Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

Sanazole has been tested clinically as a hypoxic cell radiosensitizer. The aim of the present study was to investigate whether sanazole enhances apoptosis induced by hyperthermia at 44 degrees C for 20 min in human lymphoma U937 cells. Sanazole alone induced continuous increase in the intracellular superoxide generation in a time-dependent manner and transient increase in the peroxide formation, which further were enhanced at 1 hour after HT treatment. Moreover, when the cells were treated first with 10 mM sanazole for 40 min, exposed to HT at 44 degrees C for 20 min and the cells were further treated with the drug at 37 degrees C for 6 h, a significant enhancement of HT-induced apoptosis was evidenced by DNA fragmentation, morphological changes and phosphatidylserine externalization. Studying the apoptotic pathways involved in this enhancement, we found that loss of the mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, and activation of caspase-3 and caspase-8 was enhanced significantly in the U937 cells after the combined treatment. Moreover, this combination enhanced activation of Bid, and down regulation of Hsp70. In addition, an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)), and externalization of Fas were observed immediately after sanazole and HT treatment. Our data indicate that sanazole can enhance the hyperthermia induced-apoptosis through the Fas-caspase-8- and [Ca(2+)](i)-dependent apoptotic pathways. In addition, the down regulation of Hsp70 contributed to this enhancement.

AIM: The present study aimed to systematically assess current evidence on effects of locally delivered antibiotics during periodontal surgery compared to periodontal surgery alone on clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, recession depth (RD) changes, gingival index (GI), bleeding on probing (BOP), and plaque index (PI).

METHODOLOGY: MEDLINE-PubMed, Cochrane-CENTRAL and Scopus databases were searched up to April 2021 for randomized clinical trials (RCT), evaluating effects of locally delivered antibiotics during periodontal surgery. CAL gain served as primary, while PPD reduction, RD changes, GI and PI as secondary outcomes. The Cochrane Risk of Bias Tool was used to assess possible bias. Data were extracted, and meta-analysis was performed where appropriate.

RESULT: Screening of 2314 papers resulted in nine eligible studies. No adverse events were reported. Data on outcome variables were pooled and analyzed using generic inverse variance model and presented as weighted mean difference (WMD) and 95% confidence interval (95% CI). Statistically significant improvements in favor of antibiotics' delivery were observed in studies with follow-up of ≤6 months for CAL gain (WMD = 0.61 mm (95% CI [0.07, 1.14]; p = 0.03), PPD reduction (WMD = 0.41 mm (95% CI [0.02, 0.80]; p = 0.04)) and BOP (WMD = -28.47% (95% CI [-33.00, -23.94]); p < 0.001), while for GI improvements were notable for >6 to 12 months (WMD = -0.27 (95% CI [-0.49, -0.06]; p = 0.01)).

CONCLUSION: Within the current review's limitations, locally delivered antibiotics during surgical periodontal therapy results in post-surgical improvements for CAL, PPD, and BOP (≤6 months) with a longer-lasting GI improvement. Further randomized controlled trials are needed with true periodontal end-points to assess the ideal antibiotic agent, dosage, and delivery methods.

CLINICAL RELEVANCE: Local delivery of antibiotics during periodontal surgery improved clinical parameters for up to 6-month follow-up, with beneficial longer effects on gingival inflammation. Within the current study's limitation, the presented evidence could support the elective usage of locally delivered antibiotics during surgical periodontal therapy.

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This study aimed to assess the effect of varicocelectomy and/or mast cells (MCs) stabilizer on sperm DNA fragmentation in infertile men with varicocele (Vx). Overall, 120 infertile patients were randomized to three equal treatment arms; patients that underwent varicocelectomy, patients on 1 mg ketotifen twice daily for three months, and patients that underwent varicocelectomy followed with 1 mg ketotifen twice daily for three months. These patients were subjected to history taking, clinical examination, semen analysis, and estimation of sperm DNA fragmentation index (DFI). After 3 months, all investigated groups showed significant improvement regarding the mean total sperm count, sperm concentration, total sperm motility, and sperm normal forms percentage compared with the pre-treatment data. As well, the mean sperm DFI was significantly improved compared with the pre-treatment data; in men that underwent varicocelectomy (34.6% vs. 28.3%), in men on MC stabilizer only (33.4% vs. 27.8%), and in men that underwent varicocelectomy followed by MC stabilizer (34.3% vs. 25.1%). Sperm DFI improvement percentages showed the highest improvement in men that underwent varicocelectomy followed with MC stabilizer compared with the other two groups (26.8% vs. 18.2%, 16.8%). Sperm DFI improvement percentages showed significant increases in the infertile patients with Vx grade III compared to Vx grade II in all investigated groups. It is concluded that in infertile men associated with Vx and high sperm DFI, surgical repair followed with MCs stabilizer significantly improve sperm DFI compared with either surgical repair or MCs stabilizer alone.