Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study

OBJECTIVE: To study expressions of Notch receptor isoforms (Notch 1, 2, and 3) in normal and varicocele-induced rat testes to examine their possible functions in cell fate. DESIGN: Comparative and controlled study. SETTING: Animal Care and Operation Unit, Akdeniz University. ANIMAL(S): Wistar male rats for experimental and control groups. INTERVENTION(S): The control group underwent a sham operation (n = 6). The experimental groups underwent partial ligation of the renal vein to induce an experimental varicocele and then were killed 9 (n = 6), 11 (n = 6), and 13 (n = 6) weeks after the induction of varicocele. MAIN OUTCOME MEASURE(S): All tissues were fixed and routinely processed for paraffin embedding. Subsequent immunohistochemical studies were performed. RESULT(S): In the sham-operation rat testes, Leydig cells and elongated spermatids were immunopositive for Notch 1. Notch-2 expression was present in Leydig cells, spermatogonia, and primary spermatocytes. Notch-3 expression was limited to Leydig cells. Varicocele formation diminished the expression of both Notch-1 and Notch-2 receptors as the varicocele formation progressed over time. CONCLUSION(S): The present study suggests that Notch 1 is related to the maturation of spermatids. Notch 2 is related to both proliferation and maturation of spermatogenic cells, whereas Notch 3 seems to be related to Leydig cell functions. The decrease of both Notch-1 and Notch-2 expression depended on the degree of varicocele development over time, indicating a potential role in varicocele-associated testicular dysfunction.     

Intrathecal morphine: Effects on perioperative hemodynamics, postoperative analgesia, and stress response for total abdominal hysterectomy

Intrathecal opioids provide postoperative analgesia and hemodynamic stability by depressing the neuroendocrine response during the perioperative period. The effects of preoperative intrathecal morphine on perioperative hemodynamics, stress response, and postoperative analgesia were evaluated in patients undergoing abdominal hysterectomy with general anesthesia. A total of 24 patients were randomly assigned to the morphine group (n=12) or the control group (n=12). Patients in the morphine group were given intrathecal 5 μg/kg⁻¹ morphine before surgery. In all patients, general anesthesia was induced with 1 g/kg⁻¹ remifentanil, 2 mg/kg⁻¹ propofol, and 0.1 mg/kg⁻¹ vecuronium and was maintained with 1% to 2% sevoflurane—35% oxygen in N₂O and remifentanil infusion. All patients received intravenous morphine patient-controlled analgesia after surgery. Postoperative pain was evaluated by means of a visual analogue scale. Blood samples were taken at 4 time points before and up to 4 hours after the start of surgery for assessment of plasma epinephrine, norepinephrine, and glucose. Mean arterial pressure (MAP), heart rate (HR), and adverse effects were recorded. Intraoperative hemodynamics was similar in both groups, but postoperative HR and MAP values at 4 h, 8 h, 12 h, and 20 h were significantly lower in the morphine group (P < .05). Postoperative VAS scores, total morphine consumption, and plasma epinephrine, norepinephrine, and glucose levels were significantly lower in the morphine group than in the control group (P < .05). Preoperative intrathecal morphine enhanced the quality of postoperative analgesia, decreased morphine consumption, and depressed the systemic stress response in patients undergoing total abdominal hysterectomy with general anesthesia.     

Role of the poly(ADP-ribose)polymerase activity in vancomycin-induced renal injury

The aim of the present study was to investigate the role of poly(ADP-ribose)polymerase (PARP) activity in vancomycin (VCM)-induced renal injury and to determine whether 1,5-isoquinelinediol (ISO), a PARP inhibitor agent, could be offered as an alternative therapy in VCM-induced renal impairment. Rats were divided into four groups as follows: (i) control (Group 1); (ii) VCM-treated (Group 2); (iii) VCM plus ISO-treated (Group 3); and (iv) ISO-treated (Group 4). VCM (200 mg/kg, i.p., twice daily) was administered to Groups 2 and 3 for 7 days. ISO (3 mg/kg/day, i.p.) treatment was started 24 h before the first administration of VCM and continued for 8 days. After the 14th VCM injection, the animals were placed in metabolic cages to collect urine samples. All the rats were sacrificed by decapitation, blood samples were taken in tubes and kidneys were excised immediately. Blood urea nitrogen (BUN) and plasma creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG, a marker of renal tubular injury) were used as markers of VCM-induced renal injury in rats. Light microscopy was used to evaluate semi-quantitative analysis of the kidney sections. Poly(ADP-ribose) (PAR, the product of activated PARP) and PARP-1 expressions in renal tissues were demonstrated by immunohistochemistry and Western blot. VCM administration increased BUN levels from 8.07 ± 0.75 mg/dL to 53.87 ± 10.11 mg/dL. The plasma creatinine levels were 0.8 ± 0.04 mg/dL and 3.38 ± 0.51 mg/dL for the control and VCM-treated groups, respectively. Also, urinary excretion of NAG was increased after VCM injection. Besides, there was a significant dilatation of the renal tubules, eosinophilic casts within some tubules, desquamation and vacuolization of renal tubule epithelium, and interstitial tissue inflammation in VCM-treated rats. In VCM-treated rats, both PAR and PARP-1 expressions were increased in renal tubular cells. ISO treatment attenuated VCM-induced renal injury, as indicated by BUN and plasma creatinine levels, urinary NAG excretion, and renal histology. PARP inhibitor treatment also decreased PAR and PARP-1 protein expressions similar to that of controls. Herewith, the overactivation of the PARP pathway may have a role in VCM-induced renal impairment and pharmacological inhibition of this pathway might be an effective intervention to prevent VCM-induced acute renal injury.     

Demographic status and prevalence of intestinal parasitic infections in schoolchildren in Izmir, Turkey

Thirteen primary schools from nine areas were randomly selected in the shantytown and apartment districts in Izmir. Fecal specimens were evaluated with native-lugol, formalin-ethyl-acetate sedimentation and with trichrome staining for protozoa and helminths and with cellophane tape for Enterobius vermicularis. Of the study group, 33.4% had one or more parasites. The most common parasite was Blastocystis hominis (14.6%) followed by Enterobius vermicularis (10.1%) and Giardia intestinalis (7.8%). When parasitic distribution was evaluated in association with demographic features, a significant relation was found between the income level and parasitic infection prevalence. Multiple parasitic infections were more prevalent in crowded families (either extended or with many children). When parasitic infection prevalences in the 9-10 and 11-12 years of age groups were compared, the probability in the shantytown primary school group was significantly higher than in the apartment group (p<0.05).     

Changes after voice therapy in objective and subjective voice measurements of pediatric patients with vocal nodules

The aim of this study was to analyze the efficiency of the voice therapy in children with vocal nodules by using the acoustic analysis and subjective assessment. Thirty-nine patients with vocal fold nodules, aged between 7 and 14, were included in the study. Each subject had voice therapy led by an experienced voice therapist once a week. All diagnostic and follow-up workouts were performed before the voice therapy and after the third or the sixth month. Transoral and/or transnasal videostroboscopic examination and acoustic analysis were achieved using multi-dimensional voice program (MDVP) and subjective analysis with GRBAS scale. As for the perceptual assessment, the difference was significant for four parameters out of five. A significant improvement was found in the acoustic analysis parameters of jitter, shimmer, and noise-to-harmonic ratio. The voice therapy which was planned according to patients’ needs, age, compliance and response to therapy had positive effects on pediatric patients with vocal nodules. Acoustic analysis and GRBAS may be used successfully in the follow-up of pediatric vocal nodule treatment.     

Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction

The higher frequency of varicocele in men with infertility has drawn attention and resulted in increased research at the molecular level towards treatments. The aim of this study was to investigate the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptors in varicocele-induced testicular dysfunction in an experimental rat model. The rats were divided into three groups: control, sham and varicocele. Varicoceles in rats were induced by partial ligation of the left renal vein and left testes. The rats were analyzed 13 weeks after surgery. The degree of DNA fragmentation within cells in the testis was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay. Tubule degeneration was evaluated using the Johnsen score. The expression of TRAIL and its receptors was detected by immunohistochemical and Western blotting techniques. The apoptotic index, Johnsen score and the expression of TRAIL and TRAIL receptors were examined. The data are presented as the mean±s.d. and were analyzed using computer software. The Kruskal–Wallis and Dunn''s multiple comparison tests were used in the statistical analyses. The germ cell apoptotic index was increased in rats with varicoceles when compared with the sham and control groups (P=0.0031). The Johnsen score was significantly decreased in the varicocele group when compared with the sham and control groups (P<0.0001). Immunohistochemical and Western blotting analyses showed that after varicocele induction, the expression of TRAIL-R1 and TRAIL-R4 in germ cells was increased and the expression of TRAIL-R2 was decreased. There are no significant differences among the groups in terms of TRAIL and TRAIL-R3 receptor expression. The results of this study indicate that TRAIL and its receptors may have a potential role in the pathogenesis of varicocele-induced testicular dysfunction.