The role of central oxytocin in stress-induced cardioprotection in ischemic-reperfused heart model

Background and purposeThere is growing evidence that stress contributes to cardiovascular disease and triggers the release of oxytocin. Moreover previous studies confirmed oxytocin mimics the protection associated with ischemic preconditioning. The present study was aimed to assess the possible cardioprotective effects of the centrally released oxytocin in response to stress and intracerebroventricular (i.c.v.) administration of exogenous oxytocin in ischemic-reperfused isolated rat heart.Methods and subjectsRats were divided in two main groups and all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed rats [control: vehicle, oxytocin (OT; 100 ng/5 μl), atosiban (ATO; 4.3 μg/5 μl) as oxytocin antagonist, ATO + OT] and stressed rats [St: stress, OT + St, ATO + St]. After anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60 min reperfusion (IR). Acute stress protocol included swimming for 10 min before anesthesia. Myocardial function, infarct size, coronary flow, ventricular arrhythmia, and biochemical parameters such as creatine kinase and lactate dehydrogenase were measured. Ischemia-induced ventricular arrhythmias were counted during the occlusion period.ResultsThe plasma levels of oxytocin and corticosterone were significantly elevated by stress. Unexpectedly hearts of stressed rats showed a marked depression of IR injury compared to control group. I.c.v. infusion of oxytocin mimicked the cardioprotective effects of stress, yet did not elevate plasma oxytocin level. The protective effects of both stress and i.c.v. oxytocin were blocked by i.c.v. oxytocin antagonist.ConclusionsThese findings suggest that i.c.v. infusion of exogenous oxytocin and centrally released endogenous oxytocin in response to stress could play a role in induction of a preconditioning effect in ischemic-reperfused rat heart via brain receptors.     

Mitochondrial D-loop variation in leber hereditary neuropathy patients harboring primary G11778A, G3460A, T14484C mutations: J and W haplogroups as high-risk factors

BACKGROUND: Leber hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. It is caused by three primary point mutations including G11778A, G3460A, and T14484C in the mitochondrial genome. These three mutations account for the majority of LHON cases and affect genes that encode for different subunits of mitochondrial complex I. Mitochondrial DNA (mtDNA) has a non-coding region at the displacement loop (D-loop) that contains two hypervariable segments (HVS-I and HVS-II) with high polymorphism. METHODS: To investigate any possible association between LHON primary mutations and mtDNA haplogroups (hg), the nucleotide sequence of the HVS-I region of mtDNA was determined in 30 unrelated Iranian patients with LHON harboring one of the primary mutations and 100 normal controls with the same ethnicity. DNA was extracted from the peripheral blood after having obtained informed consent. The nucleotide sequence of HVS-I (np 16,024-16,383) was directly determined. RESULTS: Our analysis revealed a relatively high proportion of haplogroup J in LHON patients (53.3%) compared to normal controls (20%). In addition, a slightly significant increase of normal controls of haplogroup L has been confirmed (14% in normal controls vs. 0% in LHON patients at p = 0.03), whereas other haplogroups did not show contribution to LHON contingency. CONCLUSIONS: The analysis presented here provides evidence that there is an association between G11778A and G3460A with haplogroup J (including J1 and J2) and W, respectively. Therefore, we hypothesize that mtDNA haplogroups J (J1 and J2) and W might act as predisposing haplotypes, increasing penetrance of LHON disease.     

Tumoral cell mtDNA approximately 8.9 kb deletion is more common than other deletions in gastric cancer

BACKGROUND: The aim of the study was to clarify the role of deletion of mitochondrial DNA (mtDNA) in gastric carcinogenesis and to determine prevalence of mitochondrial deletions in different regions of tumoral tissue in comparison with adjacent non-tumoral tissue in gastric cancer. METHODS: In order to investigate whether a high incidence of mutations exists in mtDNA of gastric cancer tissues, we screened five regions of the mitochondrial genome by PCR amplification, Southern blot and DNA sequence analysis. RESULTS: Of 71 cancer patients, the approximately 8.9 kb deletion was detected among different deletions in 9 cases (12.67%) of the tumoral tissues and 1 case (1.40%) in non-tumoral tissues that were adjacent to the tumors. Level of the 8.9 kb deletion has been found to be more than other deletions in tumoral tissues. CONCLUSIONS: The approximately 8.9 kb deletion has an obvious correlation with age and histological type. These data suggest that the approximately 8.9 kb deletion in mtDNA may play an important role in gastric carcinogenesis.     

Prevalence of human T-lymphotropic virus type 1 among blood donors from Mashhad,Iran

The city of Mashhad is the capital of Khorasan, the northeastern province of Iran, which has been recognized as an area where human T-lymphotropic virus type 1 (HTLV-1) infection is endemic. All serum samples from blood donors are routinely screened for HTLV-1 by using enzyme-linked immunosorbent assay (ELISA). In the present study, 28,926 donors (81.86% male and 18.14% female) with a mean age of 32 years (range, 18 to 65 years) were screened in a 6 months period (July to December 1999). Of these donors in the primary screening, 228 (0.78%) tested positive by ELISA. The positive samples were confirmed by Western blot (WB) analysis. The WB results indicated that, of 228 positive ELISA specimens, 91.2% (208 specimens) were HTLV-1, 4.82% (11 specimens) were HTLV, 3.5% (8 specimens) were indeterminate, and 0.44% (1 specimen) was not confirmed. HTLV refers to samples in which the complete viral antigen banding patterns on WB strips were not present. In order to further evaluate the detection methodologies used, the HTLV-1-seropositive samples, the indeterminant samples, and/or HTLV samples were examined and confirmed by PCR. The HTLV samples were determined to be HTLV-1, the remaining samples were indeterminant, and the negative sample could not be confirmed for HTLV-1 by PCR. The prevalence of HTLV-1 infection in our study was 0.77% among blood bank donors, which reconfirms the city of Mashhad as an area where the virus is endemic compared to other regions in the world. The incidence was correlated with increasing age, and it was higher in females than in males.     

Contribution of endogenous opioids and nitric oxide to papillary muscle contractile impairment in cholestatic rats

Attenuated responsiveness to adrenoceptor stimulation has been proposed as an important factor underlying cardiovascular complications of cholestasis. We examined isolated papillary muscle responsiveness to alpha (phenylephrine) and beta-adrenoceptor (isoproterenol) agonists in 7-day bile duct-ligated rats. We investigated the role of nitric oxide (NO) and endogenous opioids in papillary muscle hyporesponsiveness to isoproterenol stimulation. In order to evaluate the effect of NO and endogenous opioids, animals were treated with chronic subcutaneous injections of N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) or naltrexone (20 mg/kg/day), or isolated papillary muscles were exposed acutely to the same drugs (10(-4) and 10(-6) M, respectively) in an organ bath. The basal contractile force of papillary muscle, +dT/dtmax and -dT/dtmax, was significantly decreased in bile duct-ligated rats compared to sham-operated ones (P<0.05, for each value). The concentration-response curve for phenylephrine and isoproterenol demonstrated a reduced maximum effect in bile duct-ligated rats compared to the sham-operated group (P<0.01 and 0.05, respectively). Basal contractile abnormalities of bile duct-ligated rats were corrected by L-NAME or naltrexone treatment, either acute or chronic. While chronic L-NAME treatment resulted in a left-ward shift (P<0.05), it had no effect on the maximum effect in bile duct-ligated rats. Acute L-NAME treatment did not influence isoproterenol responsiveness. Acute and chronic naltrexone treatment resulted in partial and complete correction of the hyporesponsiveness of bile duct-ligated rats, respectively (P<0.05). This investigation demonstrates that the papillary muscles of 7-day bile duct ligated-rats have an impaired basal contractility and hyporesponsiveness to both alpha and beta-adrenoceptor stimulation. It also provides evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced cardiac impairment.     

Comparative sensitivity of fluorescent antibody staining of conjunctival scrapings and irradiated McCoy cell culture for the diagnosis of hyperendemic trachoma.

The sensitivity of an indirect fluorescent antibody (FA) staining technique for detecting chlamydial inclusions in scrapings from the whole conjunctiva (upper tarsus, upper fornix, and lower lid) was compared with the sensitivity of culture in irradiated McCoy cells for the diagnosis of hyperendemic trachoma. In a group of 211 patients with various grades of active trachoma from the Bandar Abbas area of Southern Iran 42 patients were positive for chlamydiae by either method. There was little difference between the rates of positivity of FA staining of the scrapings from the whole conjunctiva (28 positives) and culture in irradiated McCoy cells (32 positives). In the patients included in this study chlamydial inclusions were detected in 15 eyes by examination of FA stained scrapings taken from the upper tarsal conjunctiva, whereas inclusions were detected in 40 eyes by the additional examination of scrapings taken from the upper fornix and lower lid (P less than 0.001). The examination of FA stained scrapings taken from the whole conjunctiva and spread as a single but larger smear may provide a satisfactory alternative to cell culture methods for the diagnosis of trachoma, particularly for field studies when cell culture facilities are not available.     

Approach to the acute, generalized, blistering patient

This article discusses the approach to the acute, generalized, blistering patient from the perspective of the dermatologic consultant. Initially, a case is presented, followed by a discussion of the relevant evaluation, differential diagnosis, and treatment options.     

Prenatal Magnetic Resonance Imaging (MRI) Findings of a Foregut Duplication Cyst of the Tongue

Foregut duplication cysts of the oral cavity or lingual choristomas have a potential risk of airway obstruction. Two cases are reported that were initially detected by screening sonography. Further imaging with both static and real‐time cine magnetic resonance imaging confirmed the lingual origin, relationship of the mass to fluid‐filled spaces within the oral cavity, motion of the mass with the tongue during fetal swallowing, and airway patency. The additional information provided by magnetic resonance imaging aided in planning delivery and obviated the need for an ex utero intrapartum treatment procedure because airway patency was confirmed in both cases.     

Mitochondrial genomes from modern horses reveal the major haplogroups that underwent domestication

Archaeological and genetic evidence concerning the time and mode of wild horse (Equus ferus) domestication is still debated. High levels of genetic diversity in horse mtDNA have been detected when analyzing the control region; recurrent mutations, however, tend to blur the structure of the phylogenetic tree. Here, we brought the horse mtDNA phylogeny to the highest level of molecular resolution by analyzing 83 mitochondrial genomes from modern horses across Asia, Europe, the Middle East, and the Americas. Our data reveal 18 major haplogroups (A-R) with radiation times that are mostly confined to the Neolithic and later periods and place the root of the phylogeny corresponding to the Ancestral Mare Mitogenome at ~130-160 thousand years ago. All haplogroups were detected in modern horses from Asia, but F was only found in E. przewalskii--the only remaining wild horse. Therefore, a wide range of matrilineal lineages from the extinct E. ferus underwent domestication in the Eurasian steppes during the Eneolithic period and were transmitted to modern E. caballus breeds. Importantly, now that the major horse haplogroups have been defined, each with diagnostic mutational motifs (in both the coding and control regions), these haplotypes could be easily used to (i) classify well-preserved ancient remains, (ii) (re)assess the haplogroup variation of modern breeds, including Thoroughbreds, and (iii) evaluate the possible role of mtDNA backgrounds in racehorse performance.     

Immunoglobulin and complement depositions in the liver of chronic hepatitis patients

BACKGROUND/AIMS: Liver biopsy is a cornerstone in the management of chronic hepatitis patients. In biopsy, liver cell damage as well as severity of inflammatory cell infiltration in the parenchyma and portal tracts are evaluated. There are some other inflammatory markers such as complements (C) and immunoglobulins (Ig), which are involved in the pathogenesis of inflammation. This study was carried out to investigate the status of Ig and C depositions in the liver of chronic hepatitis cases. METHODOLOGY: Two biopsy samples were taken from patients who were scheduled for liver biopsy for chronic hepatitis. The acetone fixed sections were incubated with fluorescin-conjugated anti human IgG, IgA, IgM, C3 and C4. Ten samples of non-hepatitis control cases were provided during elective cholecystectomy. RESULTS: Deposition of IgG, IgM, and Cs were seen in the parenchyma in HBV, HCV and non viral hepatitis cases. The parenchyma of control liver did not show any deposition of IgG, IgM, and Cs. IgA was found in the parenchyma of 3 control cases. C3 deposition in the parenchyma had significant association with enzyme rising in HCV (p=0.001) and non viral groups (p=0.004). C4 deposition in the parenchyma was also associated with enzyme rising in HCV cases (p=0.01). There was an association between ALT elevations with the presence of IgM in the parenchyma in HBV (p=0.01) and HCV (p=0.03) groups. Mantel-Haenszel chi2 test (for evaluation of the effects of stage and grade) confirmed that the depositions of C3 and C4 in HCV and C3 in nonviral hepatitis have positive association with enzyme rising. CONCLUSIONS: Presence of IgM, IgG, C3, and C4 in the liver parenchyma is abnormal and may be helpful in histological evaluation in chronic hepatitis. Parenchymal (but not portal) depositions of C3 and C4 in HCV and non-viral hepatitis cases show close association with elevation of liver enzymes.