. Both groups were intraperitoneally infused with 0.58 g/kg Rhizoma Chuanxiong extract and normal saline two hours following reperfusion. The sham-operated group was administrated normal saline. Animals were treated with saline or Chuanxiong extracts （0.58 g/kg） twice per day for three consecutive days. MAIN OUTCOME MEASURES： In vitro experiment： VEGF concentration was detected in each group by enzyme-linked immunosorbent assay. In vivo experiment： behavioral alterations of rats were evaluated by neurological function scale; infarct volume was assessed by hematoxylin-eosin staining; VEGF protein expression in the infarct regions was determined by immunohistochemistry. RESULTS： （1） VEGF levels were similar between the three groups under normexic condition （P 〉 0.05）; while hypoxia induced VEGF production （P 〈 0.01 ）. VEGF levels in the drug-containing serum group were particularly higher compared with the other groups （P 〈 0.01）. （2） Compared with normal saline treatment, Rhizoma Chuanxiong extract significantly improved the neurological scale and reduced cerebral infarct volumes （P〈 0.05）. The percent of VEGF-positive cells was significantly greater than the model group （P 〈 0.05）. The sham-operated group exhibited normal neurological function, with no infarct focus. CONCLUSION： Rhizoma Chuanxiong extract-containing rabbit serum effectively promoted cultured VEGF production under hypoxia. Rhizoma Chuanxiong extract upregulated VEGF expression in the infarct region, improved neurological function, and reduced infarct size.

Cardiometabolic Phenotype and Arterial Stiffness in HIV-Positive Black African Patients

Objective: To test the hypothesis that Human Immunodeficiency Virus (HIV) infection in Black patients is associated with increased cardiometabolic risk factors that may increase aortic stiffness assessed by pulse wave velocity (PWV). Methods: We matched 96 Cameroonian Controls to 238 (Un) treated HIV-positive patients [HIV] for age. In each participant, aortic PWV (ComplioR), blood pressures (BP), lipid profile and fasting blood glucose (FPG) were measured. Results: Waist circumference was lower in HIV than in Controls (both p g·dl-1), and of diabetes (FPG > 125 mg·dl-1) were higher in HIV than in the Controls (50% vs 27%, and 23% vs 1%, respectively;both p < 0.0001). HDL-C was lower in HIV as compared to the Control (p = 0.02). Fasting triglycerides (TG) and the atherogenic dyslipidemia ratio [log(TG)/HDL-C] were higher in HIV than in the Controls (both p < 0.05). Hypertension prevalence was high but comparable in the two groups (48% vs 44% respectively, p > 0.05). HIV patients exhibited a twice-higher prevalence of MetS (AHA/NHLBI score 33/5) than that of the Controls (41% vs 21%;p 0.01). Similarly, severity of MetS phenotype was higher in HIV as compared to the Controls (2.14% vs 1.59%;p < 0.0001). PWV adjusted for age, mean BP and gender was faster in HIV in comparison to the controls (7.33 m/s vs 6.86 m/s, respectively;p = 0.036). Conclusions: HIV infection is associated with higher prevalence of MetS and its phenotype in Black African patients that may induce increased aortic stiffness.

<i>In Vitro</i>Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.

Opiate exposure increases arterial stiffness, advances vascular age and is an independent cardiovascular risk factor in females: A cross-sectional clinical study

Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by radial arterial tonometry (SphygmoCor) in female control and opiate-dependent patients and compared to lifetime opiate use. Results: 222 opiate dependent women were compared to 175 controls. Opiate dependent patients were receiving treatment with buprenorphine (83.3%), methadone (13.5%), or naltrexone (3.2%). Non log transformed chronologic age (CA) for the two groups was 33.58 ± 0.57 (opiate) vs. 32.62 ± 0.96 (controls) years (mean ± S.E.M.;P = 0.39). Vascular Reference Age (RA) 39.30 ± 1.28, vs. 35.03 ± 1.41 the RA-CA difference (5.73 ± 1.02 vs. 2.41 ± 0.91) and the RA/CA ratio (1.16 ± 0.03 vs. 1.07 ± 0.02;all P < 0.02), and all measurements of central arterial stiffness (P < 0.02) were significantly worse for opiates compared to controls. When adjusted for CA, RA and central augmentation pressure and index were all worse by themselves and in interaction with CA (all P < 0.005). At 60 years the modelled RA’s were 83.79 and 67.52 years respectively. The opiate dose-duration interaction showed a dose-response effect with RA (P = 0.0033). After full adjustment for established cardiovascular risk factors, the dose-duration interaction remained significant (P = 10-6), was included in 10 other terms, and dose or duration was included in 15 other interactions. Conclusion: These data show that lifetime opiate use is significantly associated with increased arterial stiffness and vascular age and suggest a dose-response relationship. This relationship is robust and persists after full multivariate adjustment. These findings carry far-reaching implications for opiate-induced generalized acceleration of organismal ageing.

Conservative management of cervical pregnancy: The utility of methotrexate treatment and uterine artery embolization

The aim of this retrospective case series report is to evaluate systemic methotrexate therapy in conjunction with uterine artery embolization (UAE) in the conservative management of cervical pregnancy. We examined clinical presentations, treatments, and therapeutic outcomes in fifteen patients with a cervical pregnancy who wished for preservation of fertility, treated at Okayama University Hospital between 1998 and 2012. Twelve patients received systemic methotrexate including five treated with UAE. One was treated with UAE alone. Two patients received neither UAE nor methotrexate because of a low human chorionic gonadotropin (hCG) level and poor blood flow around the gestational sac (GS). An increased GS size and the elevated hCG level during methotrexate therapy might be risk factors for emergent UAE. Two of six patients treated with UAE had subsequent confirmed viable pregnancies. In patients with a cervical pregnancy, methotrexate therapy in combination with UAE can be considered as an option before performing a hysterectomy with suitable counseling about the risk of loss of fertility. Careful observation of the GS size and hCG level during methotrexate therapy might be important for management.

Effects of terlipressin on systolic pulmonary artery pressure of patients with liver cirrhosis: An echocardiographic assessment

AIM:Portopulmonary hypertension is a serious complication of chronic liver disease.Our aim was to search into the effect of terlipressin on systolic pulmonary artery pressure among cirrhotic patients. METHODS:Twelve patients(6 males and 6 females)with liver cirrhosis were recruited in the study.Arterial blood gas samples were obtained in sitting position at rest.Contrast enhanced echocardiography and measurements of systolic pulmonary artery pressure were performed before and after the intravenous injection of 2 mg terlipressin. RESULTS:Of 12 patients studied,the contrast enhanced echocardiography was positive in 5,and the positive findings in contrast enhanced echocardiography were reversed to normal in two after terlipressin injection.The mean systolic pulmonary artery pressure was 25.5±3.6 mmHg before terlipressin injection,and was 22.5+2.5 mmHg after terlipressin(P=0.003).The systolic pulmonary artery pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin injection,systolic pulmonary artery pressure was<25 mmHg in four of these cases(58.3% vs 25%,P=0.04). CONCLUSION:Terlipressin can decrease the systolic pulmonary artery pressure in patients with liver cirrhosis.