Imbalance between Angiotensin II - Angiotensin (1-7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension

AimDiabetes is associated with Renin-angiotensin-aldosterone-system (RAAS) activation. Protective role of Angiotensin (1-7) has been recently identified. The study aims to identify associations between imbalance in RAAS components with vascular endothelial dysfunction and inflammation in diabetics with newly diagnosed hypertension.MethodsBrachial Flow-mediated-dilation (FMD), Carotid Intima-media-thickness (CIMT), pulse-wave-velocity (PWV), Serum E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), high-sensitivity C-Reactive Protein (hsCRP), Interleukin-10 (IL-10), Renin, AngiotensinII, Angiotensin-Converting-Enzyme 2 (ACE2) and Angiotensin1-7 were measured in 60 diabetic patients with newly diagnosed hypertension. Patients with AngiotensinII/Angiotensin1-7 ratio <1 were classified as Favourable-Axis (FA) group (n = 22) and those with ratio >1 were classified as Unfavourable-Axis (UA) group (n = 38).ResultshsCRP was higher [9.52 (4.64–16.19) vs 3.62 (1.77–13.09) (mg/l), p = 0.04], IL-10 was lower [2.26 (1.34–12.05) vs 10.98 (4.44–17.78) (pg/ml),p = 0.006], %FMD was lower [(5.51 ± 2.97) vs (7.66 ± 3.38) (%), p = 0.01] and CIMT was higher in UA compared to FA group [0.7 (0.55–0.79) vs 0.51 (0.49–0.65) (mm), p = 0.001]. Renin correlated positively with pressure, PWV, E-selectin and VCAM-1, opposing associations were obtained for Angiotensin1-7 and ACE2.ConclusionImbalance between AngiotensinII – Angiotensin1-7 is associated with increased inflammation and vascular dysfunction in diabetics and can contribute to development of hypertension in these patients.     

Late presentation of fractures of the lateral condyle of the humerus in children

Background:

The current controversy regarding the management of fractures of the lateral condyle of the humerus presenting between 3 to 12 weeks prompted us to evaluate our results of open reduction and internal fixation of such fractures.

Patients and Methods:

Twenty-one patients operated between March 1995 and February 2001 qualified for this study. Five patients presented between 3–4 weeks, nine between 5–8 weeks and seven between 9–12 weeks post injury. Ten fractures were classified as stage II and eleven as stage III (Jacob et al. criteria). The mean age was 8 years (range: 4–14 years). All patients underwent surgery (open reduction and internal fixation with K-wires/screw, with or without bone grafting). The results were assessed by the modified criteria of Agarwal et al. after an average follow-up of 2.3 years.

Results:

Excellent to good results were observed in all the five patients presenting at 3–4 weeks post injury. In the patients presenting at 5–8 weeks, the results were excellent in one, good in four, fair in three, and poor in one patient. The fracture united in all cases; however, malunion was observed in four patients. The fractures that were operated at 9–12 weeks showed good results in one case, fair result in three cases, and poor result in three cases. Avascular necrosis of the lateral condyle in one patient, premature fusion in two patients, pin tract infection in three patients, and gross restriction of elbow movements in three patients were the major complications in this group. Accurate reduction was difficult as a result of new bone formation and remodeling at the fracture surfaces. Multiple incisions over the common extensor aponeurosis and bone graft supplementation were helpful for achieving acceptable reduction.

Conclusion:

Open reduction and internal fixation is recommended in all cases of displaced fractures of the lateral condyle of the humerus presenting at up to 12 weeks post injury. However, the results become poorer with increase in duration after injury and the grade of displacement. To avoid complications it is important to carry out careful dissection of the soft tissue attachments and to mobilize the fragment without the use of force.     

Long-Term Durability of Transcatheter Aortic Valve Prostheses

Background

Very little is known about long-term valve durability after transcatheter aortic valve replacement (TAVR).

The burden of prostate cancer in Trinidad and Tobago: one of the highest mortality rates in the world

Purpose

In Trinidad and Tobago (TT), prostate cancer (CaP) is the most commonly diagnosed malignancy and the leading cause of cancer deaths among men. TT currently has one of the highest CaP mortality rates in the world.

Methods

6,064 incident and 3,704 mortality cases of CaP occurring in TT from January 1995 to 31 December 2009 reported to the Dr. Elizabeth Quamina Cancer population-based cancer registry for TT, were analyzed to examine CaP survival, incidence, and mortality rates and trends by ancestry and geography.

Results

The age-standardized CaP incidence and mortality rates (per 100,000) based on the 1960 world-standardized in 2009 were 64.2 and 47.1 per 100,000. The mortality rate in TT increased between 1995 (37.9 per 100,000) and 2009 (79.4 per 100,000), while the rate in the US decreased from 37.3 per 100,000 to 22.1 per 100,000 over the same period. Fewer African ancestry patients received treatment relative to those of Indian and mixed ancestry (45.7%, 60.3%, and 60.9%, respectively).

Conclusions

Notwithstanding the limitations surrounding data quality, our findings highlight the increasing burden of CaP in TT and the need for improved surveillance and standard of care. Our findings highlight the need for optimized models to project cancer rates in developing countries like TT. This study also provides the rationale for targeted screening and optimized treatment for CaP to ameliorate the rates we report.

     

Immune response to GOR,a marker for non-A,non-B hepatitis and its correlation with hepatitis C virus infection

Recently, identification and molecular cloning of a host cellular gene designated GOR from chimpanzees experimentally infected with non-A, non-B hepatitis (NANBH) agent was reported. It was further demonstrated that there is a close association between the immune response to an antigenic peptide of GOR (GOR2) and NANBH. In order to define the specificity of the immune response, in the present study we have identified an additional epitope in the GOR gene sequence, upstream from GOR2, and studied its correlation with the immune response to hepatitis C virus (HCV) in NANBH patients. An enzymelinked immunoassay (EIA) was developed which utilizes synthetic peptides designated spGOR346 and spGOR2 as the serological target for the detection of anti-GOR antibodies in patient serum samples from various hepatic and non-hepatic disease categories. GOR peptides identified 80-90% of the NANBH samples that were positive for HCV C100-3 and about 70% of the NANBH samples that were positive by Abbott prototype second-generation HCV antibody assay. Among a normal donor population(s), only 2-3% of the samples were positive for antibodies to GOR sequences, whereas from the patient categories unrelated to viral hepatitis as well as various nonhepatic diseases, the immune response to both GOR peptides was closely associated with the presence of antibodies to HCV. The data indicate that antibodies to GOR is a marker associated with NANBH.     

Pediatric renal transplant practices in India

Limited access to tertiary‐level health care, limited trained pediatric nephrologists and transplant physicians, lack of facilities for dialysis, lack of an effective deceased donor program, non‐affordability, and non‐adherence to immunosuppressant drugs poses a major challenge to universal availability of pediatric transplantation in developing countries. We present the results of a survey which, to the best of our knowledge, is the first such published attempt at understanding the current state of pediatric renal transplantation in India. A designed questionnaire formulated by a group of pediatric nephrologists with the aim of understanding the current practice of pediatric renal transplantation was circulated to all adult and pediatric nephrologists of the country. Of 26 adult nephrologists who responded, 16 (61.5%) were involved in pediatric transplantation, and 10 of 15 (66.6%) pediatric nephrologists were involved in pediatric transplantation. Most of the centers doing transplants were private/trust institution with only three government institutions undertaking it. Induction therapy was varied among pediatric and adult nephrologists. There were only a few centers (n=5) in the country routinely doing >5 transplants per year. Preemptive transplants and protocol biopsies were a rarity. The results demonstrate lower incidence of undertaking pediatric transplants in children below 6 years, paucity of active cadaveric programs and lack of availability of trained pediatric nephrologists and staff. In contrast to these dissimilarities, the immunosuppressant use seems to be quite similar to Western registry data with majority favoring induction agent and triple immunosuppressant (steroid, mycophenolate mofetil and tacrolimus) for maintenance. The survey also identifies major concerns in availability of this service to all regions of India as well as to all economic segments.     

N‐acetyl cysteine‐mediated effective attenuation of methoxychlor‐induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary

Methoxychlor (MXC), an organochloride insecticide, is a potent toxicant‐targeting female reproductive system and known to cause follicular atresia by inducing apoptosis within granulosa cells. Oxidative stress plays a pivotal role in apoptosis; thus, this study focuses on the ameliorative action of N‐acetyl cysteine (NAC) on MXC‐induced oxidative stress and apoptosis within granulosa cell of caprine ovary. Classic histology, fluorescence assay, and biochemical parameters were employed to evaluate the effect of varied concentration of NAC (1, 5, and 10 mM) on granulosa cell apoptosis after 24, 48, and 72 h exposure duration. Histomorphological studies revealed that NAC diminished the incidence of apoptotic attributes like condensed or marginated chromatin, pyknosis, crescent‐shaped nucleus, empty cell spaces, and degenerated cellular structure along with the presence of cytoplasmic processes within granulosa cells in dose‐ and time‐dependent manner. NAC significantly downregulated the percentage of MXC‐induced granulosa cell apoptosis within healthy ovarian follicle with its increasing dose, maximum at 10 mM concentration. It also significantly (p < 0.05) upregulated the activity of antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione‐s‐transferase, along with ferric reducing antioxidant power further declining lipid peroxidation in the MXC‐treated caprine ovary. The results revealed a negative correlation between apoptosis frequency and antioxidant enzymes’ activity (r _CAT = ?0.67, r _SOD = ?0.56, r _GST = ?0.31; p < 0.05) while a positive correlation was observed with lipid peroxidation (r = 0.63; p < 0.05) after NAC supplementation. Thus, NAC supplementation reduces the MXC‐generated oxidative stress that perhaps declines the ROS generating signal transduction pathway of apoptosis, thereby preventing MXC‐induced granulosa cell apoptosis and follicular atresia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 156–166, 2017.