How pregnancy can affect autoimmune diseases progression?

Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother’s circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.     

What Happened to <Emphasis Type="Italic">Nezara viridula</Emphasis> (L.) in the Americas? Possible Reasons to Explain Populations Decline

Once abundant in the Americas, the southern green stink bug Nezara viridula (L.) has gradually declined in numbers. Until the 1990s, it was considered the main pest of major crops such as soybean, Glycine max (L.) Merrill, particularly in southern Brazil and southern USA, as well as Argentina, Uruguay, and other countries. In the past 15+ years, a dramatic population decrease was observed to the point of now being considered a secondary pest in these referred countries. In this article, we list and discuss possible reasons which explain the decline in N. viridula population in the Americas. These factors include the following: (1) the steady increase of herbicides used in no-tillage/multiple cropping systems affecting potential hosts such as weeds in crop fields and nearby natural vegetation; (2) the change in cultivation systems, mostly in the Neotropics, favoring other species more adapted to exploit crops in modern day agriculture; (3) competition among several species of stink bugs that colonize major crops; (4) the growing impact of several species of egg parasitoids, some of them laboratory reared and released in crop fields, and other natural enemies (parasitoids and predators); and (5) the impact of global climate change affecting its distribution and biology.     

Detailed Morphology of All Life Stages of the Agave Red Worm, <Emphasis Type="Italic">Comadia redtenbacheri</Emphasis> (Hammerschmidt) (Lepidoptera: Cossidae)

The agave red worm, Comadia redtenbacheri (Hammerschmidt), is an important source of food and income in Mexico. Despite its importance, several aspects of its biology, morphology, and behavior remain poorly studied. In this work, we describe and illustrate the morphology of all the life stages that may aid in understanding certain aspects of its biology. To obtain all life stages, last instar larvae were collected from agave plants and allowed to pupate; after the adults emerged, they were allowed to mate and oviposit. The frenulum is longer in males; epiphysis I is longer in females than in males; the abdomen bears two types of tubercles of unknown function. Eggs present a reticulate chorion; primary rosette cells are highly variable in shape; the micropylar formula is (10-14): (12-13). First instar larvae are white, becoming red as they develop; L3 in the prothorax is subprimary; the SV setal group in A1 is comprised of only SV1 on first instar larvae; last instars have several secondary setae. Pupae are adecticous and obtect; there are rows of spines on the dorsum of the abdomen. The biological significance of some of the findings is discussed.     

Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes <Emphasis Type="Italic">Versus</Emphasis> Self-Nanoemulsifying Drug Delivery System

The objective of this study was to develop proliposomes and self-nanoemulsifying drug delivery system (SNEDDS) for a poorly bioavailable drug, valsartan, and to compare their in vivo pharmacokinetics. Proliposomes were prepared by thin-film hydration method using different lipids such as soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoyl phosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. SNEDDS formulations were prepared using varying concentrations of capmul MCM, labrafil M 2125, and Tween 80. Both proliposomes and SNEDDS were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water and 0.1 N HCl using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal permeation techniques. Among the formulations, the proliposomes with drug/DMPG/cholesterol in the ratio of 1:1:0.5 and SNEDDS with capmul MCM (16.0% w/w), labrafil M 2125 (64.0% w/w), and Tween 80 (18.0% w/w) showed the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SNEDDS as compared to pure valsartan. Valsartan permeability across PAMPA and everted rat intestinal permeation models was significantly higher with proliposomes and SNEDDS. Following single oral administration of proliposomes and SNEDDS, a relative bioavailability of 202.36 and 196.87%, respectively, was achieved compared to pure valsartan suspension. The study results indicated that both proliposomes and SNEDDS formulations are comparable in improving the oral bioavailability of valsartan.     

Gastroretentive Matrix Tablets of Boswellia Oleogum Resin: Preparation,Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation,and Cytoprotective Effect on Indomethacin-Induced Gastric Ulcer in Rabbits

Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets.     

Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL^TM T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.     

Stage 2 Process Performance Qualification (PPQ): a Scientific Approach to Determine the Number of PPQ Batches

The approach documented in this article reviews data from earlier process validation lifecycle stages with a described statistical model to provide the “best estimate” on the number of process performance qualification (PPQ) batches that should generate sufficient information to make a scientific and risk-based decision on product robustness. This approach is based upon estimation of a statistical confidence from the current product knowledge (Stage 1), historical variability for similar products/processes (batch-to-batch), and label claim specifications such as strength. The analysis is to determine the confidence level with the measurements of the product quality attributes and to compare them with the specifications. The projected minimum number of PPQ batches required will vary depending on the product, process understanding, and attributes, which are critical input parameters for the current statistical model. This new approach considers the critical finished product CQAs (assay, dissolution, and content uniformity), primarily because assay/content uniformity and dissolution as well as strength are the components of the label claim. The key CQAs determine the number of PPQ batches. This approach will ensure that sufficient scientific data is generated to demonstrate process robustness as desired by the 2011 FDA guidance.     

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

In order to regulate the skin permeation rate (flux) of escitalopram (ESP), ion-pair strategy was used in our work. Five organic acids with different physicochemical properties, benzoic acid (BA), ibuprofen (IB), salicylic acid (SA), benzenesulfonic acid (BSA), and p-aminobenzoic acid (PABA), were employed as counter-ions to regulate the permeation rate of ESP across the rabbit abdominal skin in vitro. The interaction between ESP and organic acids was characterized by FTIR and ¹³C NMR spectroscopy. Results showed that all organic acids investigated in this study performed a controlling effect on ESP flux. To further analyze the factors concerned with the permeation capability of ESP-acid complex, a multiple linear regression model was used. It is concluded that the steady-state flux (J) of ESP-acid complexes had a positive correlation with log K _o/w (the n-octanol/water partition coefficient of ion-pair complex) and pK _a (the acidity of organic acid counter-ion), but a negative correlation with MW (the molecular weight of ion-pair complex). The logK _o/w of ion-pair complex is the primary one in all the factors that influence the skin permeation rate of ESP. The results demonstrated that organic acid with appropriate physicochemical properties can be considered as suitable candidate for the transdermal drug delivery of escitalopram.     

Fusion Method for Solubility and Dissolution Rate Enhancement of Ibuprofen Using Block Copolymer Poloxamer 407

Aim of current research was to prepare ibuprofen-poloxamer 407 binary mixtures using fusion method and characterize them for their physicochemical and performance properties. Binary mixtures of ibuprofen and poloxamer were prepared in three different ratios (1:0.25, 1:0.5, and 1:0.75, respectively) using a water-jacketed high shear mixer. In vitro dissolution and saturation solubility studies were carried out for the drug, physical mixtures, and formulations for all ratios in de-ionized water, 0.1 N HCl (pH?=?1.2), and phosphate buffer (pH?=?7.2). Thermal and physical characterization of samples was done using modulated differential scanning calorimetry (mDSC), X-ray powder diffraction (XRD), and infrared spectroscopy (FTIR). Flow properties were evaluated using a powder rheometer. Maximum solubility enhancement was seen in acidic media for fused formulations where the ratio 1:0.75 had 18-fold increase. In vitro dissolution studies showed dissolution rate enhancement for physical mixtures and the formulations in all three media. The most pronounced effect was seen for formulation (1:0.75) in acidic media where the cumulative drug release was 58.27% while for drug, it was 3.67%. Model independent statistical methods and ANOVA based methods were used to check the significance of difference in the dissolution profiles. Thermograms from mDSC showed a characteristic peak for all formulations with T_peak of around 45°C which suggested formation of a eutectic mixture. XRD data displayed that crystalline nature of ibuprofen was intact in the formulations. This work shows the effect of eutectic formation and micellar solubilization between ibuprofen and poloxamer at the given ratios on its solubility and dissolution rate enhancement.     

Highly pathogenic avian influenza H5N1 Clade 2.3.2.1c virus in migratory birds, 2014–2015

A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015. Based on the genetic and phylogenetic analyses, the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA, a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin. The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain (A/Alberta/01/2014). Further analysis showed that similar viruses have been circulating in wild birds in China, Russia, Dubai (Western Asia), Bulgaria and Romania (Europe), as well as domestic poultry in some regions of Africa. The affected areas include the Central Asian, East Asian-Australasian, West Asian-East African, and Black Sea/Mediterranean flyways. These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds, thus posing a serious threat to wild birds and potentially humans.

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