Prolactin level in umbilical cord blood of newborn and its relation to respiratory distress syndrome

Background: Production of lower concentrations of prolactin in fetus is considered as one of the major contributor for the development of respiratory distress syndrome (RDS) in newborns considerably in pregnants with maternal complications. Hence the present study was conducted with the objective to measure the serum level of cord blood prolactin in normal pregnancy and in pregnancy with maternal complications and its association with development of RDS in newborn.Methods: In this prospective study of 100 women, 28 with normal pregnancy (Group A) and 72 with abnormal pregnancies (Group B) were included in the study. Umbilical cord blood was collected and serum prolactin level was estimated using radio-immuno assay. The obtained values were correlated with prevalence of RDS in neonates and maternal complications.Results: The average age of pregnant women participated in Group A was 26 years and Group B was 27 years. In Group A 2 babies with birth weight of 2001-3000 gm had a cord serum prolactin level of 216±137.8 ng/mL developed RDS. In Group B the level of prolactin was 285±276 and 326±132 ng/mL in 4 RDS babies with birth weight of <1000 gm and 1000-2000 gm respectively. It was observed that cord serum prolactin levels had no correlation with the mode of delivery, sex of newborn, steroid therapy. In Group A, 2 neonates developed RDS which were of gestational age between 32-35 weeks with mean prolactin level of 216 ng/ml, while in Group B, 1 neonate with gestational age less than 32 weeks and mean prolactin level of 480 and 4 neonates of 32-35 weeks with mean prolactin level of 266 ng/mL developed RDS. Out of 27 mothers with complications of PIH, 3 developed RDS. 1 case each from IUGR and twins developed RDS respectively.Conclusions: The risk of RDS is less in newborn with high prolactin level than in newborns with low prolactin levels. So prolactin might have a role in fetal lung maturation

Optimal sequence of hole-making operations using particle swarm optimization and modified shuffled frog leaping algorithm

Tool travel and tool switch scheduling are two major issues in hole-making operations. It is necessary to find the optimal sequence of operations to reduce the total processing cost of hole-making operations. In this work therefore, an attempt is made to use both a recently developed particle swarm optimisation algorithm and a shuffled frog leaping algorithm demonstrating in this way an example of plastic injection mould. The exact value of the minimum total processing cost is obtained by considering all possible combinations of sequences. The results obtained using particle swarm optimisation and shuffled frog leaping algorithm are compared with the minimum total processing cost results obtained by considering all possible combinations of sequences. It is observed that the results obtained using particle swarm optimisation and shuffled frog leaping algorithm are closer to the results of the minimum total processing cost obtained by considering all possible combinations of sequences presented in this work. This clearly shows that particle swarm optimisation and shuffled frog leaping algorithm can be effectively used in optimisation of large scale injection mould hole-making operations

MUCOADHESIVE MICROSPHERES: AN EMINENT ROLE IN CONTROLLED DRUG DELIVERY

ABSTRACT Mucoadhesion is simply known as interfacial force interactions between polymeric materials and mucosal tissues. In the last two decades mucoadhesive microspheres have received considerable attention for design of novel drug delivery systems due to their ability to prolong the residence time of dosage forms and to enhance drug bioavailability. Mucoadhesive microspheres have advantages like efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio, a much more intimate contact with the mucus layer, controlled and sustained release of drug from dosage form and specific targeting of drugs to the absorption site. Microspheres are the carrier linked drug delivery system in which particle size is ranges from 1-1000 μm range in diameter having a core of drug and entirely outer layers of polymer as coating material. Keywords: mucoadhesion, microspheres, controlled release, residence time. INTRODUCTION Since many years several kinds of diseases that may be acute or chronic diseases can be treated by using pharmaceutical dosage form like solutions, tablets, capsules, syrups, suspension, emulsion, ointments, creams, gels which can be used as orally, topically, or intravascular route. To get the proper therapeutic effect of these pharmaceutical dosage forms they should be administered several times a day, this results consequently undesirable toxicity, fluctuation in drug level and poor efficiency or therapeutic effect. Controlled release dosage form plays eminent role to overcome the problems which are discussed above. The most important example of controlled drug delivery system is mucoadhesive microspheres which can improve the therapeutic effect of administered drug. Also bioavailability of drug is also better than other conventional system because mucoadhesive microspheres remain close to the mucous membrane and absorption tissue. Drug delivery systems (DDS) that can precisely control the release rates or target drugs to a specific body site have had an enormous impact on the healthcare system. The last two and developing novel delivery systems referred to as &quot;mucoadhesive microspheres&quot;. [1] Physiology of mucin Mucus is produced in the eye, ear, nose and mouth. It also lines the respiratory, gastrointestinal and reproductive tracts. Its primary functions are the protection and lubrication of the underlying epithelium. Human cervical mucus, for instance, plays an integral role in both conception and contraception. It is essential to understand the structure and physical chemistry of mucus if the latter is to be exploited as a site for bioadhesive controlled drug release. Since the gastrointestinal tract is the primary site for drug absorption, the physiology of this site will be the focus of this discussion. The gelling properties which are essential to the function of mucus are the direct result of the glycoprotein present in the mucosal secretion. This glycoprotein is generally the same for various secretion sites within the body; however, specific and subtle biochemical differences have been identified. Mucus may be either constantly or intermittently secreted. The amount of mucus secreted also varies. The glycoproteinic component of mucus is a high molecular weight, highly glycosylated macromolecular system. This polydisperse natural polymer makes up between 0.5 and 5% of the fully hydrated mucus secretion. [10] The size of the intact molecule is approximately 1.8 x 10 6 , but the molecular weight of undegraded gastric mucin is as high as 4.5 x 10 7 . These macromolecules are highly expanded random coils made up of monomeric glycoproteins which for humans range from 5.5 x 1o 5 in the stomach to 2.4 x lo 5 in the small intestine. Oligosaccharide branches are attached to 63% of the protein core while the remainder of There are 34 disulphide bridges per molecule of rat goblet cell mucin, which has a molecular weight of 2 x 10 6 , while porcine intestinal mucin has 28 bridges per molecule. Human mucin has a similar density of disulphide bonds. The protein spine of the macromolecule has about 800 amino acid residues. Sugar chains are attached at about every three residues along the glycosylated regions; this results in approximately 200 side chains per molecule. This molecule is resistant to proteolytic attack in the glycosylated regions only. Thus, charge interactions may have a significant effect on the behaviour of mucus glycoproteins. The mucous gel covering the epithelium varies in thickness. In the human stomach, the mean thickness is 192 pm, while in the duodenum the thickness ranges from 10 to 400 pm In the gastrointestinal tract, mucus facilitates the passage of food and boluses through the alimentary canal. It also helps shield the epithelium from shear forces induced by peristaltic waves, and resists auto digestion. These functions are promoted by the constant secretion of mucus to replenish losses from turbulence and degradation. In response to an irritant, the amount of acidic side chains in the glycoprotein increases from 50 to 80%, making the macromolecule more negatively charged. The submucosal gland layer increases in depth and the number of goblet cells increases. The total content of non dialysable solids and pH also increase. In the GI tract, DNA and albumin thicken mucus in the diseased state. Mucosal irritation, such as exposure to alcohol or bile salts, elicits accelerated mucin release. Disease can significantly alter the nature and thickness of the mucus. This may lead to a change in the behaviour of the delivery system. Any drug delivery system which is intended to adhere to the mucus epithelium will need to adapt to a substrate which varies in depth and consistency, and may also change biochemically. Hypersecretion, which is more common than hyposecretion during disease, increases the transit rate through the GI tract, and thus reduces the residence time of a mucoadhesive device. Thus, it is essential to consider the physiology of the system when optimizing the formulation of an adhesive controlled release device. CLASSIFICATION OF MUCOADHESIVE POLYMERS Mucoadhesion is defined as interfacial force interactions between polymeric materials and mucosal tissues. In the last two decades mucoadhesive polymers have received considerable attention for design of novel drug delivery systems due to their ability to prolong the residence time of dosage forms and to enhance drug bioavailability. Various administration routes, such as ocular, nasal, gastrointestinal, vaginal and rectal, make mucoadhesive drug delivery systems attractive and flexible in dosage forms development. Mucoadhesive polymers can be classified as,- I. Traditional non-specific first-generation mucoadhesive polymers First-generation mucoadhesive polymers may be divided into three main subsets, namely: (1) Anionic polymers:-Anionic polymers are widely employed for its greatest mucoadhesive strength and low toxicity. These polymers are characterised by the presence of sulphate and carboxyl group that gives rise to net negative charge at PH values exceeding the pka of polymer. Example:-polyacrylic acid (PAA) &amp; its weakly cross linked derivatives, Sodium carboxymethyl cellulose (NACMC) [30] (2) Cationic polymers: -The most conveniently and widely used cationic polymer is chitosan which is produced by deacetylation of chitin. Chitin is a natural polysaccharide found predominantly in the shells of crustaceans such as crabs and shrimp, the cuticles of insects, and the cell walls of fungi. It is one of the most abundant biopolymers next to cellulose Most of the naturally occurring polysaccharides, e.g. cellulose, dextran, pectin, alginic acid, agar, agarose and carrageenans, are neutral or acidic in nature, whereas chitin and chitosan are examples of highly basic polysaccharides. The unique properties include II.Novel second-generation mucoadhesive polymers: The major disadvantage in using traditional nonspecific mucoadhesive systems (first generation) is that adhesion may occur at sites other than those intended. Unlike first-generation non-specific platforms, certain second-generation polymer platforms are less susceptible to mucus turnover rates, with some species binding directly to mucosal surfaces; more accurately termed &apos;&apos;cytoadhesives&quot;. Furthermore as surface carbohydrate and protein composition at potential target sites vary regionally, more accurate drug delivery may be achievable. MUCOADHESION Due its relative complexity, it is likely that the process of mucoadhesion cannot be described by just one of these theories. In considering the mechanism of mucoadhesion, a whole range &apos;scenarios&apos; for in-vivo mucoadhesive bond formation are possible. These include: A). Dry or partially hydrated dosage forms contacting surfaces with substantial mucus layers (typically particulates administered into the nasal cavity). B). fully hydrated dosage forms contacting surfaces with substantial mucus layers (typically particulates of many &apos;First Generation&apos;mucoadhesives that have hydrated in the luminal contents on delivery to the lower gastrointestinal tract). C). Dry or partially hydrated dosage forms contacting surfaces with thin/discontinuous mucus layers (typically tablets or patches in the oral cavity or vagina). D). fully hydrated dosage forms contacting surfaces with thin/discontinuous mucus layers (typically aqueous semisolids or liquids administered into the oesophagus or eye). It is unlikely that the mucoadhesive process will be the same in each case. In the study of adhesion generally, two steps in the adhesive process have been identified Step 2 -Consolidation stage: Various physicochemical interactions occur to consolidate and strengthen the adhesive joint, leading to prolonged adhesion. THEORIES ON MUCOADHESION [4, 5] Various kinds of theories are there which can explain the mechanism of mucoadhesion they are discussed below, TYPES OF MICROSPHERES Mucoadhesive microspheres:-Adhesion can be defined as sticking of drug to the membrane by using the sticking property of the water soluble polymers. Adhesion of drug delivery device to the mucosal membrane such as buccal, ocular, rectal, nasal etc can be termed as bio -adhesion. These kinds of microspheres exhibit a prolonged residence time at the site of application and causes intimate contact with the absorption site and produces better therapeutic action. [26] Magnetic microspheres:-This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. The different type are, Therapeutic magnetic microspheres: Are used to deliver chemotherapeutic agent to liver tumour. Drugs like proteins and peptides can also be targeted through this system.6 Diagnostic microspheres: Can be used for imaging liver metastases and also can be used to distinguish bowel loops from other abdominal structures by forming nano size particles supramagnetic iron oxides. Floating microspheres:-In this type of microspheres the bulk density is less than the gastric fluid and so remains buoyant in stomach without affecting gastric emptying rate. The release rate of drug is slow at the desired rate, if the system is floating on gasteric content and increases gastric residence and increases fluctuation in plasma concentration

Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid β Pathogenicity

Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Aβ42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Aβ42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Aβ and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism

Finite Size Effects in Simulations of Protein Aggregation

It is becoming increasingly clear that the soluble protofibrillar species that proceed amyloid fibril formation are associated with a range of neurodegenerative disorders such as Alzheimer's and Parkinson diseases. Computer simulations of the processes that lead to the formation of these oligomeric species are starting to make significant contributions to our understanding of the determinants of protein aggregation. We simulate different systems at constant concentration but with a different number of peptides and we study the how the finite number of proteins affects the underlying free energy of the system and therefore the relative stability of the species involved in the process. If not taken into account, this finite size effect can undermine the validity of theoretical predictions regarding the relative stability of the species involved and the rates of conversion from one to the other. We discuss the reasons that give rise to this finite size effect form both a probabilistic and energy fluctuations point of view and also how this problem can be dealt by a finite size scaling analysis

Voice Control Robot Using Arduino Pick and Place Object

VvvvA rescue robot is a robot that has been designed for the purpose of aiding in most rescueworkforces.Inmostofcommoncircumstancesthatskillrescuerobotsaremining fortunes, urban ruins, and imprisoned situations and blasts. This robot will help us in thesesituationsbyhelpinghumans.Themajorobjectiveofthisprojectistocontrolthe robot by using voice commands and to use in disaster regions. It is aimed for theusers to control a pick and place device through voice commands. Here the user can control all the movements of robot through voice commands to remove the objects in disaster regions.Itusesamicrophonetoconvertthegivenvoicecommandstoelectricalsignals andthissignalisrecognizedusingvoicerecognizerbymeansofavoicesensor.Thissensor is known as the VR Module. It will produce an output which is used by a controller to produce a control output. This output will drive the motor, thus robotic action takes place. It consists of L293D IC which will as a driving mechanism of the pick and place robot. Also, it has servomotor that helps for movement of arms. The two micro servos areusedingrippingtheobjectsatadistance.TheVRmoduleisusedheretorecognize the voice and give the output to microcontroller. If the signal is same with that of the trainedsignalinkeypad,theservoswillworkaccordingtoit.A rescue robot is a robot that has been designed for the purpose of aiding in most rescueworkforces.Inmostofcommoncircumstancesthatskillrescuerobotsaremining fortunes, urban ruins, and imprisoned situations and blasts. This robot will help us in thesesituationsbyhelpinghumans.Themajorobjectiveofthisprojectistocontrolthe robot by using voice commands and to use in disaster regions. It is aimed for theusers to control a pick and place device through voice commands. Here the user can control all the movements of robot through voice commands to remove the objects in disaster regions.Itusesamicrophonetoconvertthegivenvoicecommandstoelectricalsignals andthissignalisrecognizedusingvoicerecognizerbymeansofavoicesensor.Thissensor is known as the VR Module. It will produce an output which is used by a controller to produce a control output. This output will drive the motor, thus robotic action takes place. It consists of L293D IC which will as a driving mechanism of the pick and place robot. Also, it has servomotor that helps for movement of arms. The two micro servos areusedingrippingtheobjectsatadistance.TheVRmoduleisusedheretorecognize the voice and give the output to microcontroller. If the signal is same with that of the trainedsignalinkeypad,theservoswillworkaccordingtoit.

Role of progenitor cell producing normal vagina by metaplasia in laparoscopic peritoneal vaginoplasty

Context: Host of vaginoplasty techniques have been described. None has been successful in developing normal vagina. Laparoscopic peritoneal vaginoplasty (LPV) is performed in Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) culminating in normal vagina. Aims: This study aims to confirm normal development of neovagina by anatomical and functional parameters of histology, cytology, and ultrasonography (USG) in LPV. To identify peritoneal progenitor cell by OCT4/SOX2 markers. To demonstrate the metaplastic conversion of peritoneum to neovagina and the progenitor cell concentration, distribution pattern. Settings and Design: This is prospective experimental study, conducted at teaching hospital and private hospital. Subjects and Methods: Fifteen women of MRKHS underwent LPV followed by histology, cytology, two-/three-dimensional USG of neovagina. Four women underwent peritoneal biopsy for identification of progenitor cells with OCT4/SOX2 markers. One patient underwent serial biopsies for 4 weeks for histology and progenitor cell immunohistochemistry. Results: Normal vaginal histology and cytology were apparent. USG of neovagina showed normal appearance and blood flow. Two peritoneal samples confirmed the presence of progenitor cells. Serial biopsies demonstrated the epithelial change from single to multilayer with stromal compaction and neoangiogenesis. The progenitor cells concentration and different distribution patterns were described using SOX2/OCT4 markers. Conclusions: We have shown successful peritoneal metaplastic conversion to normal vagina in LPV. The progenitor cell was identified in normal peritoneum using SOX2/OCT4 markers. The progenitor cell concentration and pattern were demonstrated at various stages of neovaginal development

Post Print Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity. Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid b Pathogenicity

Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Ab 42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Ab 42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Ab and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism