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Objective  The aim of the study is to obtain insights on the short and long-term safety and effectiveness of isoxsuprine hydrochloride as a tocolytic agent in the management of PTL. Study Design  In this prospective, single-center, noncomparative study, patients (with preterm labor at gestational age of 24–37 weeks) were administered intravenous (IV) infusion of 40-mg isoxsuprine hydrochloride until uterine quiescence, followed by intramuscular (IM) injection of isoxsuprine hydrochloride 10 mg/4-hourly for first 24 hours and maintained with retard 40-mg sustained release capsule (two times a day) till the time of delivery or 37 completed weeks of pregnancy. Results  All patients (n  = 50) achieved successful tocolysis in 24 hours and 48 hours postadministration of isoxsuprine hydrochloride (IV/IM/oral). Mean (±SD) gestation age at the time of delivery was 39.8 ± 2.1 weeks, with latency period of 58.5 ± 18.7 days. Pregnancy outcomes were normal in all the patients and no congenital anomaly/fetal infection was reported. Mean (±SD) fetal birth weight was 2.7 ± 0.3 kg; mean (±SD) Apgar score at 1 and 5 minutes were 7.5 ± 0.6 and 9.2 ± 0.4, respectively. Maternal tachycardia and vomiting (8.0% each) were the commonly reported adverse drug reactions, which were resolved with dose adjustment. Conclusion  Isoxsuprine was found to be an effective and well-tolerated tocolytic agent in arresting PTL, in turn resulting in the overall improvement in maternal and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Abstract A highly sensitive voltammetric sensor is prepared using multi-walled carbon nanotube decorated with silver nanoparticles (AgNPs-MWCNTs) and is applied for the determination of Isoxsuprine (ISOX). The characterization of the prepared nanocomposite is performed using energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), atomic force microscopy (AFM), transmission electron microscope (TEM), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry techniques. The electrochemical behavior of ISOX is studied on the surface of the modified electrode by linear sweep and cyclic voltammetry methods. Under the optimized conditions such as pH of the supporting electrolyte, accumulation time and amount of the casted modifier, a significant electrochemical improvement is observed toward the electro-oxidation of ISOX on the surface of AgNPs-MWCNTs glassy carbon electrode (AgNPs-MWCNTs/GCE), in comparison to MWCNTs/GCE and bare GCE. At the surface of the modified electrode two oxidation peaks are observed for ISOX at potentials around 0.63 V (peak I) and 0.82 V (peak II) in BR buffer solution of pH 7.0. By using two anodic peaks of ISOX, two linear dynamic ranges of 0.04–5.0 μmol L−1 and 0.2–5.0 μmol L−1 with detection limits of 12 nmol L−1 and 60 nmol L−1are obtained for peaks I and II, respectively. The modified electrode showed a simple fabrication procedure, high sensitivity, stability and good reproducibility in response to ISOX. The AgNPs-MWCNTs/GCE is successfully applied for the accurate determination of trace amounts of ISOX in pharmaceutical and clinical preparations. Highlights • Ag nanoparticles decorated on MWCNTs are for the surface modification of glassy carbon electrode. • The modified electrode is characterized by means of TEM, SEM, EDX, XRD, AFM and impedance techniques. • The electro-oxidation and determination of Isoxsuprine are thoroughly studied by the prepared modified electrode. • The electrode is applied for the accurate and sensitive determination of ISOX in pharmaceutical and clinical preparations. [ABSTRACT FROM AUTHOR]

Isoxsuprine hydrochloride (ISO) and levothyroxine (LEV) are medicines which can be utilized alone or simultaneously by pregnant women. The purpose of this work is to investigate the separate and simultaneous interaction of ISO and LEV with β-LG. The results showed that both drugs can bind to β-LG; the static quenching was suggested for fluorescence quenching mechanism of β-LG.The values of binding constants (K β-LG-ISO  = 2.69 × 10 4  M −1 , K β-LG-LEV  = 0.54 × 10 3  M −1 and K β-LG–ISO–LEV  = 2.18 × 10 3  M −1 at 310 K) suggested that ISO has stronger binding affinity toward β-LG than LEV and affinity of β-LG to LEV is increased in the presence of ISO while the presence of LEV has no significant effect on the affinity of protein to ISO. Thermodynamic parameters showed that the binding of LEV to β-LG are hydrogen bonding and Van der Waals forces but the formation of β-LG–ISO is hydrophobic associations. The results of FT-IR and UV–visible measurements indicated that the binding of both drugs to β-LG may induce conformational changes of protein. In silico molecular docking analyses confirmed that ISO and LEV binds to residues located at site I and site II of β-LG, respectively. [ABSTRACT FROM AUTHOR]

In the present work, the interaction of Isoxsuprine (ISX) with Calf thymus DNA (ct-DNA) under physiological conditions (Tris–HCl buffer of pH 7.4) was investigated by using electronic absorption, circular dichroism, viscosity, electrochemical studies, fluorescence techniques, salt effect studies and computational studies. Competitive fluorimetric studies with Hoechst 33258 have shown that ISX exhibit the ability to displace the DNA-bound Hoechst 33258, indicating that it binds to ct-DNA in strong competition with Hoechst 33258 for the minor groove binding. Furthermore, the resulting data showed that ISX cannot displace methylene blue or acridine orange, which are the common intercalator molecules. The viscosity of ct-DNA solution was almost unchanged on addition of ISX and circular dichroism (CD) spectra of ct-DNA showed small changes in the presence of ISX which is in agreement with groove binding mode of interaction. Thus all above studies showed that the ISX drug binds to ct-DNA in a groove binding mode.The salt-effect studies showed the non-electrostatic nature of binding of ISX to ct-DNA. Moreover, molecular docking results support the above experimental data and suggest that ISX prefers to bind on the minor groove of ct-DNA. [ABSTRACT FROM AUTHOR]

Premature labor is a cause of high rates of perinatal morbidity and mortality. The use of tocolytics is one of the efforts to handle the risk of preterm labor. Tocolytics which are widely used in Indonesia is isoxsuprine and nifedipine. The purpose of this study was to identify the difference of effectiveness and safety of isoxsuprine as tocolytics in the risk of preterm labor. This was an observational study in the form of a case study that was done in detail and depth to the patients who were diagnosed as imminent preterm labor. In conclusion, there were differences in the effectiveness and safety of isoxsuprine and nifedipine as tocolytics in the risk of preterm labor. [ABSTRACT FROM AUTHOR]

Four accurate, precise, and validated stability-indicating spectrophotometric methods handling either zero-order spectra or ratio spectra have been developed and compared for the analysis of isoxsuprine hydrochloride (ISX) in the presence of its oxidative degradation product. The first two methods processed zero-order spectra, namely graphical absorbance ratio or Q-Analysis and area under the curve, whereas the third and fourth methods manipulated ratio spectra, namely the ratio difference spectrophotometric method and derivative ratio. The proposed methods showed good linearity in the range of 2-23 µg/mL. The methods were tested for specificity using laboratory-prepared mixtures containing the drug and its degradation product. The proposed methods were applied for the determination of ISX in Vascular tablets and the obtained results were acceptable, with small percentage RSD values. The validity of the proposed procedures was further assessed by applying the standard addition technique, which showed no interference from excipients. The obtained results were statistically compared with those obtained by the reported method, showing no significant differences when t- and F-tests were applied. [ABSTRACT FROM AUTHOR]

Isoxsuprine hydrochloride (vasodilator drug), folic acid and ascorbic acid are medicines which can be utilized alone or simultaneously by pregnant women. In the present work the competitive binding of isoxsuprine hydrochloride (ISO) with human serum albumin (HSA) in the absence and presence of folic acid (FOL) and ascorbic acid (AS) was investigated using different spectroscopic probes and molecular docking studies. The results of fluorescence suggested that isoxsuprine alone or in the presence of ascorbic acid can bind to HSA and quench the fluorescence of HSA with static mechanism but For HSA–folic acid–isoxsuprine system, dynamic type of quenching mechanisms is involved. The values of binding constants (K HSA–ISO ~ 1.2 × 10 3 M − 1 , K HSA–AS–ISO ~ 2.1 × 10 3 M − 1 and K HSA–FOL–ISO ~ 0.7 × 10 3 M − 1 ) suggested that affinity of HSA to isoxsuprine increased in the presence of ascorbic acid while the presence of folic acid reduced the affinity of protein to isoxsuprine. The results of FT-IR and circular dichroism measurements indicated that the binding of isoxsuprine to HSA in the absence and the presence of folic acid and ascorbic acid may induce conformational and microenvironmental changes of protein. Not only do these types of spectroscopy techniques provide all the information about the systems, molecular docking, also emphasizes the results and is employed for the identification of the active site residues, bioactive conformer of Isoxsuprine and their critical interactions. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate the use of 35Cl solid-state NMR (SSNMR) at moderate (9.4 T) and high (21.1 T) magnetic field strengths for the structural fingerprinting of hydrochloride (HCl) salts of active pharmaceutical ingredients (APIs) and several polymorphs, in both bulk and dosage forms. These include salts of metformin, diphenhydramine, nicardipine, isoxsuprine and mexiletine (the crystal structure of a mexiletine polymorph is reported herein). Signal-enhancing pulse sequences utilizing frequency-swept pulses and broadband cross polarization were employed to significantly decrease experimental times. In most cases, powder X-ray diffraction (pXRD) patterns and 13C SSNMR spectra are not useful for characterizing the APIs in dosage forms, due to interfering signals from the excipients (e.g., fillers and binders). However, it is demonstrated that 35Cl SSNMR can be used independently to fingerprint individual APIs and to detect the nature of the solid phases in the dosage forms without interference from the excipient. 35Cl SSNMR experiments were also conducted on systems with multiple polymorphs (i.e., isoxsuprine HCl and mexiletine HCl), and the solid phases of these APIs in their dosage forms are identified. 35Cl EFG tensors obtained from plane-wave DFT calculations on model systems are also presented and discussed in the context of their relationship to the local hydrogen-bonding environments of the chloride ions. This methodology shows great promise for identification of solid phases and detection of polymorphs and impurities, which are matters of importance for quality assurance in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The massive increase in size of the fetus and uterus in the last trimester is accompanied by an increasing demand for nutrients and oxygen, and it is assumed that this demand is met by increasing uterine and fetal perfusion. The goals of this study were to measure the perfusion of the uterine arteries and the placentomes in the last month of gestation and to investigate the effect of epidural anesthesia and isoxsuprine on perfusion. During the last month of gestation, eight Braunvieh cows underwent nine color Doppler sonographic examinations of the uterine arteries to determine diameter (DM), pulse rate (PR), resistance index, time-averaged maximum blood flow velocity (TAMV), and blood flow volume (BFV), and power-mode Doppler sonography was used to determine perfusion of placentomes. The PR increased (P < 0.001), and the BFV and TAMV of the ipsilateral uterine artery decreased between 4.5 and 0.5 weeks prepartum (BFV, 236.8 ± 65.80 and 208 ± 41.52 cm 3 /s, P < 0.01; TAMV, 140.0 ± 26.53 cm/s and 125.2 ± 18.46 cm/s, P < 0.05). After sonographic examination, the cows received epidural administration of local anesthetic (100-mg lidocaine) in the sacrococcygeal space or isoxsuprine (200 mg/cow, iv), and the sonographic measurements were repeated 30 minutes later. After epidural anesthesia, the TAMV and BFV of the contralateral uterine artery increased by 5.4% (P < 0.05) and 7.9% (P < 0.01). In the placentomes of the gravid uterine horn, the relative placentome perfusion and the color pixel grading (Cp) increased by 10.1% (P < 0.05) and 11.5% (P < 0.01) after epidural anesthesia. After isoxsuprine, the DM, PR, and BFV increased by 4.7%, 49.3%, and 16.9% in the ipsilateral uterine artery and by 10.8%, 48.7%, and 22.8%, respectively in the contralateral uterine artery. The TAMV of the ipsilateral uterine artery increased by 7.1% (P < 0.01), and the resistance index decreased in both uterine arteries (ipsilateral 24.2%, contralateral 14.9%, both P < 0.00001). Isoxsuprine increased the relative placentome perfusion and the Cp of the placentomes by 18.1% and 18.3% in the gravid horn and by 10.2% and 24.2% in the nongravid horn. Blood flow variables changed little in the last month of gestation. However, epidural anesthesia and isoxsuprine caused changes in uterine and placentome perfusion that suggest improvement of placental nutrient and oxygen supply to the fetus. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period.Methods: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8).Results: The median gestational age at diagnosis was 34 weeks (range, 27-38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes.Conclusions: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients. [ABSTRACT FROM AUTHOR]

Background: Isoxsuprine (Vasodilan) is a beta-adrenergic that directly affects the vascular smooth muscle and results in peripheral vascular dilation. Isoxsuprine relaxes the uterine smooth muscles and is used for treatment of pre-term labor and dysmenorrhea. Isoxsuprine is used extensively in hospitals and private clinics in Iran; however, few studies have reported its safety and efficacy in the prevention of pre-term labor. Objective: The aim of this study was to assess the effect of maintenance therapy with oral isoxsuprine for the prevention of pre-term labor. Methods: We undertook a blinded prospective randomized trial of 70 women with singleton pregnancies who presented in pre-term labor between 26 to 34 weeks of gestation. After arresting the contractions with intravenous magnesium sulfate, the patients were randomized into two groups, with the treatment group receiving oral isoxsuprine until 34 weeks of gestation. Response to treatment was assessed by the progression of the pregnancies in both groups. The data were analyzed using SPSS software. Results: Our results showed that 14 (40%) of the patients in the case group and 12 (34.29%) of patients in the control group had pre-term births, and there was no significant difference between the two groups (P=0.621). Also four women (11.43%) in the case group and five women (14.29%) in the control group delivered before 34 weeks (P=0.721). Conclusion: Oral isoxsuprine was not effective as a maintenance treatment in preventing pre-term births or in delaying delivery until after 34 weeks. Larger studies are needed to identify the best treatment for pre-term labor. [ABSTRACT FROM AUTHOR]

Isoxsuprine HCl-loaded microbeads using sodium alginate (SA)-carboxymethyl cashew gum (CMCG) polymer-blends were developed through ionotropic-gelation technique using ZnSO 4 as cross-linker. Effects of polymer-blend ratio and cross-linker concentration on drug encapsulation efficiency (DEE) and cumulative drug release at 7 h ( R 7h ) were optimized by 3 2 factorial design. Optimized microbeads were of excellent combination of high DEE (79.92 ± 2.51%) and suitable sustained drug release pattern over a prolonged period of 7 h (58.67 ± 2.26%). The microbead surface morphology was analyzed by SEM. The physical state of isoxsuprine HCl within the optimized microbead matrix was analyzed by FTIR and DSC. In vitro isoxsuprine HCl release from alginate-CMCG microbeads in phosphate buffer (pH, 6.8) showed prolonged sustained drug release and Korsmeyer-Peppas model ( R 2 = 0.9959–0.9992) over 7 h. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability and treatment options are limited. A promising approach to accelerate the development of new therapeutics is the use of high-throughput screening of chemical libraries. Using a cell-based high-throughput oxygen-glucose deprivation (OGD) model, we evaluated 1,200 small molecules for repurposed application in stroke therapy. Isoxsuprine hydrochloride was identified as a potent neuroprotective compound in primary neurons exposed to OGD. Isoxsuprine, a β2-adrenergic agonist and NR2B subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonist, demonstrated no loss of efficacy when administered up to an hour after reoxygenation in an in vitro stroke model. In an animal model of transient focal ischemia, isoxsuprine significantly reduced infarct volume compared to vehicle (137±18 mm3 versus 279±25 mm3, p<0.001). Isoxsuprine, a peripheral vasodilator, was FDA approved for the treatment of cerebrovascular insufficiency and peripheral vascular disease. Our demonstration of the significant and novel neuroprotective action of isoxsuprine hydrochloride in an in vivo stroke model and its history of human use suggest that isoxsuprine may be an ideal candidate for further investigation as a potential stroke therapeutic. [ABSTRACT FROM AUTHOR]

Abstract: The maternal portion of the bovine placenta receives blood mainly from the uterine arteries (AUT) and the fetal portion from the umbilical arteries (AUM). Placental perfusion is crucial for fetal development and undergoes adaptive changes during pregnancy according to the fetal requirements. One goal of this study was to investigate changes in Doppler sonographic measurements of blood vessels that supply blood to the placenta in cows during the last 4 weeks of pregnancy. Another goal was to examine how these measurements are affected by three drugs commonly used in cows at the time of parturition. Nine cows underwent Doppler sonographic examination of the AUT ipsilateral and contralateral to the pregnant horn and one AUM three times per week during the last 4 weeks of gestation. This was followed by the randomized administration of one of the three following experimental drugs per day: isoxsuprine (200 mg/cow, iv), xylazine (2 mg/100 kg, iv), and lidocaine for epidural anesthesia (100 mg/cow). Doppler sonographic examination was repeated 30 minutes after medication. Maternal pulse rate increased during the study period (P < 0.001), and the diameter of the contralateral AUT was smaller in the last week before birth than in the two preceding weeks. The resistance index (RI) of the ipsilateral AUT was smaller in the last week than in the first 2 weeks of the study period. Uterine blood flow volume increased after isoxsuprine by 5% and after epidural anesthesia by 6% (both P ≤ 0.05) and decreased after xylazine by 10% (P < 0.001). Isoxsuprine was the only drug that elevated the blood flow volume in the AUM (P ≤ 0.05). Xylazine increased the RI of both AUT (both P < 0.001) and significantly reduced maternal and fetal pulse frequencies, whereas isoxsuprine significantly reduced the RI of both AUT and the AUM and increased maternal and fetal pulse frequencies. The results reported that Doppler sonographic measurements of uterine and AUM change little in the last month of pregnancy in the cow. Isoxsuprine and epidural anesthesia with lidocaine have the potential to improve uterine perfusion. [Copyright &y& Elsevier]

Objectives: The aim of the study was to compare the effectiveness of vasodilator isoxsuprine to dexamethasone with hyaluronidase injections and physiotherapy in the treatment of oral submucous fibrosis. Materials and methods: Forty patients with oral submucous fibrosis were randomly assigned into three groups. Group A patients ( n = 15) received 10 mg isoxsuprine tablets four times per day, group B ( n = 15) biweekly dexamethasone with hyaluronidase intralesional injections, and group C ( n = 10) placebo tablets. In addition, all patients were instructed physiotherapy exercises. The treatment time was 6 weeks and patients were followed-up for 4 months thereafter. The effect of the treatment was evaluated by measurements of inter-incisal distance and oral burning sensation and evaluation of histological findings of the diseased mucosa. Results: Mouth opening increased and burning sensation decreased significantly in all groups, but the effects were significantly greater in groups receiving either oral isoxsuprine or dexamethasone with hyaluronidase injections in addition to physiotherapy. The decrease in burning sensation occurred more rapidly in patients receiving intralesional dexamethasone with hyaluronidase. Histological improvement was not observed in any of the groups. Conclusions: Oral isoxsuprine as well as dexamethasone with hyaluronidase injections combined to physiotherapy alleviate symptoms of oral submucous fibrosis significantly more efficiently than physiotherapy alone. Clinical relevance: Oral isoxsuprine can be considered as a new candidate drug for the treatment of oral submucous fibrosis. Physiotherapy exercises provide relief of symptoms and should be instructed to all patients. [ABSTRACT FROM AUTHOR]

Abstract: A new analysis method using ultra-performance liquid chromatography (UPLC)–quadrupole-time-of-flight mass spectrometry (Q/TOF MS) was developed for screening and confirmation of 12 β-agonists in feeds. Under the optimized gradient elution conditions, it takes only 6min to separate all 12 β-agonists, and the critical pair of Ractopamine and Isoxsuprine isomers was almost completely separated. Based on the over 10,000 full-width at half maximum (FWHM) mass resolution and high mass accuracy features of TOF MS with 20mDa mass window, accurate mass chromatograms were reconstructed for individual compounds. The fragmentation pathways of 12 β-agonists were also studied using Q-TOF MS. The potential of UPLC–Q/TOF MS for confirmatory analysis was shown by determining the accurate mass of all compounds and fragment ions upon collision-induced-dissociation (CID) at different energies. The extra mass measurement errors for all β-agonists were found to be within 5ppm. The limits of detection (LODs) and limits of quantitation (LOQs) were determined for all β-agonists in feeds and found to be 1–5ng/mL and 5–50μg/kg, respectively. The method of UPLC–Q/TOF MS developed in this study was initially applied to the research of feeds for analysis of 12 β-agonists and proved to be accurate, sensitive, convenient and practical. [Copyright &y& Elsevier]

Background:As metastasis is the prime cause of death from malignancies, there is vibrant interest to discover options for the management of the different mechanistic steps of tumour spreading. Some approved pharmaceuticals exhibit activities against diseases they have not been developed for. In order to discover such activities that might attenuate lymph node metastasis, we investigated 225 drugs, which are approved by the US Food and Drug Administration.Methods:A three-dimensional cell co-culture assay was utilised measuring tumour cell-induced disintegrations of the lymphendothelial wall through which tumour emboli can intravasate as a limiting step in lymph node metastasis of ductal breast cancer. The disintegrated areas in the lymphendothelial cell (LEC) monolayers were induced by 12(S)-HETE, which is secreted by MCF-7 tumour cell spheroids, and are called 'circular chemorepellent induced defects' (CCIDs). The putative mechanisms by which active drugs prevented the formation of entry gates were investigated by western blotting, NF-κB activity assay and by the determination of 12(S)-HETE synthesis.Results:Acetohexamide, nifedipin, isoxsuprine and proadifen dose dependently inhibited the formation of CCIDs in LEC monolayers and inhibited markers of epithelial-to-mesenchymal-transition and migration. The migration of LECs is a prerequisite of CCID formation, and these drugs either repressed paxillin levels or the activities of myosin light chain 2, or myosin-binding subunit of myosin phosphatase. Isoxsuprine inhibited all three migration markers, and isoxsuprine and acetohexamide suppressed the synthesis of 12(S)-HETE, whereas proadifen and nifedipin inhibited NF-κB activation. Both the signalling pathways independently cause CCID formation.Conclusion:The targeting of different mechanisms was most likely the reason for synergistic effects of different drug combinations on the inhibition of CCID formation. Furthermore, the treatment with drug combinations allowed also a several-fold reduction in drug concentrations. These results encourage further screening of approved drugs and their in vivo testing. [ABSTRACT FROM AUTHOR]

Serial electrocardiograms (ECGs) were studied prospectively in 80 apparently healthy newborn infants; 30 infants exposed in utero to prolonged tocolytic therapy (21 to ritodrine and 9 to isoxsuprine) and 50 infants non-exposed in utero to drugs (control group) matched for gestational age, Apgar score, and birth weight. Duration of exposure to tocolysis was at least 30 days (30-180 days) with an oral dosage of 10 mg 3 times daily. ECGs were graded for changes suggestive of ischaemia using the arbitrary grading system described by Jedeikin et al. In all infants with ECG features of myocardial ischaemia, serum creatine-phosphokinase iso-enzyme (CK-MB) activity was measured. Six out of 21 infants to ritodrine and six out of nine infants exposed to isoxsuprine showed a degree of ECG ischaemia which persisted for several weeks. No control infant presented grade 2 or 3 ECG changes after the 5th day of life. The results of this study seem to show that prolonged tocolytic therapy with beta-sympathomimetics has side-effects on the fetal myocardium and suggest that this treatment be reserved only for selective cases and/or for short periods of time. [ABSTRACT FROM AUTHOR]

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H2S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H2S/KATP signaling pathways and blockade of α1-adrenoceptors and L-type voltage-dependent Ca2+ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H2S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

A pregnant Deccani ewe was presented with protrusion of mass through the vulva in sitting posture. On through clinico-gynaecological examination, it was found that the mass propeling out of vulval cleft was the cervix of a healthy gravid uterus. To avoid posterior straining, the animal was given epidural anesthesia in the first inter coccygeal space. The mass was lifted and urine was relieved by catheterization. The prolapsed mass was washed and cleaned with mild potassium permagnate solution and then applied with ice cubes. After reduction, lignocaine jelly was applied and the prolapsed mass was re-positioned. Purse string sutures were applied on the vulval lips to prevent the recurrence. The therapeutic management included inj. Calcium gluconate and inj. Isoxsuprine and supportive therapy for five days. The ewe made an uneventful recovery and normal delivery was observed. [ABSTRACT FROM AUTHOR]