Serum-free liquid marrow culture in patients with acute lymphoblastic leukaemia: a potential application to purge marrow for autologous transplantation

We have previously established a serum-free (SF) culture medium, which supports normal haemopoietic progenitor cell growth for at least 4 weeks as does conventional serum dependent (SD) medium. In the present study, we investigated the efficacy of such a defined SF liquid medium which sustained in vitro residual normal haemopoietic proliferation of marrow derived from ALL patients and which was detrimental for the leukaemic population. Evidence for a potential selective effect of SF culture was obtained by a leukaemic progenitor cell assay (ALL-CFU) and the detection of the bcr/abl translocation by polymerase chain reaction (PCR). In 13 experiments including 12 patients, morphological blast cells and ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. Likewise, in 5/5 experiments in SD and 2/5 experiments in SF conditions, leukaemic cells expressing the bcr/abl fusion gene disappeared within 3-4 weeks. In contrast, the absolute numbers of supernatant cells harvested weekly from SF and SD cultures were similar. No difference in CFU-GM production was detected for the two culture systems. Erythropoiesis in SF medium exhibited a slower decline than that found in SD. These results indicate that liquid marrow culture may selectively deplete leukaemic lymphoblastic cells and enable repopulation by residual normal haemopoietic cells. This technique may be useful to purge leukaemic cells for clinical autologous bone marrow transplantation in patients with ALL.     

A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.     

Effect of Photoactivated Disinfection on Bond Strength of Root Canal Filling

IntroductionThe aim of this in vitro study was to assess and compare the effect of photoactivated disinfection (PAD) on the bond strength of root canal sealers to human root canal dentin using the push-out test.MethodsFifteen extracted human mandibular premolar teeth with single and straight roots were used. After the clinical crowns were removed from the cementoenamel junction, root canals were prepared with the ProTaper (Dentsply Maillefer, Ballaigues, Switzerland) rotary system to the size of the F3 file. The smear layer of the roots was removed using 17% EDTA followed by 5.25% sodium hypochlorite (NaOCl) and distillate water. The roots were then randomly divided into 3 groups (n = 5) according to the final irrigation regimen. In group 1, PAD (FotoSan; CMS Dental, Copenhagen, Denmark) was applied to the root canals and light cured for 20 seconds. Group 2 was finally irrigated with a 2% solution of chlorhexidine gluconate, and group 3 served as the control group (NaOCl + EDTA). All the canals were then obturated with the lateral condensation technique using gutta-percha and AH Plus sealer (Dentsply Maillefer) sealer. One-millimeter-thick horizontal sections from the coronal and midthirds of each root (n: 5 × 4 = 20) were sliced for the push-out bond strength measurement. The data were converted to megapascals and statistically analyzed using 1-way analysis of variance and the post hoc Tukey test.ResultsThere was no significant difference among the bond strength of PAD, chlorhexidine gluconate, and NaOCl (P > .05).ConclusionsWe conclude that PAD does not adversely affect the bond strength of the AH Plus sealer to root canal dentin and that it can be used for the final disinfection of root canals.     

In Vitro Fracture Resistance of Endodontically Treated Roots Filled with a Bonded Filling Material or Different Types of Posts

AimThis study aimed to compare the fracture resistance of roots filled with a bonded material, fiber posts, or titanium post systems.MethodsCanals in the first group were filled with AH Plus and gutta-percha cones, and roots in the second group were filled with Epiphany sealer and Resilon cones. The root fillings (60 roots) were removed up to 4 mm from the canal apex to obtain 10-mm-deep post spaces, and posts were cemented. The groups were as follows: AH Plus control group, Epiphany control group, AH Plus fiber post group, AH Plus titanium post group, Epiphany fiber post group, and Epiphany titanium post group. Fracture tests were performed by using an Instron testing machine. The force was applied at a 45° axial angle with a constant speed of 1 mm/min. For each sample, the force at which fracture occurred was recorded in units of newtons. Statistical analysis was carried out by using analysis of variance test.ResultsThere was no statistically significant difference between all groups (P > .05).ConclusionsTitanium posts, fiber posts, and Epiphany root canal filling systems were found to have no reinforcing effect on endodontically treated roots.     

Mesangial proliferative glomerulonephritis in familial Mediterranean fever patient with E148Q mutation: the first case report

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease characterized by recurrent attacks of fever, usually accompanied by sterile polyserositis. Although amyloidosis is the most common renal involvement, non-amyloid renal lesions, such as glomerulonephritis, have been described in patients with FMF. In this report, we present the first case of an FMF patient with heterozygous mutation of E148Q, mesangial proliferative glomerulonephritis, and no amyloidosis. While the association of mutation E148Q with renal involvement is still obscure, colchicine treatment is useful in mesangial proliferative glomerulonephritis with FMF.     

Effect of Dexmedetomidine on Ischemia-Reperfusion Injury in Rat Kidney: A Histopathologic Study

Ischemia-reperfusion (I-R) injury remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine on histologic alterations induced by renal I-R in rats. In the present study, thirty male Sprague-Dawley rats weighing 200–220 g were randomly assigned into three groups: the sham-control group (group 1, n?=?10), the R/untreated group (group 2, n?=?10), and the I-R/dexmedetomidine-treated group (group 3, n?=?10). For group one, we performed a sham operation. The abdomen was dissected, the right kidney was harvested, and then the left renal pedicle exposed. Renal clamping was not applied. For group 2, rats underwent left renal ischemia for 60 minutes followed by reperfusion for 45 minutes. For group 3, the same surgical procedure as in group 2 was performed, and dexmedetomidine (100 μg/kg, intraperitoneal) was administrated at the starting time of reperfusion. The rats were sacrificed after reperfusion, and the kidney tissue was harvested. The histopathological score in the kidney of the I-R/dexmedetomidine-treated group rats was significantly lower than that of I-R/untreated group rats. This score in I-R/untreated group rats was higher than the other two groups, which was statistically significant. In the I-R/untreated group rats, kidneys of untreated ischemia rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with dexmedetomidine shows normal glomeruli and slight edema of the tubular cells. These findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidney against renal injury.     

Influence of smoking on interleukin-1beta level, oxidant status and antioxidant status in gingival crevicular fluid from chronic periodontitis patients before and after periodontal treatment

Toker H, Akp?nar A, Ayd?n H, Poyraz O. Influence of smoking on interleukin‐1beta level, oxidant status and antioxidant status in gingival crevicular fluid from chronic periodontitis patients before and after periodontal treatment. J Periodont Res 2012; 47: 572–577. © 2012 John Wiley & Sons A/S Background and Objective: The aim of this study was to evaluate the impact of smoking on the relationship between interleukin‐1 (IL‐1β) and oxidation in patients with periodontitis and response to nonsurgical periodontal therapy. Material and Methods: Data were obtained from 30 patients with generalized chronic periodontitis (15 smokers and 15 nonsmokers) and from 10 periodontally healthy controls. IL‐1β level, total oxidant status (TOS) and total antioxidant status (TAS) were recorded in gingival crevicular fluid. Probing depth, clinical attachment level, gingival and plaque indices and bleeding on probing were also measured. The gingival crevicular fluid and clinical parameters were recorded at baseline and 6 wk after periodontal treatment. Results: The study showed statistically significant improvement of clinical parameters in both smokers and nonsmokers after periodontal treatment. Moreover, the baseline IL‐1β levels were significantly higher in smokers compared with nonsmokers (p < 0.05). After periodontal treatment, the IL‐1β levels were significantly reduced in both smokers and nonsmokers (p < 0.05). There were no significant differences in TOS and TAS between periodontitis patients and healthy controls at baseline and 6 wk after periodontal treatment. The level of IL‐1β in gingival crevicular fluid was positively correlated with TOS in both smokers and nonsmokers. Conclusions: Periodontal treatment improved the clinical parameters in both smokers and nonsmokers. The results confirm that periodontal therapy has an effect on IL‐1β levels in gingival crevicular fluid, but not on TOS and TAS.     

Levels of gingival tissue platelet activating factor after conventional and regenerative periodontal surgery

The hypothesis, a relationship between gingival tissue platelet activating factor (PAF) levels and healing after periodontal surgery, was tested by measuring PAF levels in gingival tissues collected from sites that had undergone flap surgery and guided tissue regeneration (GTR) or flap surgery alone. Using a split-mouth design, 20 intrabony defects were randomly assigned to treatment with flap surgery and GTR (group 1) or with flap surgery alone (group 2). Gingival tissue samples were obtained at surgery (baseline) and at 6-month follow-up evaluation visit. One half of each sample was used for analysis of PAF levels by high-performance liquid chromatography, and the other half of the sample was used for histomorphometric analysis that included measurements of number and diameter of blood vessels. PAF levels and diameter of blood vessels were significantly decreased (p < 0.01), and the number of blood vessels was significantly increased (p < 0.05) in both groups after 6 months compared to the baseline values. Postoperative number of blood vessels were significantly higher in group 1 (p < 0.05), whereas there was no significant difference in postoperative PAF levels between the two groups (p > 0.05). Based on the reported results, it is suggested that a decrease in gingival PAF levels might be found after conventional and regenerative periodontal surgery.     

Comparison of the safety and efficacy of the on-demand use of sertraline,dapoxetine, and daily use of sertraline in the treatment of patients with lifelong premature ejaculation: A prospective randomised study

This study compared the safety and efficacy of the on-demand (OD) use of sertraline (50 mg), sertraline (100 mg) and dapoxetine (30 mg), and the daily use of sertraline (50 mg) in the treatment of patients with premature ejaculation (PE). This prospective randomised study involved 120 lifelong PE patients (intravaginal ejaculatory latency time [IELT]: <1 min; Arabic Index of Premature Ejaculation [AIPE] score: < 30) without secondary causes of PE, identified between March 2018 and May 2020. Patients were divided into 4 groups (30 patients per group) and treated for 8 weeks. Assessments were conducted using the AIPE form as a diagnostic tool. Sertraline (50 mg, daily; 196.7 ± 115.5 s) and sertraline (100 mg, OD; 173.3 ± 97.0 s) had similar IELT and AIPE scores. The latter groups had better results in comparison with sertraline (50 mg, OD; 100.5 ± 54.4 s) and dapoxetine (93.7 ± 53.5 s; p < 0.01). Sertraline (100 mg, OD) had a similar efficacy to that of sertraline (50 mg, daily) and was more effective than sertraline (50 mg, OD) and dapoxetine (30 mg, OD). Sertraline (100 mg, OD) can be considered in the treatment of lifelong PE treatment, having tolerable side effects.