Prostaglandin Synthetase Inhibitor Research Articles

A STUDY ON MATERNAL AND FETAL OUTCOME IN OLIGOHYDRAMNIOS

Background: Amniotic fluid provides a protected milieu for growing fetus, cushioning the fetus against mechanical and biological injury. It also supplies nutrients and facilitates growth and movement.Oligohydramnios is defined as Amniotic fluid index (AFI) less than 5 cm, or deep vertical pocket < 21. It occurs in 1–5% pregnancies at term, with the incidence increasing in postdate pregnancies to 11%.2 Maternal conditions associated with decreased AFV ( amniotic fluid volume)include post-dated pregnancy, preterm premature rupture of membranes (PPROM), hypertension, autoimmune disorders and maternal medication like prostaglandin synthetase inhibitors. Fetal factors: Which influence AFV are essentially related to fetal growth (intrauterine growth restriction) and fetal anomalies, particularly of the renal tract. The most commonly associated renal anomalies with oligohydramnios include bilateral renal agenesis, multicystic dysplastic kidneys, bladder outlet obstruction and infantile polycystic kidney disease.The aim of this study is to evaluate the etiological risk factors of oligohydramnios and to know the clinical significance and mode of delivery and maternal and perinatal outcome. Methods: This was a retrospective study conducted on 100 cases in Basaveshwar Medical and Teaching Hospital attached to MahadevappaRampure Medical college, Kalaburagi from 1-8-2023 to 1-6-2024.All cases coming to Basaveshwar medical and teaching hospital with oligohydramnios were included in the study after fulfilling inclusion and exclusion criteria Results: Of the 100 cases in the present study,40 cases were in 25-30 years accounting for 40% of cases with maximum number of cases in this age group.56 cases were primigravida accounting for 56% of cases with majority of cases being primigravida and 44 cases were multigravida accounting for 44% of cases.The number of cases with preterm rupture of membranes were 21 ( 21%), cases with Intra uterine growth restriction were 15 (15%). 6 cases (6%) had congenital anamolies. The number of cases withpost dated pregnancy were 22 (22%), Pregnancy induced hypertension cases were 28 (28%). Cases with autoimmune diseases were 1 (1%) and 7 cases (7%) were idiopathic.The most important cause for oligohydramnios was pregnancy induced hypertension and post-dated pregnancy. 13 of the cases had spontaneous onset of labouri.e 13% cases, 28 cases (28%) were induced and 59 cases underwent cesarean section accounting for 59% of all cases.In the present study, total of 19 cases underwent cesarean section because of fetal distress accounting for 19% of cases with the most common indication for cesarean section.11 cases (11%) underwent LSCS due to IUGR, ,4 cases (4%) underwent cesarean section because of non-progression of labour, 2 cases(2%) underwent LSCS because of malpresentation/malposition, 9 cases (9%) had cephalopelvic disproportion, 2 cases (2%) refused for induction of labour and 12 cases (12%) were previous LSCS.Among the 100 cases studied ,there were 8 cases (8%) with meconium aspiration syndrome, 5 cases (5%) had respiratory distress, 6 cases (6%) had low birth weight, 6 cases (6%) with congenital anomalies, 21 cases (21%)had NICU admissions, 4 cases (4%) were still born and 2 cases(2%) had intrauterine fetal death Conclusion: Oligohydramnios is associated with fetal distress, meconium aspiration syndrome ,respiratory distress syndrome ,increased NICU admissions, low birth weight, perinatal mortality, morbidity and increased maternal morbidity due to increased cesarean section rates.Oligohydramnios requires intense fetal monitoring with proper antenatal and intrapartum care.Hence, AFI can be used as a primary tool in fetal surveillance in antenatal and intrapartum period and can help in categorization of fetus into high risk and low risk .One can have favourable outcome with good antenatal and intrapartum care

PREPARATION AND EVALUATION OF MELOXICAM CHEWABLE TABLETS FOR BETTER ORAL DELIVERY

In the current study, meloxicam (MXM) chewable tablets were formulated and evaluated with an aim of improving its solubility, bioavailability and masking its bitter taste in order to create an effective oral drug delivery system. Meloxicam (BCS class II drug), non steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties, acts by inhibition of prostaglandin synthetase leading to inhibition of prostaglandin synthesis. MXM chewable tablets were made by three different techniques: AG (aqueous granulation), NAG (non-aqueous granulation) and DC (direct compression). The chewable tablets of MXM so prepared were assessed for various parameters, namely, palatability test, hardness, weight variation, mechanical strength, disintegration, friability, percent assay and in vitro testing for dissolution profile. The variation found in dissolution profile for all prepared batches was in the order: DC>NAG>AG. The percent assay was found within the range (90-110%). Observations from palatability study showed good overall tolerance levels for DC and AG and moderate tolerance levels for NAG.

"Synthesis and In Silico Analysis of Chalcone Derivatives as Potential Prostaglandin Synthetase Inhibitors"

"Synthesis and In Silico Analysis of Chalcone Derivatives as Potential Prostaglandin Synthetase Inhibitors"

Tolectin in vitro effects on TRP53 gene expression level in gastric adenocarcinoma cells

Tolectin is a non-steroid anti-inflammatory drug (NSAID) which has a clinically analgesic and antipyretic activity. Although the mechanism of its action is not known, tolectin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in humans. Recently, the anticancer effects of tolectin has been reported in in vitro studies. The aim of this study was to investigate the in vitro tolectin effects on antitumor TRP53 gene expression level in gastric adenocarcinoma cells. The gastric adenocarcinoma (AGS) cells were divided to control group and groups treated with 0.0012, 0.0023, 0.0049, 0.0097, 0.0194, 0.0389 mmol/mL. MTT assay method was used to determine the cell viability. Relative TRP53 gene expression level was evaluated by quantitative Real Time PCR. Data were analyzed using ANOVA and student’s t-test. Cell viability significantly decreased in all groups of tolectin treated AGS cells compared to control group; however, expression level of the TRP53 gene did not significantly changed in cells treated with effective concentration of tolectin (0.0131 mmol/mL) compared with control group. Our findings indicated that tolectin has a significant cytotoxic effects on gastric adenocarcinoma cells, however, its effective cytotoxic concentration has not significant impact on antitumor TRP53 gene expression level.

5-Lipoxygenase Contributes to Benzo[a]pyrene-Induced Cytotoxicity and DNA Damage in Human Bronchial Epithelial Cells.

Metabolic activation of indirect-acting carcinogens in target organs is a recognized mechanism of carcinogenesis. This study aimed to determine the role of benzo[a]pyrene (BaP) metabolism enzymes lipoxygenase (LOX), cytochrome P4501A1 (CYP1A1), and prostaglandin synthetase (PGS) in the cytotoxicity and DNA damage induced by BaP in the human tracheobronchial epithelial cells (HBECs) using RNA interference strategy and metabolic enzyme inhibitors. Our results showed that in three epithelial cell lines (HBE, HTR-8/SVneo, and HaCat), BaP significantly upregulated 5-LOX protein expression. 15-LOX-2 expression also increased with increasing BaP concentration, but the change was less pronounced than that of 5-LOX. BaP caused significant cytotoxicity, DNA strand breaks, and 8-hydroxy-2'-deoxyguanosine formation in HBE, which was inhibited by 5-LOXshRNA, a specific inhibitor of 5-LOX (AA861), the CYP1A1 inhibitor α-naphthoflavone, and the PGS inhibitor naproxen. The protective effects of 5-LOXshRNA were stronger than AA861, naproxen and α-naphthoflavone. We conclude that BaP may be activated more by 5-LOX than by CYP1A1 and PGS to produce cytotoxicity and DNA damage in HBE.

C31. Closure of patent ductus arteriosus using intravenous paracetamol : a case series

Abstract Background Although patency of ductal arteriosus is essential for fetal circulation, postnatal ductal closure is critical for postnatal circulation adaptation in order to avoid pulmonary overcirculation with diminished circulation blood flow. Standard medical treatment for patent ductal arteriosus (PDA) consists of pharmacotheraphy and or surgical intervention. Case Summary We present 17 cases of PDA confirmed by echocardiography and was observed for ductal closure after 3 days of intravenous paracetamol intervention (10-15 mg/kg) given every 8 hours. The echocardiography evaluation of PDA status was conducted after those pharmacological intervention and divided based on the gestational age group. In the preterm groups (<36 weeks), 3 cases remained open, 3 cases were closed, and 1 case with reduced flow. In the aterm groups (36-42 weeks), 5 out of 8 cases were closed, while the other 3 showed reduced flow. In the postterm groups (>42 weeks), 1 case was closed and 1 case with reduced flow. Successful rate for PDA closure of each groups were 43%, 62,5% and 50%. Discussion Indomethacin and ibuprofen are standard treaments for PDA closure. However, they have some side effects such as acute renal failure and gastrointestinal complications. From this case series, paracetamol has a promising effect similar to indomethacin and ibuprofen in conducting PDA closure with less side effects. Paracetamol inhibits prostaglandin synthetase activity eventhough its precise mechanism of action remains controversial.

C31. Closure of patent ductus arteriosus using intravenous paracetamol : a case series

Abstract Background Although patency of ductal arteriosus is essential for fetal circulation, postnatal ductal closure is critical for postnatal circulation adaptation in order to avoid pulmonary overcirculation with diminished circulation blood flow. Standard medical treatment for patent ductal arteriosus (PDA) consists of pharmacotheraphy and or surgical intervention. Case Summary We present 17 cases of PDA confirmed by echocardiography and was observed for ductal closure after 3 days of intravenous paracetamol intervention (10-15 mg/kg) given every 8 hours. The echocardiography evaluation of PDA status was conducted after those pharmacological intervention and divided based on the gestational age group. In the preterm groups (<36 weeks), 3 cases remained open, 3 cases were closed, and 1 case with reduced flow. In the aterm groups (36-42 weeks), 5 out of 8 cases were closed, while the other 3 showed reduced flow. In the postterm groups (>42 weeks), 1 case was closed and 1 case with reduced flow. Successful rate for PDA closure of each groups were 43%, 62,5% and 50%. Discussion Indomethacin and ibuprofen are standard treaments for PDA closure. However, they have some side effects such as acute renal failure and gastrointestinal complications. From this case series, paracetamol has a promising effect similar to indomethacin and ibuprofen in conducting PDA closure with less side effects. Paracetamol inhibits prostaglandin synthetase activity eventhough its precise mechanism of action remains controversial.

FORMULATION AND EVALUATION OF PIROXICAM FAST DISSOLVING TABLETS

Piroxicam is an analgesic, antipyretic and anti-inflammatory effects drugs, used to reduce pain, swelling joint stiffness from osteoarthritis, rheumatoid arthritis and by inhibiting prostaglandin synthetase. In the research work, seven formulations (F1 to F7) were prepared direct compression method by using 3 superdisintegrants namely Crospovidone, Crosscarmellose sodium and Sodium starch glycolate in two ratio (1:0.5 and 1:1) and F7 (without superdisintegrant). All the formulations evaluated various post compression parameters thickness, weight variation, disintegration time, hardness, friability, wetting time, drug content water absorption ratio and in- vitro dissolution studies. The best formulation was studied anti-inflammatory activity in rats by using the paw-edema method. Among all formulations (F1) which contains 1:0.5ratio of Croscarmellose sodium, showed to be the optimized formulation as it give good wetting time (51.66 sec), fast disintegration time (29.16 sec), maximum drug release of 99% within 30 minutes and superior anti-inflammatory activity.

Potency and acceptability of oral misoprostol compared with vaginal misoprostol prior to first trimester abortions

Present study was done to assess the effectiveness and acceptability of oral misoprostol compared with vaginal misoprostol for cervical priming before termination of first trimester pregnancy. Recently, prostaglandin E1 analogue misoprostol has caught much attention as cervical priming agent. Prostaglandins are used in different doses and different routes considering the different available results. Misoprostol was originally marketed for prevention of peptic ulcers caused by Prostaglandin synthetase inhibitor (NSAIDS) but now it has a widespread role in obstetric practice specially as a cervical priming agent. The aim of present study is to compare oral misoprostol versus vaginal misoprostol for cervical ripening and to assess its acceptability among women.

Comparative evaluation of the efficacy and safety of Ormeloxifene and combined oral contraceptives in dysfunctional uterine bleeding

Introduction: Dysfunctional Uterine Bleeding (DUB) is an abnormal uterine bleeding, in the absence of any organic, systemic or iatrogenic cause. Pharmacological treatment options available are combined oral contraceptive pills, progestogens, danazol, gonadotrophin releasing hormone (GnRH) agonists, SERMs, prostaglandin synthetase inhibitor, anti-fibrinolytics and ethamsylate. The purpose of the study was to evaluate the efficacy and safety of Ormeloxifene and compare it to combined oral contraceptive pills (OCPs) in dysfunctional uterine bleeding. Method: Hundred women aged 20-50 years presenting with DUB were randomly allocated to two groups of 50 each. Group A were given Ormeloxifene tablet 60 mg twice a week for 12 weeks, followed by 60 mg once a week for 12 weeks. Group B were given OCPs containing 30 microgram Ethinyloestradiol and 150 microgram Levonorgestrel from day 1 to day 21st of the menstrual cycle for 6 cycles. The outcome was studied by assessment of menstrual blood loss by Pictorial Blood loss Assessment Chart (PBAC) score, Hb level in g/dl, endometrial thickness in mm, patient’s level of satisfaction and any drug side effects at the end of 6 months. Results: The reduction in mean PBAC score with Ormeloxifene (330 to 2.8) was significantly more than with oral contraceptive pills (317 to 74) at 6 months (P<0.001). In both the groups mean hemoglobin level increased but rise in Hb in group A (1.5 g/dl) was more as compared to the rise in Hb in group B (1.2 g/dl). The mean endometrial thickness decreased in both the groups but the decrease in group A (9.6 mm to 8.4 mm) was not statistically significant as compared to the decrease in group B (9.8 mm to 6.4 mm). The side effects were minimal in both the groups. 22% patients with Ormeloxifene and 10% with oral contraceptive pills were highly satisfied with their treatment. Conclusion: Ormeloxifene is effective in control of DUB and can be used as an alternative to OCP for treatment of DUB with possibly minimal side effects and better dosage compliance.

Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour.

Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour. We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents. The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses. The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

Combined hormonal contraceptives for heavy menstrual bleeding.

Menorrhagia or heavy menstrual bleeding (HMB) is an excessive blood loss that impairs a woman's quality of life, either physical, emotional, social or material. It is benign and not associated with pregnancy or any other gynaecological or systemic disease. Medical treatments used to reduce excessive menstrual blood loss (MBL) include prostaglandin synthetase inhibitors, antifibrinolytics, oral contraceptive pills, and other hormones. The combined oral contraceptive pill (COCP) is claimed to have a variety of beneficial effects, inducing a regular shedding of a thinner endometrium and inhibiting ovulation, thus having the effect of both treating HMB and providing contraception. More recently, a contraceptive vaginal ring (CVR) has been trialled to investigate whether this treatment can provide similar benefits to COCP while lessening hormonal systemic exposure. This review is an update of a review which originally focused on COCP alone. The scope of the review has been widened to consider other types of delivery of combined hormonal contraceptives for reduction of MBL.To determine the efficacy of combined hormonal contraceptives (pills, vaginal ring or patch) compared with other medical therapies, placebo, or no therapy in the treatment of HMB. A secondary objective was to compare the COCP with the CVR.We searched the Gynecology and Fertility Group trials register, MEDLINE, Embase, CENTRAL, CINAHL and PsycINFO (search dates: Oct 1996, May 2002, June 2004, April 2006, June 2009, July 2017 and September 2018) for all randomised controlled trials (RCTs) of COCP and CVR for the treatment of HMB. We also searched trial registers and the reference lists of retrieved studies for additional trials.We included randomised controlled trials (RCTs) of the use of COCP or CVR compared with no treatment, placebo, or other medical therapies for women with HMB and regular menstrual cycles.All assessments of trial quality and data extraction were performed unblinded by at least two review authors. Our primary review outcomes were treatment success, menstrual bleeding (assessed objectively, semi-objectively or subjectively), and participant satisfaction with treatment. Secondary outcomes were adverse events, quality of life, and haemoglobin level.We identified eight RCTs involving 805 participants. Two trials comparing COCP with placebo were considered to be moderate quality and the remaining studies were low to very low quality, mainly because of serious risk of bias from lack of blinding and concerns over precision.COCP versus placeboCOCP, with a step-down oestrogen and step-up progestogen regimen, improved response to treatment (return to menstrual 'normality') (OR 22.12, 95% CI 4.40 to 111.12; 2 trials; 363 participants; I2 = 50%; moderate-quality evidence), and lowered MBL (OR 5.15, 95% CI 3.16 to 8.40; 2 trials; 339 participants; I2 = 0%; moderate-quality evidence) when compared to placebo. The results suggested that, if the chance of 'successful' treatment was 3% in women taking placebo, then COCP increased this chance from 12% to 77% in women with unacceptable HMB. Minor adverse events, in particular breast pain, were more common with COCP. No study in this comparison reported semi-objectively assessed MBL or participant satisfaction with treatment.COCP versus other medical treatmentsNon-steroidal anti-inflammatory drugs (NSAIDs)There was insufficient evidence to determine whether the COCP reduced MBL when compared to NSAIDs (mefenamic acid and naproxen). No study in this comparison reported semi-objectively assessed MBL, subjectively assessed MBL, participant satisfaction with treatment or adverse events.Levonorgestrel-releasing intrauterine system (LNG IUS)The LNG IUS was more effective than COCP in reducing MBL (OR 0.21, 95% CI 0.09 to 0.48; 2 trials; 151 participants; I2 = 0%; low-quality evidence) but it was not clear whether satisfaction with treatment or adverse effects varied according to which treatment was used. No study in this comparison reported semi-objectively assessed MBL or subjectively assessed MBL.Contraceptive vaginal ring (CVR) versus other medical treatmentsCOCP COCP was compared with CVR in two trials. There were discrepancies between some of the findings and there was no evidence of a benefit for one treatment compared to the other for response to treatment, MBL or participant satisfaction with treatment. There was a greater likelihood of nausea with COCP. No study in this comparison reported objectively assessed MBL or subjectively assessed MBL.ProgestogensCVR was compared to long course progestogens in one trial. It is possible that CVR increased the odds of satisfaction; but we are uncertain whether CVR improved MBL. The evidence was based on small numbers of participants and was very low quality, so definitive conclusions could not be reached. No study in this comparison reported objectively assessed MBL, subjectively assessed MBL, or adverse events.Moderate-quality evidence suggests that the combined oral contraceptive pill over six months reduces HMB in women with unacceptable HMB from 12% to 77% (compared to 3% in women taking placebo). When compared with other medical options for HMB, COCP was less effective than the LNG IUS. Limited evidence suggested that COCP and CVR had similar effects. There was insufficient evidence to determine comparative efficacy of combined hormonal contraceptives with NSAIDs, or long course progestogens.

Effect of Sidaguri (Sidarhombifolia L) on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in osteoarthritis patients

Osteoarthritis (OA) is degenerative and inflammatory joint diseases. Management of OA, until now limited only to overcome the pain, inflammation, and improvement of joint function with medication in the form of NSAIDs that have many side effects. Damage to cells due to the stimulus will free various mediators or substances inflammation such as prostaglandin, IL-6, TNF-α and nitric oxide. Sidaguri plant (Sidarhombifolia L) has anti-inflammatory activity by inhibition of nitric oxide. The mechanism of action Meloxicam, like other NSAIDs, may be associated with the inhibition of prostaglandin synthetase (cyclo-oxygenase). One of the markers of the inflammatory process is CRP and ESR. We tested 50 patients divided into two groups, patients who get Meloxicam and Sidaguri (n = 25) and patients who get Meloxicam and placebo (n = 25). There were significant changes before and after therapy with p-value<0.0001.

Effect of Lipopolysaccharide-Induced Immune Responses on Pregnancy Loss in Ewes

An acute phase response induced by Gram-negative bacteria can reduce pregnancy rate. Early pregnant ewes were used to monitor effects of lipopolysaccharide (LPS), an endotoxin in the outer cell membrane of Gram-negative bacteria, on acute phase/innate immunity response. In Exp. 1, mixed breed ewes were assigned to receive either LPS or LPS and flunixin meglumine, an inhibitor of prostaglandin synthetase, intravenously on day 5 after mating. In Exp. 2, mixed breed ewes were assigned to receive an intravenous injection on day 5 after mating of either saline, LPS, recombinant human tumor necrosis factor (TNF)-α or LPS after pretreatment with dexamethasone. Pregnancy was diagnosed ultrasonographically on d 25, and live births were recorded at parturition. Challenge with LPS induced acute phase responses (fever, mucosal responses, lethargy and increased serum TNF, haptoglobin and serum amyloid A) and decreased pregnancy rates. Predictably, flunixin meglumine attenuated fever but did not increase pregnancy rate in LPS-treated ewes. Similarly, exogenous TNF alone induced mucosal and serum amyloid A responses but did not affect pregnancy. Pre-treatment with dexamethasone blocked fever and mucosal and lethargic responses and attenuated increases in TNF and haptoglobin but did not ameliorate LPS-induced pregnancy loss. In summary, acute challenge with LPS mimics bacterial-induced pregnancy losses in early pregnant ewes. Although pretreatment with dexamethasone decreased clinical signs and some innate immune responses, neither it nor flunixin meglumine prevented LPS-induced pregnancy loss. That exogenous TNF alone did not promote pregnancy loss indicates that other cytokines also contribute to LPS-induced embryonic loss.

Medicaments and oral healthcare 5. Adverse effects of -medications and over-the-counter drugs on teeth

Intrinsic tooth discoloration may occur as an adverse effect of fluoride and tetracyclines. Extrinsic tooth discoloration may occur as superficial staining or as discoloration of the superficial pellicle and/or biofilm due to chlorhexidine, liquid iron salts, essential oils, some antibiotics and stannous fluoride. Inhibition of orthodontic tooth movement has been reported due to the use of prostaglandin synthetase inhibitors. If medications or over-the-counter drugs induce hyposalivation or contain much sucrose, caries may develop. Erosion may occur if the acidity of medications or over-the-counter drugs is excessive. Attrition is a well-known adverse effect of serotonin reuptake inhibitors, antiparkinson agents, and antipsychotics. Congenital dysplasia is observed following childhood treatment with cytostatic drugs. External cervical root resorption is an adverse effect of internal teeth-whitening products. Prenatal exposure to antiepileptic drugs and childhood treatment with cytostatic drugs may cause dental agenesis. Antiseptic drugs applied for external teeth-whitening and toothpastes with additional ingredients to prevent extrinsic discoloration and creation of calculus, may cause tooth hypersensitivity.

Expert consensus for the diagnosis and treatment of patients with Gitelman syndrome

Gitelman syndrome (GS) is an autosomal recessive, salt-losing tubulopathy caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. GS is one of the most common inherited renal tubulopathy with a prevalence estimated at about one to ten per 40 000 people. The prevalence of GS is even higher in Asia than other countries. The majority of GS patients present mild and nonspecific symptoms during adolescence or adulthood. Common clinical manifestations are associated with electrolyte abnormalities, such as muscle weakness, salt craving and tetany. However, the phenotype of GS is highly variable and links to the quality of life. Diagnosis of GS is based on the clinical symptoms, biochemical abnormalities (normal/low blood pressure, metabolic alkalosis, hypomagnesemia, hypocalciuria and increased activity of renin-angiotensin- aldosterone system) and genetic test. Genetic diagnosis of GS is recommended for all patients and the diagnosis is confirmed when biallelic inactivating SLC12A3 mutations are identified. The differential diagnosis includes renal tubular acidosis, primary hyperaldosteronism, Bartter syndrome, Liddle syndrome and other diseases that cause hypokalemia. Among them Bartter syndrome (especially type Ⅲ) is the most important genetic disorder to consider due to its similar manifestations with GS. All GS patients are encouraged to keep high-sodium diet. Magnesium and potassium supplements (oral or intravenous) are usually given to GS patients to improve clinical symptoms. Other medicines such as aldosterone receptor antagonists, angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin Ⅱ receptor blockers (ARBs) and prostaglandin synthetase inhibitors (PGSIs) are alternative choices of treating hypokalemia, but the side-effects of these medication should be well considered. Management of GS includes health education, complication evaluation and regular follow-up. Annual evaluation by a nephrologist is recommended. Extra evaluation and treatment depend on special conditions, such as pregnancy, perioperative or growth period. Antenatal diagnosis for GS is technically feasible but not recommend due to the benign prognosis in the majority of patients. In general, this expert consensus statement aims to establish an initial framework for the better diagnosis, treatment and management of Chinese patients with GS.

Advance research of Acetaminophen treatment for symptomatic patent ductus arteriosus in pretermature infant

Due to the dysontogenesis of the arterial duct wall and the abnormal secretion of prostaglandin, symptomatic patent ductus arteriosus is thus often presented in preterm infants.In the past, Indomethacin or Ibuprofen (cyclooxygenase inhibitor) was always chosen to be the interventional medication.While in recent years, Acetaminophen (prostaglandin synthetase inhibitor) has become another therapeutic option for symptomatic patent ductus arteriosus with similar efficacy but less adverse events.The latest research of the mechanism, the therapeutic strategy of time, mode, dosage and duration, the efficacy and the adverse events of Acetaminophen were reviewed. Key words: Acetaminophen; Patent ductus arteriosus; Infant, pretermature

Efficacy of ormeloxifene in comparison to oral contraceptive pills in medical management of dysfunctional uterine bleeding

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Menstrual disorders are the most common gynecological condition resulting in hospital referrals. Dysfunctional Uterine Bleeding is an abnormal uterine bleeding, in the absence of any organic, systemic or iatrogenic cause. Among women in reproductive age, one in 20 consults her general practitioner each year with menorrhagia. This condition can be managed both medically and surgically. Pharmacological treatment options available for DUB are combined oral contraceptive pills, progestogens, danazol, gonadotrophin releasing hormone (GnRH) agonists, prostaglandin synthetase inhibitor, anti-fibrinolytics and ethamsylate. Role of ormeloxifene in dysfunctional uterine bleeding (DUB) is still in an exploring level.&lt;/span&gt;The purpose of the study was &lt;span lang="EN-IN"&gt;to evaluate the efficacy of ormeloxifene in the treatment of DUB and compare the effects of ormeloxifene with combined oral contraceptive pills for the control of DUB. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Sixty women presenting with DUB were randomly allocated to 2 equal groups, Group A were given ormeloxifene tablet @ 60 mg twice a week for 12 weeks, followed by 60 mg once a week for 12 weeks. Group B were given low dose combined oral contraceptive pills (OCP) containing 30 microgram ethinyloestradiol and 150 microgram levonorgestrel from day 1 to day 21st of the menstrual cycle for 6 cycles. The various parameters studied were reduction in menstrual blood loss which was measured by fall in pictorial blood loss assessment chart (PBAC) score, rise in haemoglobin (Hb) level and reduction in endometrial thickness, any drug side effects, compliance with the drug, dosage schedule and effect on quality of life after each month and at the end of trial period of 6 months. Patient’s level of satisfaction was assessed by improvement in Hb concentration, sense of wellbeing as well as overall general health, quality of life, sexual life and comfort with the continuation of the same drug.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Mean blood loss (PBAC score) following treatment showed significant reduction in both the groups, however this reduction was comparatively high in ormeloxifene treated group. The various parameters to assess the subjective and clinical improvement at the end 3 and 6 months post treatment showed significant improvement in both the treatment groups; however ormeloxifene group showed significantly better improvement in comparison to OCP group. Mean endometrial thickness also showed reduction in both the groups but more significant reduction was observed in ormeloxifene group as compared to OCP group following 6 months of treatment. Symptomatic relief and subjective feelings in relation to improvement of menstrual abnormalities, any undesirable side effects, about dosage compliance and any thought of discontinuing the drug by the patients indicated excellent control of menorrhagia in both the study group, which accounted for 86.66% in ormeloxifene group and 80% of individuals in OCP group. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; ORM is effective in control of DUB and can be used as an alternative to OCP for treatment of DUB with possibly minimal side effects and better dosage compliance.&lt;/p&gt;

Recent Update on Tocolytics for the Management of Preterm Labour

Tocolysis is the relaxation of the pregnant uterus to postpone delivery. Tocolytics are a wide variety of agents used to suppress uterine contraction given when delivery would result in preterm birth. Preterm birth the most important single determinant of adverse outcome in terms of both survival and quality of life of baby. Although preterm birth is defined as being before 37 completed weeks most mortality and morbidity is experienced by babies born before 34 weeks. Prevention and treatment of preterm birth is important though it is not possible when labour is too advanced, cervix is dilated for more than 4 cm and prolongation of pregnancy is hazardous because of intrauterine infection, placental abruption, IUGR, lethal congenital anomaly, severe PIH, eclampsia, active vaginal bleeding or cardiac disease 1,2. The aim of this paper is to review available data about the tocolytics. The tocolytic therapy also helpful for getting time for the administration of dexamethasone/betamethasone, a glucocorticoid drug which greatly accelerates fetal lung maturity. There is no clear first line tocolytic agent 3,4. Various types of drugs are used, with varying success rates and side effects that includes calcium-channel blockers, ? adrenergic receptor agonists, magnesium sulphate, prostaglandin-synthetase inhibitors, oxytocin receptor antagonists. Their specific effects on myometrial contractility, their safety, their efficiency, doses, route of entry, and side effects profile for the mother and the fetus are presented. The main question which tocolytic should be administrated is discussed.Bangladesh J Obstet Gynaecol, 2012; Vol. 27(1) : 21-26

Abnormal Uterine Bleeding: American College of Nurse-Midwives.

Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach.