A SYNERGISTIC DECLINE IN HUMORAL AND CELLULAR IMMUNITY OF DIABETIC MICE ON EXPOSURE TO POLLUTED AIR

Abstract: It is clinically known that diabetic patients are more prone to infectious diseases, due to low immune status. Since, some of the common air pollutants are reported to suppress immune system, how exposure to artificially polluted air influences the immune responses in experimental diabetic mice was studied. A diabetic state was induced by alloxan and mice were exposed to artificially polluted air for 30 days. During the period of exposure, the humoral (antibody titer) and cellular (foot and swelling) immune responses to antigenic challenges with sheep RBC were investigated. The exposure to polluted air produced a significant decline in the immune responses in non-diabetic mice whereas a synergistic decline was observed in diabetic group. Since, daily oral treatment with vitamin E 050mg/kg) significantly prevented the pollution induced immunosuppression, the involveme:1t of free radicals is suggested

Research Paper - Pyrogallol: A novel tool for screening immunomodulators

OBJECTIVE:To induce immunosuppression in rats by pyrogallol and to develop a novel model to screen the immunomodulatory activity of a known agent. MATERIAL AND METHODS: In order to induce immunosuppression, pyrogallol was daily administered to rats for 7 days in different doses (10, 25, 50 and 100 mg/kg, i.p.). On Day 7 and 13, the rats were sensitized with sheep red blood cells (SRBC) to assess the humoral immune response. On Day 20, SRBC were injected in the subplantar region of the hind paw, and an increase in the paw volume was recorded on Day 22 to assess the cell-mediated immune responses. The phagocytosis in the peritoneal macrophages was assessed on the last day. The parameters of oxidative stress such as lipid peroxidation (LPO), reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities were assessed on the last day. In another set of experiment, the immunomodulatory activity of Rubia cordifolia (RC) (50, 100, and 200 mg/kg, p.o., daily from Day 1 to Day 22) was screened in rats in whom immunosuppression was induced by a minimum effective dose of pyrogallol (50 mg/kg). RESULTS: The dose of 25 mg/kg of pyrogallol suppressed only the humoral immunity (P<0.05), while 50 and 100 mg/kg dose significantly (P<0.01) impaired all the parameters i.e. humoral immunity, cell-mediated immunity and phagocytosis (P<0.01). It also caused a dose-dependent increase in the LPO levels, depletion of GSH, and decrease in activities of SOD and CAT. The treatment with the alcoholic extract of Rubia cordifolia significantly prevented the influence of the minimum effective dose of pyrogallol (50 mg/kg) on all immunological parameters and concurrently prevented the changes in the marker parameters of oxidative stress. The dose of 100 mg/kg was found to be optimum for this purpose. CONCLUSION: Fifty mg/kg (i.p., daily for 7 days) appears to be the minimum dose of pyrogallol, which can induce significant immunosuppression in rats. The correlation analysis indicated that pyrogallol-induced immunosuppression is related to oxidative stress. In addition, it was found that the immunomodulatory activity of a known agent could be successfully screened by this method. Thus, pyrogallol can be used as an experimental tool to induce immunosuppression while screening the immunomodulatory activity of any agent

Development and evaluation of a hot-melt coating technique for enteric coating

Conventional enteric coating requires the use of organic based polymers which are equally hazardous to the environment and operating personnel. Hot-melt coating avoids the use of solvents and is a safer and time-saving process. The present study was designed to assess the efficacy of hot-melt coating (HMC) as an enteric coating technique. Pellets prepared by extrusion spheronization were selected as the core formulation for a model of the gastric irritant drug diclofenac sodium (DFS) because of their innate advantages over single-unit formulations. Stearic acid (SA) and palmitic acid (PA) were evaluated as enteric hot-melt coating materials. HMC was carried out in a specially modified coating pan by applying SA and PA in molten state onto preheated pellets to achieve a coating level of 5-15 %w/w. Hot-melt coated pellets were evaluated for disintegration pH and in vitro dissolution in the pH range 1.2 to 6.8, along with basic micromeritics. SEM of coated pellets showed a uniform and smooth coating. These results indicated that HMC of both SA and PA exhibited very good enteric coating ability. The coated pellets showed negligible drug release in acidic pH. As the pellets were subsequently transferred to a higher pH level, a gradual increase in release of the drug from the pellets was observed with increasing pH of the dissolution media. The release was dependent upon coating extent, providing sustained enteric release as opposed to abrupt release with mixed release kinetics.<br>O revestimento entérico convencional requer o uso de polímeros orgânicos os quais são igualmente danosos ao meio ambiente e ao pessoal que o executa. O revestimento por fusão a quente evita o uso de solventes e é processo mais seguro e que consome menos tempo. O presente estudo foi planejado para avaliar a eficácia do revestimento por fusão a quente (RFQ) como técnica de revestimento entérico. Os péletes preparados por esferonização por extrusão foram selecionados como formulação central para modelo de fármaco irritante gástrico, o diclofenaco sódico (DFS) em razão das vantagens inerentes sobre as formulações de única dose. O ácido esteárico (AE) e o ácido palmítico (AP) foram avaliados como materiais para o revestimento de fusão a quente. O RFQ foi realizado em recipiente especialmente modificado, aplicando AS e PA no estado fundido em péletes pré-aquecidos para atingir nível de revestimento de 5 a 15% p/P. Os péletes revestidos por fusão a quente for avaliados quanto ao pH de desintegração e à dissolução in vitro na faixa de pH de 1,2 a 6,8, juntamente com base micromerítica. O SEM dos péletes revestido mostrou revestimento uniforme e plano. Esses resultados indicaram que o RFQ tanto do AE quanto do AP apresentou capacidade de revestimento muito boa. Os péletes revestidos mostraram pouca liberação do fármaco em pH baixo. Como os péletes foram, subsequentemente, transferidos para pH mais altos, observou-se aumento gradual na liberação do fármaco dos péletes com o aumento do pH do meio de dissolução. A liberação foi dependente da extensão do revestimento, sendo a liberação entérica controlada, contrariamente à liberação abrupta com cinéticas mistas

Imunomodulatorni učinak antiestrogenih lijekova

There are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulatorsby alteringthe function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.Postoje značajni eksperimentalni, epidemiološki i klinički dokazi da na patologiju karcinoma dojke utječu endogeni hormoni. Zbog toga je snižavanje razine hormona najvažniji način terapije ove bolesti. Već više od tri dekade koristi se tamoksifen, kompetitivni parcijalni agonist-inhibitor receptora za estrogene. U suvremenoj terapiji koriste se još raloksifen, različiti inhibitori aromataze (posebno treća generacija inhibitora) i agonisti hormona za oslobađanje luteinizirajućeg hormona. U posljednje vrijeme sve više činjenica ukazuje na to da ti lijekovi imaju i imunomodulatorni učinak, tj. utječu na funkciju leukocita i oslobađanje različitih citokina. Štoviše, postoje dokazi da antiestrogeni lijekovi imaju povoljni učinak na neke autoimune bolesti. Međutim, njihov imunofarmakološki učinak nije do kraja objašnjen. Samo potpuno razumijevanje patofizioloških procesa može uroditi učinkovitom strategijom za prevenciju i terapiju te smanjenje mortaliteta od karcinoma dojke

Altered serotonergic function may partially account for behavioral endophenotypes in steroid sulfatase-deficient mice

The X-linked gene STS encodes the steroid hormone-modulating enzyme steroid sulfatase. Loss-of-function of STS, and variation within the gene, have been associated with vulnerability to developing attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition characterized by inattention, severe impulsivity, hyperactivity, and motivational deficits. ADHD is commonly comorbid with a variety of disorders, including obsessive–compulsive disorder. The neurobiological role of steroid sulfatase, and therefore its potential role in ADHD and associated comorbidities, is currently poorly understood. The 39,XY*O mouse, which lacks the Sts gene, exhibits several behavioral abnormalities relevant to ADHD including inattention and hyperactivity. Here, we show that, unexpectedly, 39,XY*O mice achieve higher ratios than wild-type mice on a progressive ratio (PR) task thought to index motivation, but that there is no difference between the two groups on a behavioral task thought to index compulsivity (marble burying). High performance liquid chromatography analysis of monoamine levels in wild type and 39,XY*O brain tissue regions (the frontal cortex, striatum, thalamus, hippocampus, and cerebellum) revealed significantly higher levels of 5-hydroxytryptamine (5-HT) in the striatum and hippocampus of 39,XY*O mice. Significant correlations between hippocampal 5-HT levels and PR performance, and between striatal 5-HT levels and locomotor activity strongly implicate regionally-specific perturbations of the 5-HT system as a neurobiological candidate for behavioral differences between 40,XY and 39,XY*O mice. These data suggest that inactivating mutations and functional variants within STS might exert their influence on ADHD vulnerability, and disorder endophenotypes through modulation of the serotonergic system