BACKGROUND Succinylcholine remains the gold standard and satisfactory muscles relaxants for endo tracheal intubation. The aims of this study to assess three minimum dose of Succinylcholine for tracheal intubation as the modern balance anaesthesia consist of amnesia, analgesia & muscles relaxation. MATERIAL & METHODS 60 adults patient of ASA grade I & II posted for elective surgery under general anaestheisa who also required endo tracheal intubation, was induced with inj. fentanyl,  2 mcg / kg.  and propofol 2 mg / kg. iv. The patient were randomly allocated in to three groups according to dose of succinylcholine [0.4 mg/kg., 0.6 mg/kg. & 1 mg/kg.]. The overall intubation condition assessed after 60 seconds of succinylcholine inj. R­ESULT The acceptable intubating condition (excellent & good grade combined) were obtained in 65%, 100%, 100% of the patient who received 0.4 mg, 0.6 mg & 1 mg/kg of Succinylcholine respectively, P<0.001, excellent intubation condition were obtained in 51%, 96% and 100% of the patient after 0.4, 0.6 and 1 mg/kg of Succinylcholine respectively P<0.001. CONCLUSION The 0.6 mg/kg Succinylcholine can be used as minimum intubating dose as it provide acceptable intubating condition within 60 seconds as compared to 1 mg / kg which may be excessive. Duration of action of Succinylcholine is dose dependent & reducing the dose allow a more rapid return of spontaneous respiration, reflexes and decreases the apnoea time.

Background and Aim Suppression of deleterious effect of pneumoperitoneum is a very important goal of laparoscopic surgeries. Dexmedetomidine is a highly selective ?2-adrenoreceptor agonist that causes centrally mediated reduction of sympathetic nervous system activity and lead to sedation and analgesia. The aim of our study was to evaluate the effect of dexmedetomidine on haemodynamic response of intraoperative events like laryngoscopy, endotracheal intubation, pneumoperitoneum and extubation time, and sedation during and after laproscopic hysterectomy. Methods A prospective, randomised and double blind study was done on 50 female patients, undergoing laparoscopic total hysterectomy. All patients were randomly allocated into two groups; group D (dexmedetomidine) and group C (normal saline). Group D received inj dexmedetomidine 1 ?g/kg, diluted in 50 ml of normal saline over 15 min of duration and 0.4 ?g/kg/h infusion was started till the pneumoperitoneum continues. Group C patients receive normal saline infusion. Parameter recorded was heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP), SPO2 and ETCO2. Assessment of sedation was done at extubation than every 15 min for 2 h by Ramsay sedation score (RSS). Results Among haemodynamic profile, mean arterial pressure and HR after drug administration were significantly lower in perioperative period, particularly at intubation and extubation time in dexmedetomidine (group D) as compared with controls (group C). The extubation time was significantly lower in the dexmedetomidine groups than in the control group. No significant change was seen in the sedation score in both the groups. Conclusion Dexmedetomidine use during laparoscopic hysterectomy leads to attenuation of hemodynamic response to pneumoperitonium and decrease in extubation time with no change in sedation level of the patients.

INTRODUCTION Ketamine is a well known agent for sedation for short surgical procedures due to its very good analgesic action. But it has cardio stimulatory response and recovery from anaesthesia after Ketamine use is complicated by delirium and hallucination. In studies it is proved that these side effects can be reduced by premedication with benzodiazepines. The α2 adrenoceptor agonists are becoming popular for their properties like haemodynamic stability and reducing anaesthetic requirement. AIM This study was planned to see the effects of Dexmedetomidine on emergent reaction of Ketamine, when used as premedication agent with Ketamine for conducting short surgeries in adult patients. MATERIALS AND METHODS Study was conducted in 90 ASA class I and II male and female patients of age between 18-40 undergoing short procedures like laparoscopic ligation, skin grafting, dilatation and curettage, endoscopic procedures, excision of small swelling, etc. Patients were randomly divided into three groups of 30 each as follows: Group K: after premedication with inj. glycopyrrolate 0.01mg/kg, inj. Ketamine 2mg/kg, Group M: after premedication with inj. glycopyrrolate 0.01mg/kg and inj midazolam 0.05mg/kg, inj. Ketamine 2mg/kg, Group D: after premedication with inj glycopyrrolate 0.01 mg/kg and inj. Dexmedetomidine 0.5μg/kg, Ketamine 2mg/kg was given. Observations were made for cardiovascular response to invasive procedure, post anaesthetic anxiety and delirium with help of Memorial Delirium Assessment scale (MDAS). RESULTS Midazolam reduced delirium to a greater level, but in comparison to control group and midazolam group, dexmedetomidine reduced delirium to a much greater level (p-value<0.001). Postoperative pain was less in Dexmedetomidine group (p-value< 0.001). CONCLUSION Dexmedetomidine reduced delirium caused by Ketamine when used as a premedication agent. It produced more haemodynamic stable patients. Postoperative analgesia was also better.

Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization.

Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-β-d-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells.

Among all neural tube defects, encephalocele incidents are 1 in 5000 live births.((1)) Newborn with encephalocele may be associated with other congenital malformations. Encephalocele patient's management pose many challenge to neurosurgeon due to other associated anomalies that may present like ventriculocele, Dandy Walker and Arnold-Chiari malformation, and difficult positioning airway management to anaesthesiologist. We discuss a case of huge encephalocele and its management.

One of the several challenges to the anaesthesiologists, is management of child with difficult airway. Management of even normal airway in a neonate is different and complex as compared to airway of two year old child and that of adult. Definition of the difficult airway is related solely to tracheal intubation or problems with mask ventilation1.Among the different causes of difficult airway cranio facial and neoplastic anomalies are very common. We present a case report of difficult airway management in encephalocele patient.

Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P<0.01) and increased expression of ER-β target TNF-α (P<0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization.

Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5M (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ss and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity. Copyright (c) 2014 John Wiley & Sons, Ltd.

The integral membrane channel protein aquaporin (AQP) is aberrantly expressed with oncogenic characteristics in various human cancers. In this study, we analyzed the expression pattern of all subtypes of AQPs, and found that 8 out of 13 AQPs expressed in melanoma cells. To understand the role of aberrant expression of AQP in this disease, we over-expressed AQP3 and AQP9 in human melanoma WM266.4 cells and found that both AQPs significantly increased the chemoresistance of WM266.4 cells to arsenite. Functional studies showed that AQP3 and AQP9 can inhibit cell apoptosis induced by arsenite through down-regulating p53 and up-regulating Bcl-2 and XIAP. Our data suggest the implication of APQ in melanoma progression and that the over-expression of AQP3 and AQP9 contributes to the chemoresistance of melanoma to arsenite.

Lung cancer is the leading cause of cancer deaths worldwide and over 80% of lung cancer patients are classified as having non-small cell lung cancer. Although there have been technological advancements in the early detection and standard treatment of lung cancer, it is often diagnosed at an advanced stage and is chemoresistant to most available drugs. A number of studies have demonstrated that microRNA is able to modulate various tumorigenic processes, including progression and metastasis, in various mechanisms. In this review we examine the most recent achievements in microRNA and lung cancer treatment and summarize the research progress on the reciprocal regulation between microRNA and epigenetic modifications, as both have been intensively studied in lung cancer. Epigenetic modifications on the human genome regulate gene and microRNA expression at the transcriptional level; inversely, microRNA can also transcriptionally cleave and/or translationally repress the expression of several key enzymes involved in epigenetic processes such as DNA methylation and histone modification. Better understanding of reciprocal regulation between microRNA and epigenetic modifications will underlie the development of novel microRNA orientated diagnostic and therapeutic strategies relating to lung cancer in the near future.

ABSTRACT Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro . Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas . We report here the in vitro activities, structure-activity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro , the new compounds appeared to be safer than N-9 for vaginal use.

A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47% Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction) QSAR suggested structures with more cyclic and branched moieties, increased topological separation of 0 and N therein, and reduced solvation connectivity index for better activity Pharmacokinetic study with compound 10 at an oral dose of 10 0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood brain barrier A 10-fold decrease in PSA and 15-fold increase in ER-beta gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-beta mediated actions The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia

BACKGROUND:We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane. METHODS:Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity. RESULTS:Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at > or =0.002% concentration with hyper-polarization of sperm membrane potential (P < 0.001), intracellular alkalinization (P < 0.01), ROS generation (P < 0.05) and no apparent effect on sperm (n = 150) membrane structure. Isoxazolecarbaldehyde compounds required > or =0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P < 0.001), intracellular acidification (P < 0.01) and ROS generation (P < 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at > or =0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P < 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 microg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg). CONCLUSIONS:The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal contraceptive. CDRI Communication No. 7545.

Twenty seven derivatives (2–28) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol were synthesized and evaluated for anti-trichomonas, spermicidal and antifungal activities. Twenty six compounds were active against Trichomonas vaginalis at MIC ranging from 1–42 μM and seven compounds (9,18,19,22,24,26,28) immobilized 100% human spermatozoa at 1% concentration (w/v). Twenty three compounds (2,3,5,8–26,28) exhibited antifungal activity at 25–50 μg/mL concentration. Seven compounds (9,18,19,22,24,26,28) showed significant anti-trichomonas and spermicidal activities and also exhibited mild antifungal activity. All the compounds were highly safe towards human cervical cell line (HeLa) as shown by the cell-viability assay of HeLa cells at 200 μg/mL concentration, whereas nonoxynol-9 (N-9, the marketed spermicidal microbicide) was highly cytotoxic. Therefore, it may be concluded that introduction of the pharmacophore responsible for spermicidal activity into a proven anti-trichomonas structure may lead to a potent dual function microbicide better and safer than N-9.