Representation of LGBTQIA in Bollywood Films

India produces more Hindi films than any other country. Film portrayals of society mirror that culture, which in turn shapes social attitudes. Hindi film, also referred to as Bollywood, exhibits strong societal roots. The Delhi High Court authorized homosexual behavior in the last ten years, but the Supreme Court later declared it to be unlawful. These modifications mirror modifications in social views. In this paper, we focus on how homosexuality is portrayed in Hindi films in relation to social attitudes about both male and female homosexuality. In India, cultural and social values and attitudes towards sexuality have historically been positive. However, during the 200 years of British colonial rule, these values and attitudes towards homosexuality and homosexual men and women became extremely negative and even punishable, in line with the prevalent Victorian views on sex and sexual activity. The literature has identified and documented several sexual descriptions and identities. In this essay, we discuss a tiny number of Hindi movies that deal with homosexuality. These representations have generally been unfavorable. We discuss the reasons why this would be the case as well as the effect that these portrayals might have on viewers

Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease

The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer's disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3 × Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3 × Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3 × Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3 × Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3 × Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3 × Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD

The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders. The actual cause and cascade of events in the progression of this pathology is not fully determined. AD is multifaceted in nature and is linked to different multiple mechanisms in the brain. This aspect is related to the lack of efficacious therapies that could slow down or hinder the disease onset/progression. The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway. Recently, the endocannabinoid system emerged as a novel potential therapeutic target to treat AD. In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD, although the mechanisms that are involved are not fully elucidated. This review provides an update of this area. In this review, we recapitulate the role of endocannabinoid signaling in AD and the probable mechanisms through which modulators of the endocannabinoid system provide their effects, thus highlighting how this target might provide more advantages over other therapeutic targets

Depressive-like behavior is paired to monoaminergic alteration in a murine model of Alzheimer's disease

Background: Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and have not yet been fully investigated in murine models. Methods: 18-month-old 3.Tg-AD Male mice and their wild-type Male littermates (non-Tg) were used. The open field test and the elevated plus maze test were used to evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail suspension test, and the sucrose preference test for antidepressant/depression-coping behaviors. Neurochemical study was conducted by microdialysis in freely-moving mice, analyzing the basal and K+-stimulated monoamine output in the frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which play a key role in the synthesis of monoamines. Results: Aged 3.Tg-AD mice exhibited a higher duration of immobility in the forced swim and tail suspension tests (predictors of depression-like behavior) which was not attenuated by a noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test, 3.Tg-AD mice showed a significantly lower sucrose preference compared to the non-Tg group, without any difference in total fluid intake. In contrast, the motor functions and anxiety-related emotional responses of 3.Tg-AD mice were normal, as detected by the open-field and elevated plus-maze tests. To strengthen these results, we then evaluated the monoaminergic neurotransmissions by in vivo microdialysis and immunohistochemistry. In particular, with the exception of the basal hippocampal dopamine levels, 3.Tg-AD mice exhibited a lower basal extracellular output of amines in the frontal cortex and ventral hippocampus and also a decreased extracellular response to K+ stimulation. Such alterations occur with obvious local amyloid-β and tau pathologies and without gross alterations in the expression of Tyrosin and Tryptophan hydroxylase. Conclusions: These results suggest that 3.Tg-AD mice exhibit changes in depression-related behavior involving aminergic neurotrasmitters and provide an animal model for investigating AD with depression

Depressive-like behavior is paired to monoaminergic alteration in a murine model of Alzheimer's disease

BACKGROUND: Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and have not yet been fully investigated in murine models. METHODS: 18-month-old 3×Tg-AD male mice and their wild-type male littermates (non-Tg) were used. The open field test and the elevated plus maze test were used to evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail suspension test, and the sucrose preference test for antidepressant/depression-coping behaviors. Neurochemical study was conducted by microdialysis in freely-moving mice, analyzing the basal and K(+)-stimulated monoamine output in the frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which play a key role in the synthesis of monoamines. RESULTS: Aged 3×Tg-AD mice exhibited a higher duration of immobility in the forced swim and tail suspension tests (predictors of depression-like behavior) which was not attenuated by a noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test, 3×Tg-AD mice showed a significantly lower sucrose preference compared to the non-Tg group, without any difference in total fluid intake. In contrast, the motor functions and anxiety-related emotional responses of 3×Tg-AD mice were normal, as detected by the open-field and elevated plus-maze tests. To strengthen these results, we then evaluated the monoaminergic neurotransmissions by in vivo microdialysis and immunohistochemistry. In particular, with the exception of the basal hippocampal dopamine levels, 3×Tg-AD mice exhibited a lower basal extracellular output of amines in the frontal cortex and ventral hippocampus and also a decreased extracellular response to K(+) stimulation. Such alterations occur with obvious local amyloid-β and tau pathologies and without gross alterations in the expression of Tyrosin and Tryptophan hydroxylase. CONCLUSIONS: These results suggest that 3×Tg-AD mice exhibit changes in depression-related behavior involving aminergic neurotrasmitters and provide an animal model for investigating AD with depression

Organogel: A Propitious Carman in Drug Delivery System

A gel is a semi-solid formulation having an external solvent phase that is either apolar (organogels) or polar (hydrogels) that is immobilized inside the voids contained in a three-dimensional networked structure. Organogels are bi-continuous systems composed of apolar solvents and gelators. When used at a concentration of around 15%, the gelators form self-assembled fibrous structures that become entangled with one another, resulting in the formation of a three-dimensional networked structure. The resulting three-dimensional networked structure blocks the flow of the external apolar phase. Sterol, sorbitan monostearate, lecithin, and cholesteryl anthraquinone derivatives are examples of gelators. The unique characteristics such as thermo-reversibility, viscoelasticity, and versatility impart a longer shelf-life, prolonged drug release, and patient compliance. These characteristics can easily be adjusted by simple formulation modifications, resulting in highly-structured architectures. Organogels are more likely to be used in various types of delivery systems because of their ability to entrap both hydrophilic and hydrophobic molecules inside their structure. Their combination with other materials allows for tailoring their potential as dosage forms. Organogels have potential applicability in numerous ways; hence this article discusses the various aspects of it

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 "mucoadhesive microspheres". [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) & 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 ''cytoadhesives". 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 'scenarios' 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 'First Generation'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

The endocannabinoid system in mental disorders: Evidence from human brain studies

Mental disorders have a high prevalence compared with many other health conditions and are the leading cause of disability worldwide. Several studies performed in the last years support the involvement of the endocannabinoid system in the etiopathogenesis of different mental disorders. The present review will summarize the latest information on the role of the endocannabinoid system in psychiatric disorders, specifically depression, anxiety, and schizophrenia. We will focus on the findings from human brain studies regarding alterations in endocannabinoid levels, cannabinoid receptors and endocannabinoid metabolizing enzymes in patients suffering mental disorders. Studies carried out in humans have consistently demonstrated that the endocannabinoid system is fundamental for emotional homeostasis and cognitive function. Thus, deregulation of the different elements that are part of the endocannabinoid system may contribute to the pathophysiology of several mental disorders. However, the results reported are controversial. In this sense, different alterations in gene and/or protein expression of CB1 receptors have been shown depending on the technical approach used or the brain region studied. Despite the current discrepancies regarding cannabinoid receptors changes in depression and schizophrenia, present findings point to the endocannabinoid system as a pivotal neuromodulatory pathway relevant in the pathophysiology of mental disorders.This study was supported by the Spanish Ministry of Economy and Competitiveness (SAF2015-67457-R, MINECO/FEDER), the Plan Estatal de I+D+i 2013-2016, the Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación, Spanish Ministry of Economy, FEDER (PI13/01529) and the Basque Government (IT616/13). I I-L is a recipient of a Predoctoral Fellowship from the Basque Government. E F-Z is a recipient of a Predoctoral Fellowship from the University of Cantabria. CM is a recipient of a Postdoctoral Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2016, ID 747487)