FK506-binding protein localizations in human penile innervation

OBJECTIVE

To determine if FK506‐binding proteins (FKBPs) are localized to the autonomic nerve supply of the human penis because FK506 (an immunosuppressant drug) has been linked to enhanced nerve regeneration after nerve injury and neurodegenerative diseases by binding to FKBPs, a select group of immunophilins.

MATERIALS AND METHODS

Human lower genitourinary tract specimens were obtained and embedded in paraffin wax. The tissue was sectioned (10 µm) and processed for immunohistochemistry using antibodies for FKBPs 12, 38, 52, 65, 135 and neuronal nitric oxide synthase (nNOS). To confirm specificity of the antibody, we processed some tissue in the absence of primary antibody, with mouse or rabbit IgG, and with a blocking peptide for FKBP12.

RESULTS

In the pelvis, immunoreactivity for all the FKBPs and nNOS was localized to the periprostatic ganglia although FKBP12 was the only FKBP localized to nerve bundles in this location. In penile tissue, immunoreactivity for all five FKBPs and nNOS was localized to nerves, although immunoreactivity for FKBP38 was minimal. The FKBPs were also evident in epithelial, endothelial and smooth muscle cells of the prostate and penis. Negative controls did not produce staining.

CONCLUSIONS

Identification and localization of immunophilins to nerves coursing in prostate and penile tissue suggest a likely molecular basis to apply immunophilin ligand therapy to protect or regenerate cavernosal nerves. Our findings support the hypothesis that immunosuppressant drugs such as FK506, working via specific receptor mechanisms, are potentially useful to sustain erectile function in men after radical prostatectomy.     

Vitamin E and <Emphasis Type="SmallCaps">l</Emphasis>-carnitine,separately or in combination,in the prevention of radiation-induced brain and retinal damages

Our aim was to determine the effects of vitamin E and l-carnitine supplementation, individually or in combination, on radiation-induced brain and retinal damages in a rat model. Group 1 received no treatment (control arm). Group 2 received a total dose of 15 Gy external radiotherapy (RT) to whole brain by Cobalt-60 teletherapy machine. Groups 3, 4, and 5 received irradiation plus 40 kg⁻¹ day⁻¹ Vitamin E or 200 mg kg⁻¹day⁻¹ l-carnitine alone or in combination. Brain and retinal damages were histopathologically evaluated by two independent pathologists. Antioxidant enzyme levels were also measured. Radiation significantly increased brain and retinal damages. A significant increase in malondialdehyde levels as well as a decrease in superoxide dismutase and catalase enzymes in brain was found in group 2. Separate administration of Vitamin E+RT and l-carnitine+RT significantly reduced the severity of brain and retinal damages and decreased the malondialdehyde levels and increased the activity of superoxide dismutase and catalase enzymes in the brain. The findings of current study support the antioxidant and radioprotective roles of vitamin E and l-carnitine. However, the combined use of Vitamin E and l-carnitine plus irradiation interestingly did not exhibit an additive radioprotective effect.     

Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model

Introduction

Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models.

Objective

We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury.

Methods

Thirty rats were divided into three groups as sham (n=10), control (n=10) and thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy.

Results

Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI). Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons).

Conclusion

Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model.     

Single-Nucleotide Polymorphisms in IL23R-IL12RB2 (rs1495965) Are Highly Prevalent in Patients with Behcet’s Uveitis and Vary Between Populations

Purpose: To test the frequency of single-nucleotide polymorphisms in the IL-10, IL23R-IL12RB2 genes in patients with Behcet’s uveitis.

Methods: Blood samples were collected from 89 Israeli and Turkish patients, and from healthy control subjects of different origins. Genomic DNA was extracted from peripheral blood leukocytes and genotyped.

Results: The risk allele, A, in rs1800871, of IL-10 gene was highly prevalent in Behcet’s uveitis and healthy control samples alike; highest among the Turkish groups. Prevalence of G allele, in rs1495965, in the IL23R-IL12RB2 gene was high in Behcet’s uveitis patients, and among healthy Turkish and Israelis of Middle Eastern origin, while lower among the other Israeli control group (77.9%, 78.9%, 27.8%, respectively, P < 0.001).

Conclusion: Our findings highlight the differences between populations and may account for the increased prevalence of the disease among Turkish and Israelis of Middle Eastern origin. Further studies are required to map other healthy and affected populations.     

New era of pediatric ventricular assist devices: Let us go to school

As there is still a shortage of pediatric donor hearts, several techniques have been used to assist pediatric patients to survive until transplantation. VADs provide long‐term support and ability of mobilization for children before a suitable heart becomes available. Several devices such as paracorporeal pumps have been used for this purpose, with acceptable morbidity and mortality rates. However, discharge is not possible, as there is no mobile drive unit for these small‐sized pumps. The possible negative psychosocial impact of long‐term hospitalization, away from home and school, may cause some adjustment problems in the future. In this case series, three pediatric patients that underwent intracorporeal LVAD implantation and returned to school are presented to share clinical experience and also to attract attention to the potential social and psychiatric implications.     

Effects of Hyperbaric Oxygen and Preconditioning on Wound Healing in Colonic Anastomoses

Aim: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. Materials and Methods: A total of 21 Sprague–Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. Results: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. Conclusions: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.     

The comparison of dexmedetomidine and midazolam used for sedation of patients during upper endoscopy: A prospective, randomized study.

The aim of the present prospective, randomized study was to investigate and compare the safety and efficacy of dexmedetomidine versus midazolam in providing sedation for gastroscopy. A total of 50 adult patients (25 patients receiving dexmedetomidine and 25 patients receiving midazolam), 18 to 60 years of age, and rated I and II on the American Society of Anesthesiologists physical status classification system were included. A brief questionnaire was used to collect demographic data; patients were asked to rate anxiety, satisfaction with care to date and expected discomfort on a visual analogue scale. The following parameters were measured continuously and recorded every minute: heart rate, mean arterial pressure, hemoglobin oxygen saturation and respiratory rate. The two groups were similar with regard to age, body mass index, sex, education, duration of endoscopy, and ethanol or tobacco use. After the procedure, full recovery time, mean arterial pressure, heart rate, respiratory rate and hemoglobin oxygen saturation levels were similar in both groups. Both groups also had low levels of perceived procedural gagging, discomfort and anxiety scores (P > 0.05), and high satisfaction levels (90.1+/-3.0 for dexmedetomidine versus 84.9+/-4.5 for midazolam; P > 0.05). Retching and endoscopist satisfaction were significantly different in patients receiving dexmedetomidine versus those receiving midazolam (88.8+/-6.5 versus 73.5+/-16.4, P < 0.05; and 20.6+/-4.4 versus 45.2+/-6.0; P < 0.001). In the midazolam group, the number of patients who had adverse effects was higher than the dexmedetomidine group (P < 0.05). As a result, dexmedetomidine performed as effectively and safely as midazolam when used as a sedative in upper gastroscopy; it was superior to midazolam with regard to retching, rate of side effects and endoscopist satisfaction. It was concluded that dexmedetomidine may be a good alternative to midazolam to sedate patients for upper endoscopy.     

Short‐Term Outcomes of Patent Ductus Arteriosus Closure With New Occlutech® Duct Occluder: A Multicenter Study

Aim

Over the past 2 decades, transcatheter occlusion of patent ductus arteriosus (PDA) with coils and the duct occluders evolved to be the procedure of choice. A new device, the Occlutech PDA® occluder (ODO) device has been designed. Herein, we aimed to evaluate the characteristics and short‐term results of patients who underwent transcatheter closure of PDA using the ODO.

Methods

We reviewed the clinical records of 60 patients from different centers in Turkey between December 2013 and January 2016. The medical records were reviewed for demographic characteristics and echocardiographic findings. Device size was selected on the narrowest diameter of PDA.

Results

The median patient age was 2.5 years (6 months–35 years), and median PDA diameter was 2.5 mm (1.2–11 mm). Fifty‐eight of 60 patients (96.6%) had successful ODO implantation. The occlusion rates were 37/58 (63.7%) at the end of the procedure, 51/58 (87.9%) at 24–48 hours post‐procedure, and 57/58 (98.2%) on echocardiography at a median follow‐up of 7.6 months.

Conclusion

Our results indicate that transcatheter closure of PDA using the ODO is effective. Larger studies and longer follow‐up are required to assess whether its shape and longer length make it superior to other duct occluders in large, tubular, or window‐type ducts. (J Interven Cardiol 2016;29:325–331)