Serum Zinc and Copper Levels in Ischemic Cardiomyopathy

Changes in the copper (Cu) and zinc (Zn) concentrations have been reported previously in ischemic cardiomyopathy (ISCMP). Due to controversial results, the aims of this study were to compare levels of Cu, Zn, and Zn/Cu ratio of ISCMP patients with healthy volunteers and also to investigate the possible relationship between trace elements status in ISCMP patients with the severity of clinical disease based on the New York Heart Association (NYHA) classification. The subjects of this study consisted of 30 ISCMP and 27 healthy volunteers. ISCMP was diagnosed with a history of previous myocardial infarction and also coronary artery disease was confirmed by coronary angiography. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with the SPSS 10 software using independent sample t test for comparing the levels of Cu and Zn between ISCMP and normal subjects. The mean Cu level of the ISCMP group (1.54 ± 0.52 mg/L) was significantly more than the Cu levels of the healthy volunteers (1.31 ± 0.24 mg/L; p = 0.048). The mean Zn levels of the ISCMP and healthy volunteers were 1.05 ± 0.28 and 1.12 ± 0.42, respectively, without any significant difference between groups. There was a trend for higher Cu level, lower Zn level, and lower Zn/Cu ratio in NYHA III patients in comparison with NYHA II group. Considering the results of this study, Cu may have a role in the development of ISCMP. Interventions such as administration of Cu chelators to relieve the symptoms or to decrease the progression of ISCMP is needed to be examined in large clinical trials. In this study, the Zn level of ISCMP patients was not significantly different in comparison with the healthy volunteers.     

Isolation of Bacteria Able to Metabolize High Concentrations of Formaldehyde

Summary Nineteen bacterial strains able to degrade and metabolize formaldehyde as a sole carbon source were isolated from soil and wastewater of a formaldehyde production factory. The samples were cultured in complex and mineral salts media containing 370 mg formaldehyde/l. The bacterial strains were identified to be Pseudomonas pseudoalcaligenes, P. aeruginosa, P. testosteroni, P. putida, and Methylobacterium extorquens. After adaptation of these microorganisms to high concentrations of formaldehyde; two isolated strains of M. extorquens (strains ESS and PSS) and four strains of P. pseudoalcaligenes (strains LSW, SSW, NSW and OSS) degraded 1850 mg formaldehyde/l, where as P. pseudoalcaligenes strain OSS completely consumed 3700 mg of formaldehyde/l after 24 h and degraded 70% of 5920 mg of formaldehyde/l after 72 h.     

Intravascular pressure and diameter profile of the utero-ovarian resistance artery network: estrous cycle-dependent modulation of resistance artery tone

Blood flow to the ovary varies dramatically in both magnitude and distribution throughout the estrous cycle to meet the hormonal and metabolic demands of the ovarian parenchyma as it cyclically develops and regresses. Several vascular components appear to be critical to vascular regulation of the ovary. As a first step in resolving the role of the resistance arteries and their paired veins in regulating ovarian blood flow and transvascular exchange, we characterized the architecture and intravascular pressure profile of the utero-ovarian resistance artery network in an in vivo preparation of the ovary of the anesthetized Golden hamster. We also investigated estrous cycle-dependent changes in resistance artery tone. The right ovary and the cranial aspect of the uterus in 26 female hamsters were exposed for microcirculatory observations. Estrous-cycle phase was determined in each animal before experimentation. The utero-ovarian vascular architecture was determined and resistance artery diameters were measured in each animal by video microscopy. Servo-null intravascular pressure measurements were made throughout the uteroovarian arterial network in 11 of the animals. Architectural data showed a complex anastomotic network jointly supplying the uterus and ovary. Resistance arteries showed a high degree of coiling and close apposition to veins, maximizing countercurrent-exchange capabilities. Arterial pressure dropped below 60% of systemic arterial pressure before the arteries entered the ovary. Both the ovarian artery and the uterine artery, which jointly feed the ovary, showed cycle day-dependent changes in diameter. Arterial diameters were smallest on the day following ovulation, during the brief luteal phase of the hamster. The data show that resistance arteries comprise a critical part of a complex network designed for intimate local communication and control and suggest that these arteries may play an important role in regulating ovarian blood flow in an estrous cycle-specific manner.     

KRAS mutation and abnormal expression of Cripto-1 as two potential candidate biomarkers for detection of colorectal cancer development

Colorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto-1 (CR-1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty-five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR-1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR-1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR-1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR-1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development.     

Correction: Neutralizing Antibody Response after Intramuscular Purified Vero Cell Rabies Vaccination (PVRV) in Iranian Patients with Specific Medical Conditions

Objective

Post exposure prophylaxis using one of the WHO-approved vaccines is the method of choice for preventing rabies. Abnormal immune function in patients with some specific medical conditions, such as pregnancy, chronic hepatitis B virus infection, different types of cancers like lymphoma, diabetes I and II, corticosteroid consumption by patients with rheumatoid arthritis and lupus erythematosus, could impair the immunologic response to various vaccines. The immune response to rabies vaccination has never been examined in patients with any of these described medical conditions. This study purposed to evaluate the neutralyzing antibody response after vaccination with purified Vero cell rabies vaccine (PVRV) according to the WHO-recommended Post–Exposure Prophylaxis (PEP) "ESSEN" regimen.

Methods

Thirty healthy volunteers and 50 volunteers with different medical conditions who were exposed to a suspected rabid animal in the 2nd or 3rd category of exposure received 5 doses of PVRV under the ESSEN protocol. Three blood samples were collected on days 0 (before the first dose), 14, and 35. The anti-rabies antibody titer was measured using the Rapid Fluorescent Foci Inhibition Test (RFFIT) and an ELISA Bio-Rad, Platelia, Rabies II kit.

Results

All subjects reached NAb titers above 0.5 IU/ml by day 14 after vaccination. On day 35 (1 week after receiving the last rabies vaccine), anti-rabies antibodies were in the protective level (>0.5 IU/ml) in both groups. There was no statistically significant difference in anti-rabies antibody response due to the type of exposure (category 2 or 3), and successful seroconversion was confirmed in both groups.

Conclusion

In conclusion, the ESSEN protocol using the PVRV vaccine is sufficient for rabies prophylaxis in patients with specific medical conditions.     

G2/M-checkpoint activation in fasciata1 rescues an aberrant S-phase checkpoint but causes genome instability

The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1^KO and ATR^KO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresses the phenotype of WEE1- or ATR-deficient Arabidopsis (Arabidopsis thaliana) plants. We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fas1 plants. Knocking out SOG1 in the fas1 wee1 background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint.     

MGRN1‐dependent pigment‐type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4

Mice lacking the E3 ubiquitin ligase mahogunin ring finger‐1 (MGRN1) have a pleiotropic phenotype that includes spongiform neurodegeneration, embryonic patterning defects, and dark fur due to a defect in pigment‐type switching. The only MGRN1 ubiquitination target identified to date is tumor susceptibility gene 101 (TSG101), a component of the endosomal trafficking machinery. Here, we show that MGRN1 also interacts with but does not ubiquitinate NEDD4, a HECT‐domain ubiquitin ligase involved in endosomal trafficking. Using transgenesis in mice, we demonstrate that pigment‐type switching likely requires MGRN1′s ubiquitin ligase activity but not its ability to bind TSG101 or NEDD4. This indicates that MGRN1‐dependent ubiquitination of an as‐yet unidentified target protein is required for agouti‐mediated melanocortin signaling.