The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

Background

Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease.

Objective

To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats.

Method

SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study.

Results

In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days.

Conclusion

Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.     

The effects of verapamil and heparin co-administration on sperm parameters and oxidative stress in prevention of testicular torsion/detorsion damage in rats

In this research, the impacts of combined administration of verapamil and heparin on testicular torsion damage were examined. In this experimental study, 30 sexually mature male Wistar albino rats were divided into five equal groups haphazardly (n = 6): Group 1 was the sham group. In group 2, a 2-hr testicular torsion was induced, and thereafter, detorsion was done. Rats in group 3 and group 4 experienced an identical surgical procedure like group 2, but verapamil and heparin were administered in 0.3 mg/kg and 800 IU/kg doses respectively, and in group 5, a combination of verapamil and heparin were administered. Intraperitoneal drug injection in all treatment groups was done 30 min before testicular detorsion. Testicular torsion significantly changed sperm parameters, oxidative stress biomarkers and Cosentino's histological score compared to the sham group (p < .05). All treatment groups reduced testicular damage by decreasing oxidative stress and improving sperm parameters, but heparin and co-administration of verapamil and heparin were significantly better than verapamil injection alone. However, heparin injected group was more effective than other treatment groups (p < .05). Overall, an anticoagulant like heparin is more effective than a calcium channel blocker such as verapamil, and it is more likely to reduce testicular torsion injuries.     

Impact of silymarin on cadmium-induced apoptosis in human spermatozoa

Oxidative stress-induced apoptosis in spermatozoa may lead to male infertility. Environmental pollutants and heavy metals such as cadmium cause harmful effects on the reproductive system and sperm parameters through the induction of oxidative stress. Silymarin, as a potent antioxidant, is able to inhibit oxidative stress. This study was performed to investigate the protective effects of silymarin on cadmium-induced toxicity in human spermatozoa. Sperm samples were divided into the following five groups: (a) spermatozoa at 0 min, (b) spermatozoa in the control group, (c) spermatozoa treated with cadmium chloride (20 μM), (d) spermatozoa treated with silymarin (2 μM)+ cadmium chloride (20 μM) and (e) spermatozoa treated with silymarin (2 μM). Sperm parameters related to apoptosis, such as DNA fragmentation, nucleus diameter, mitochondrial membrane potential (MMP) and expression of caspase-3, were evaluated in all groups. After 180 min, spermatozoa treated with cadmium chloride showed a significant decrease in nucleus diameter and MMP but a significant increase in DNA fragmentation; however, caspase-3 expression remained unchanged. At this time point, silymarin in the silymarin + cadmium chloride group could significantly reverse the adverse effects of cadmium chloride on these parameters.Silymarn could partly compensate for the caspase-independent apoptosis in the spermatozoa. Therefore, oxidative stress could be a consequence for cadmium toxicity.     

Cutaneous basal cell carcinoma with endobronchial metastasis

Although basal cell carcinoma is a very common malignancy, metastasis from this tumour is extremely rare. For this reason, many plastic surgeons, dermatologists and physicians dealing with skin malignancies consider this as a locally invasive malignancy. We present a rare case of metastatic basal cell carcinoma manifested as a bronchial tumour. This case highlights the fact that despite basal cell carcinoma’s local invasive potential, the possibility of distant metastasis still exists and clinicians should therefore be cautious about interpreting extracutaneous symptoms. Chest physicians should always consider the possibility of this rare tumour in the lungs in patients with a history of large basal cell carcinomas in the head and neck region.     

Evaluation of humoral immune function in patients with bronchiectasis

Bronchiectasis is a chronic debilitating condition characterized by abnormal dilated thick-walled bronchi. To investigate humoral immune function in bronchiectatic patients, this study was performed. Forty patients with established diagnosis of bronchiectasis, who were referred from two tertiary care pulmonology centers in Tehran, were investigated in this study. Immunoglobulin isotypes concentrations and IgG-subclasses were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA) methods, respectively. All patients received unconjugated pneumococcal vaccine, and blood samples were taken before and 21 days after vaccination. Specific antibodies against whole pneumococcal antigens were measured using the ELISA method. Fifteen (37.5%) out of 40 patients were diagnosed to have defects in antibody mediated immunity including 5 (12.5%) patients with immunoglobulin class deficiency (2 with common variable immunodeficiency and 3 with IgA deficiency), 3 (7.5%) with IgG subclass deficiency and 7 (17.5%) patients had Specific antibody deficiency (SAD) against polysaccharide antigen despite normal levels of serum immunoglobulins and IgG subclasses. Our study along with several other studies confirmed that all patients with bronchiectasis should undergo thorough immunological evaluation in order to identify the presence of the underlying immunologic defect. This evaluation should include serum immunoglobulins, IgG subclasses concentrations and also determination of serum antibodies against pneumococcal antigens. Early diagnosis and appropriate treatment will prevent the subsequent complications and improve quality of life of affected individuals.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)