Effects of intravenous single-bolus lidocaine infusion versus intravenous single-bolus magnesium sulfate infusion on postoperative pain, emotional status, and quality of life in patients undergoing spine fusion surgery: a randomized study.

BACKGROUND: We assessed the efficiency of intravenous adjuvants in decreasing opioid intake and pain scores after spine fusion surgery. METHODS: This study included 120 patients aged 18-60 listed for spine fusion surgery under general anesthesia. Patients were randomly assigned to four groups: Group (Lidocaine): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min. Group (Magnesium): received IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (combined Lidocaine and Magnesium): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min.+IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (Control): received IV saline 50 mL. The time to the first request analgesia, the postoperative pain score, total analgesic use, patient satisfaction, anxiety, depression, mental state, quality of life, and side effects were measured. RESULTS: The combined group had more extended time for the first analgesic request and fewer rescue analgesia doses than the other groups. NRS scores at rest or movement were statistically significantly lower in the lidocaine group and the combined group compared to the control group (P1, P3<0.05) at almost all times. This combination reduces anxiety and depression and improves overall health up to three months after a single infusion. The combined group had higher patient satisfaction. CONCLUSIONS: A synergistic effect of a combination of lidocaine and magnesium sulfate on perioperative pain was found. It reduces analgesic consumption, depression, and anxiety and improves overall health up to three months after a single infusion dose.

Efficacy of intratracheal dexmedetomidine on recovery from general anaesthesia in paediatric patients undergoing lower abdominal surgeries: A randomised controlled trial.

BACKGROUND: This study investigated the effectiveness of intratracheal dexmedetomidine in reducing untoward laryngeal responses in paediatrics undergoing lower abdominal surgeries. METHODS: This trial included 60 patients divided into two groups scheduled for lower abdominal surgeries. Group D were given intratracheal dexmedetomidine at a dosage of 0.5mg/kg, while Group C received intratracheal saline (0.9%). The cough severity score, the Paediatric Objective Pain Scale for pain assessment, awareness, extubation, emergence agitation score, Ramsay sedation score and adverse effects were recorded. RESULTS: There was a significant difference in the incidence of coughing severity between Groups D and C both at extubation and after five minutes of extubation (p < 0.001). The median scores of the Paediatric Objective Pain Scales and the median agitation scales of Group D were significantly lower over the first four hours (p < 0.050). The mean time to first request rescue analgesia was significantly longer in the D group than in the control group (p < 0.001). The mean total consumption of rescue analgesia in the first 24 hours postoperatively was significantly lower in the dexmedetomidine group (p < 0.050). Awareness and extubation times were comparable in both groups, and none of the subjects reported any adverse effects. CONCLUSION: In the current study, lower abdominal surgery patients who received intratracheal dexmedetomidine at a dose of 0.5mg/kg 30 minutes before the completion of the procedure experienced smooth extubation and balanced anaesthetic recovery.

First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT6 Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.

Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT6 emerged as a promising target for AD treatment; thus, here a new series of 5-HT6R ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HT6R affinity and selectivity over 5-HT1AR (13-15), 5-HT7R (14 and 15), and 5-HT2AR (13). Compound 15 displayed high selectivity for 5-HT6R over other central nervous system receptors and exhibited low risk of cardio-, hepato-, and nephrotoxicity and no mutagenicity, indicating its "drug-like" potential. Compound 15 also demonstrated neuroprotection against rotenone-induced neurotoxicity as well as antioxidant and glutathione peroxidase (GPx)-like activity and regulated antioxidant and pro-inflammatory genes and NRF2 nuclear translocation. In rats, 15 showed satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. 15's neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the way for the use of selenotriazines to inhibit both causes and symptoms in AD therapy.

Add dexmedetomidine to levobupivacaine for transversus abdominis plane block in elderly patients undergoing inguinal hernia repair: Could it make a difference? A randomised trial.

BACKGROUND: Transversus abdominis plane block is becoming more common as part of multimodal analgesia for post-abdominal operation pain relief. This study compared the analgesic effects of adding dexmedetomidine to levobupivacaine (transversus abdominis plane) block in elderly patients undergoing inguinal hernia surgery to adding fentanyl. METHODS: Overall, 90 elderly patients with a simple inguinal hernia repair were randomly assigned to one of three groups. After spinal anaesthesia, an ultrasound-guided transversus abdominis plane block was performed. Transversus abdominis plane block was accomplished with 0.25% levobupivacaine + 0.9% normal saline in Group L (n = 30) (20mL). Transversus abdominis plane block was accomplished with 0.25% levobupivacaine + 1 µg/kg dexmedetomidine in Group D (n = 30) (20mL). Transversus abdominis plane block was obtained with 0.25% levobupivacaine + 1 µg/kg fentanyl in Group F (n = 30) (20mL). The primary outcome was the first analgesic request, and the secondary outcomes were the visual analog scale, postoperative analgesic requirements, sedation, hemodynamic stability, and related complications 24 hours postoperatively. 1gm paracetamol intravenously was provided as rescue analgesia. RESULTS: The time to first analgesic request in the dexmedetomidine group was substantially more prolonged than in the fentanyl and control groups (516.5±27.8, 451.2±11.1, and 403.9±10.5min, respectively; p < 0.05). Postoperative analgesic requirements were significantly decreased in dexmedetomidine 1(1-2) than control 2(1-3) and fentanyl 1.5(1-2) respectively (P<0.01). VAS was significantly lower in Group D and Group F than in Group L postoperatively. No significant difference in side effects was noted between the groups. CONCLUSION: The transversus abdominis plane block is the best multimodal analgesia choice for inguinal hernia repair in older patients. Combining dexmedetomidine with levobupivacaine in the transversus abdominis plane block can improve the quality of postoperative analgesia while avoiding significant side effects.

Efficacy of Levobupivacaine Versus Levobupivacaine Plus Dexmedetomidine Infiltration for Post-Tonsillectomy Analgesia: A Randomized Controlled Trial.

Background: The study evaluated the analgesic effects of levobupivacaine infiltration in the tonsil bed, and a combination of levobupivacaine and dexmedetomidine in patients undergoing tonsillectomy. Methods: Ninety children (ages 3 to 7 years) who were scheduled for a tonsillectomy were allocated randomly into two groups. (L Group): peritonsillar infiltration with 0.25% levobupivacaine (2 ml + 0.5 ml saline 0.9% per tonsil). (LD Group): levobupivacaine 0.25% (2 ml) plus dexmedetomidine 1 µg/kg diluted in 1 ml saline 0.9% (0.5 ml in each tonsil), and administered by peritonsillar infiltration (2.5 ml per tonsil) following intubation 3-5 minutes before operation. To avoid bias, infiltrate a total volume of 2.5 ml in each tonsil. The first analgesic request time was the primary outcome, with postoperative pain score, total analgesic consumption, total oral intake, sedation, and side effects as secondary outcomes. Results: The first rescue analgesia time in the LD group was longer (644.31 ± 112.89 min) than in the L group (551.51 ± 146.16 min, P-value <0.001). The number of patients who required >1 analgesic dose in the L group (n = 13) was higher than in the LD group (n = 5). The LD group consumes a lower total dose of IV paracetamol in the first 24 hours postoperatively (321.89 ± 93.25 mg) than the L group (394.89 ± 183.71 mg, P < 0.00-value < 0.050). On the first day postoperatively, patients in the LD group had a higher total oral intake (P < 0.001). Except for a slight increase in laryngospasm in the L group, there were no side effects. Conclusions: The Children's peritonsillar infiltration of levobupivacaine and dexmedetomidine improved postoperative pain after adenotonsillectomy. The topically applied levobupivacaine and dexmedetomidine were concomitant with no systemic effects, greater total oral intake on the first day postoperative, and higher family satisfaction.

Seleno-vs. thioether triazine derivatives in search for new anticancer agents overcoming multidrug resistance in lymphoma.

Lymphomas are still difficult to treat even with modern therapies as, among others, multidrug resistance (MDR) is often counteracting a successful cancer therapy. P-gp/ABC-transporters are well-known for their crucial role in the main tumour MDR mechanism, eliminating drugs and cytotoxic substances from the cancer cell by efflux, and their modulators are promising for innovative therapy, but none has been approved in the pharmaceutical market yet. Herein, we have designed, synthesised and analysed 30 novel seleno- and thioether 1,3,5-triazine derivatives conducting comprehensive studies to evaluate their potential application in human JURKAT lymphoma cells. Among the new compounds, four (11, 12, 13 and 23) were much more effective than the reference inhibitor verapamil, being potent ABCB1 inhibitors already at 2 µM, while 5 and 15 showed very potent ABCB1 inhibitory activity only at 20 µM. Results of P-gp ATPase assays, supported with docking studies, indicated the competitive substrate mode of modulating action for 15, while ABCB1, ABCC1 and ABCG2 genes expression induction by 15 with q-PCR was confirmed. All compounds were evaluated for their cytotoxic and antiproliferative properties in both sensitive (PAR) and resistant (MDR) mouse T-lymphoma cell lines, and compound 15, also considering its promising ABCB1 inhibition properties, was revealed to be the best compound in terms of its cytotoxic effect (IC50: 16.73 µM) as well as concerning the antiproliferative effect (IC50: 5.35 µM) in MDR cells. Regarding the mechanistic studies looking at the cell cycle, the thioether 15 and selenium derivatives 26 and 29 were significantly effective in the regulation of cell cycle-related genes alone or in co-treatment with doxorubicin counteracting Cyclin D1 and E1 expression and increasing p53 and p21 levels, shedding first light on their mechanism of action. In summary, we explored the chemical space of seleno- and thioether 1,3,5-triazine derivatives with interesting activity against lymphoma. Especially compound 15 is worthy of being studied deeper to evaluate its precise mode of action further as well it can be improved regarding its potency and drug-likeness.

Comparison of the effect of adding midazolam versus fentanyl to intrathecal levobupivacaine in patients undergoing cesarean section: double-blind, randomized clinical trial.

BACKGROUND: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathecal levobupivacaine in women undergoing cesarean delivery. METHODS: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 µg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. RESULTS: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. CONCLUSION: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 µg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.

An exit beyond the pharmacophore model for 5-HT6R agents - a new strategy to gain dual 5-HT6/5-HT2A action for triazine derivatives with procognitive potential.

This research allowed us to find the first highly potent 5-HT6/5-HT2A receptor (5-HT6/5-HT2AR) dual antagonists in a group of 1,3,5-triazine compounds as a result of an exit beyond the hydrophobic feature of the pharmacophore model for 5-HT6R antagonists. Design and synthesis of the series (2-16) of new O- and S-containing ether derivatives of 1,3,5-triazines with the double-ring aromatic region have been performed. The new compounds were examined within the comprehensive pharmacological screening, including: radioligand binding assays, functional and ADMET studies in vitro as well as behavioral tests in rats. Crystallographic aspects and computer-aided structure-activity relationship were analyzed, as well. The comprehensive approach led to selection of compound 12 (4-(4-methylpiperazin-1-yl)-6-(2-(naphthalen-2-ylthio)propan-2-yl)-1,3,5-triazin-2-amine) with the most significant dual 5-HT6/5-HT2AR antagonistic action (5-HT6R Ki = 11 nM, 5-HT2AR Ki = 39 nM). Moreover, the compound 12 has satisfactory ADMETox properties in vitro, i.e.: the high permeability through biological membranes, high metabolic stability, neither mutagenic nor hepatotoxic effects, and moderate ability to inhibit CYP3A4. Above all, 12 showed ability to reverse the pharmacologically-induced (MK-801) memory impairment at low doses (1-3 mg/kg) in Novel Object Recognition (NOR) test in rats. Our results indicate a promising potency of dual 5-HT6/5-HT2AR antagonism in the search for novel strategy to fight Alzheimer's disease, which remains an unmet clinical need.

End-tidal carbon dioxide measurements as a surrogate to arterial carbon dioxide during pediatric laparoscopic surgeries: a prospective observational cohort study.

BACKGROUND: Maintaining normocapnia during mechanical ventilation in anesthetized children during laparoscopic surgeries is highly recommended. There is a debate regarding the use of capnography (ETCO2) as a trend monitor for evaluation of arterial carbon dioxide levels (PaCO2). We analyzed the relationship between ETCO2 and PaCO2 with time in elective pediatric laparoscopic surgeries. METHODS: This study was a prospective observational cohort analysis of 116 paired comparisons between PaCO2 and ETCO2 computed from 29 children (ASA I, 12-72 months). Arterial blood samples were withdrawn before, at 15 minutes and 30 minutes during pneumoperitoneum and 1 minute after deflation. ETCO2 value was recorded simultaneously, while arterial blood was withdrawn. PaCO2-ETCO2 relationship was evaluated by Pearson's correlation coefficients and Bland Altman Method of agreement. RESULTS: Out of the 116 comparisons analyzed, a PaCO2-ETCO2 difference beyond 0 to ≤ 5 mmHg was recorded in 71 comparisons (61.2%) with negative difference in 34 comparisons (29.3%). A positive significant correlation between PaCO2 and ETCO2 was recorded before (r = 0.617, p = 0.000) and at 15 minutes (r = 0.582, p = 0.001), with no significant correlation at 30 minutes (r = 0.142, p = 0.461), either after deflation (r = 0.108, p = 0.577). Bland-Altman plots showed agreement between ETCO2 and PaCO2 before inflation with mean PaCO2-ETCO2 difference 0.14 ± 5.6 mmHg (limits of 95% agreement -10.84-11.2, simple linear regression testing p-value 0.971), with no agreement at 15 minutes (0.51 ± 7.15, -13.5-14.5, p = 0.000), 30 minutes. (2.62 ± 7.83, -12.73-17.97, p = 0.000), or after deflation (1.81 ± 6.56, -10.93-14.55, p = 0.015). CONCLUSION: Usage of capnography as a trend monitor in pediatric laparoscopic surgeries may not be a reliable surrogate for PaCO2 levels. TRIAL REGISTRATION: Clinical Trials. gov (Identifier: NCT03361657).

The innovative potential of selenium-containing agents for fighting cancer and viral infections.

Selenium-containing compounds have emerged as a potentially promising treatment for viral infections and tumor development and dissemination. Selenium per se is often considered as a toxic element with little or no beneficial effects, but considerable advances have been made in the understanding of the complex biology, chemistry and drug delivery of this element, especially when it is included in bioactive molecules. Here, we summarize and critically discuss recent findings in the field of selenium-based applications for the treatment of cancer and viral infections.

Conjoined twins: A report of four cases.

BACKGROUND: Conjoined twin is a rarely seen congenital anomaly associated with significant morbidity and mortality. The most common types of conjoined twins are thoracopagus. Conjoined twins are either symmetrical twins or asymmetrical or heteropagus. This report records the successful separation of 2 cases of asymmetrical twins and one symmetrical twin with fused livers and diaphragm and communicating peritoneal cavities. PATIENTS AND METHODS: This study amended and strictly followed the ethical guidelines of the Helsinki declaration, our study included 4 case reports on conjoined twins (CT), 2 male and three female patients; 3 of them were parasitic and one was conjoined. We operated upon 2 parasitics and one conjoined. The 1st case died preoperatively. RESULTS: Four living children is our result. CONCLUSION: As connections between the bowel and bone of the parasite and the respective organs in the autosite are often absent, the parasite could be excised easily without any effect on the autosite. We recommend the separation of the parasite and the autosite as early as possible. In many cases, surgery results in the death of one or both of the conjoined twins, particularly if they are joined at the head or share a vital organ. Our separated twins are yet the youngest living separated twins. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03388684.

Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma.

Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5-7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.

Synthesis and computer-aided SAR studies for derivatives of phenoxyalkyl-1,3,5-triazine as the new potent ligands for serotonin receptors 5-HT6.

This research has provided the most active 5-HT6R agents among 1,3,5-triazine derivatives investigated to date and has also identified the world's first selenium-containing 5-HT6R ligands. The studies are focused on design, synthesis, biological evaluation and docking-supported SAR analysis for novel 5-HT6R agents as derivatives of lead structure 4-(4-methylpiperazin-1-yl)-6-(phenoxymethyl)-1,3,5-triazin-2-amine (7). The lead modifications included an introduction of: (i) various small substituents at benzene ring, (ii) a branched ether linker or (iii) the ether oxygen replacement with other chalcogen (S, Se) or sulfonyl moiety. Hence, a series of new compounds (7-24) was synthesized and examined on their affinities for 5-HT6R and selectivity, in respect to the 5-HT1AR, 5-HT2AR, 5-HT7R and dopamine D2 receptor, in the radioligand binding assays. For representative most active compounds functional bioassays and toxicity profile in vitro and antidepressant-like activity in vivo were examined. The 2-isopropyl-5-methylphenyl derivative (10) was found as the most active triazine 5-HT6R antagonist (Ki = 11 nM). SAR analysis indicated, that an exchange of oxygen to selenium (7 vs. 22), and especially, to sulfur (7 vs. 19) was beneficial to increase both affinity and antagonistic action for 5-HT6R. Surprisingly, an introduction of SO2 caused a drastic decrease of the 5-HT6R affinity, which was explained at a molecular level based on docking studies. All in vivo tested compounds (10, 18 and 21) did not show any risk of toxicity in the safety studies in vitro.

Epidural dexmedetomidine infusion for perioperative analgesia in patients undergoing abdominal cancer surgery: randomized trial.

OBJECTIVE: To assess the postoperative analgesic efficacy of epidural dexmedetomidine added to bupivacaine infusion for patients undergoing major abdominal cancer surgery. METHODS: Patients scheduled for major upper abdominal cancer surgery were allocated to group bupivacaine (n =32), in which patients received epidural bupivacaine infusion (6 mL/h bupivacaine 0.1%) for 48 hours postoperatively, or group bupivacaine + dexmedetomidine (n=32), in which patients received epidural dexmedetomidine added to bupivacaine infusion (6 mL/h of bupivacaine 0.1% + dexmedetomidine, 0.5 µg/mL) for 48 hours postoperatively. The cumulative morphine consumption, the time to first analgesic request, and the VAS pain score were evaluated. RESULTS: The cumulative morphine consumption was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine: mean ± SD of 10.40±5.16 mg vs 23.23±8.37 mg with an estimated difference (95% CI) of -12.83 (-16.43, -9.24), (P<0.001). The time to the first analgesic demand was significantly delayed in group bupivacaine + dexmedetomidine compared with group bupivacaine: median (IQR) of 6 (1.75, 8.25) h vs 1 (0, 4)h, (P<0.001). The mean collapsed over time of overall VAS pain scores at rest and movement was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine : mean ± SE of 1.6±0.08 vs 2.38±0.08 with an estimated difference (95% CI) of -0.8 (-1, -0.86), (P<0.001), and mean ± SE of 2.17±0.07 vs 3.25±0.07 with an estimated difference (95% CI) of -1.1 (-1.27, - 0.89), (P<0.001), respectively. CONCLUSION: Epidural infusion of dexmedetomidine added to bupivacaine for patients undergoing major abdominal cancer surgery significantly reduced morphine consumption, delayed time to first analgesic supplementation, and decreased pain intensity during the first 48 hours postoperatively without harmful derangement on hemodynamics.

Computer-Aided Studies for Novel Arylhydantoin 1,3,5-Triazine Derivatives as 5-HT6 Serotonin Receptor Ligands with Antidepressive-Like, Anxiolytic and Antiobesity Action In Vivo.

This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamine D2 receptors were evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT6 receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as "druglikeness" in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as the most active 5-HT6R agents within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, the most active one in the series (5-HT6R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6⁻197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds form with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro.

Selenides and Diselenides: A Review of Their Anticancer and Chemopreventive Activity.

Selenium and selenocompounds have attracted the attention and the efforts of scientists worldwide due to their promising potential applications in cancer prevention and/or treatment. Different organic selenocompounds, with diverse functional groups that contain selenium, have been reported to exhibit anticancer and/or chemopreventive activity. Among them, selenocyanates, selenoureas, selenoesters, selenium-containing heterocycles, selenium nanoparticles, selenides and diselenides have been considered in the search for efficiency in prevention and treatment of cancer and other related diseases. In this review, we focus our attention on the potential applications of selenides and diselenides in cancer prevention and treatment that have been reported so far. The around 80 selenides and diselenides selected herein as representative compounds include promising antioxidant, prooxidant, redox-modulating, chemopreventive, anticancer, cytotoxic and radioprotective compounds, among other activities. The aim of this work is to highlight the possibilities that these novel organic selenocompounds can offer in an effort to contribute to inspire medicinal chemists in their search of new promising derivatives.

Effect of tramadol addiction alone and its co-abuse with cannabis on urinary excretion of Copper, Zinc, and Calcium among Egyptian addicts.

BACKGROUND: The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases. OBJECTIVE: The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis. METHODS: Sixty-five males were included in the study, they were classified into control group (G1=19), tramadol addicts group (G2=18), and tramadol coabused with cannabis addicts group (G3=28). Parameters investigated for structural integrity were urinary levels ofleucineaminopeptidase and N-acetyl-ß-D-glucosaminidase, and urinary parameters for reabsorption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated. RESULTS: Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups. CONCLUSION: Both tramadol addiction alone or coabused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.

The Reactive Sulfur Species Concept: 15 Years On.

Fifteen years ago, in 2001, the concept of "Reactive Sulfur Species" or RSS was advocated as a working hypothesis. Since then various organic as well as inorganic RSS have attracted considerable interest and stimulated many new and often unexpected avenues in research and product development. During this time, it has become apparent that molecules with sulfur-containing functional groups are not just the passive "victims" of oxidative stress or simple conveyors of signals in cells, but can also be stressors in their own right, with pivotal roles in cellular function and homeostasis. Many "exotic" sulfur-based compounds, often of natural origin, have entered the fray in the context of nutrition, ageing, chemoprevention and therapy. In parallel, the field of inorganic RSS has come to the forefront of research, with short-lived yet metabolically important intermediates, such as various sulfur-nitrogen species and polysulfides (Sx2-), playing important roles. Between 2003 and 2005 several breath-taking discoveries emerged characterising unusual sulfur redox states in biology, and since then the truly unique role of sulfur-dependent redox systems has become apparent. Following these discoveries, over the last decade a "hunt" and, more recently, mining for such modifications has begun-and still continues-often in conjunction with new, innovative and complex labelling and analytical methods to capture the (entire) sulfur "redoxome". A key distinction for RSS is that, unlike oxygen or nitrogen, sulfur not only forms a plethora of specific reactive species, but sulfur also targets itself, as sulfur containing molecules, i.e., peptides, proteins and enzymes, preferentially react with RSS. Not surprisingly, today this sulfur-centred redox signalling and control inside the living cell is a burning issue, which has moved on from the predominantly thiol/disulfide biochemistry of the past to a complex labyrinth of interacting signalling and control pathways which involve various sulfur oxidation states, sulfur species and reactions. RSS are omnipresent and, in some instances, are even considered as the true bearers of redox control, perhaps being more important than the Reactive Oxygen Species (ROS) or Reactive Nitrogen Species (RNS) which for decades have dominated the redox field. In other(s) words, in 2017, sulfur redox is "on the rise", and the idea of RSS resonates throughout the Life Sciences. Still, the RSS story isn't over yet. Many RSS are at the heart of "mistaken identities" which urgently require clarification and may even provide the foundations for further scientific revolutions in the years to come. In light of these developments, it is therefore the perfect time to revisit the original hypotheses, to select highlights in the field and to question and eventually update our concept of "Reactive Sulfur Species".