Rosuvastatin and retinoic acid may act as 'pleiotropic agents' against ß-adrenergic agonist-induced acute myocardial injury through modulation of multiple signalling pathways.

Cardiovascular disorders constitute the principal cause of deaths worldwide and will continue as the major disease-burden by the year 2060. A significant proportion of heart failures occur because of use and misuse of drugs and most of the investigational agents fail to achieve any clinical relevance. Here, we investigated rosuvastatin and retinoic acid for their "pharmacological pleiotropy" against high dose ß-adrenergic agonist (isoproterenol)-induced acute myocardial insult. Rats were pretreated with rosuvastatin and/or retinoic acid for seven days and the myocardial injury was induced by administering isoproterenol on the seventh and eighth day. After induction, rats were anaesthetized for electrocardiography, then sacrificed and different samples were collected/stored for various downstream assays. Myocardial injury with isoproterenol resulted in increased cardiac mass, decreased R-wave amplitude, increased QRS and QT durations; elevated levels of cardiac markers like cTnI, CK-MB, ALT and AST; increased lipid peroxidation, protein carbonylation and tissue nitric oxide levels; decreased endogenous antioxidants like SOD, CAT, GR, GST, GPx and total antioxidant activity; increased inflammatory markers like TNF-α and IL-6; decreased the mRNA expression of Nrf2 and Bcl-2; increased the mRNA expression of Bax, eNOS and iNOS genes. Pretreatment with rosuvastatin and/or retinoic acid mitigated many of the above biochemical and pathological alterations. Our results demonstrate that rosuvastatin and retinoic acid exert cardioprotective effects and may act as potential agents in the prevention of ß-adrenergic agonist-induced acute myocardial injury in rats. Cardioprotective potential of rosuvastatin and retinoic acid could be attributed to their influence on the redox pathways, immunomodulation, membrane stability, Nrf2 preservation, iNOS and Bax expression levels. Thus, they may act directly or indirectly at various steps, the breakpoints, in the pathophysiological cascade responsible for cardiac injury. Our study gives insights about the pharmacological pleiotropism of rosuvastatin and retinoic acid.

Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken.

Live intermediate plus infectious bursal disease virus (IBDV) vaccines (hot vaccines) are used for protection against the virulent IBDV strains in young chickens. We evaluated the potential of Toll-like receptor (TLR) agonists to alleviate hot vaccine-induced immunosuppression. The combination of Pam3CSK4 and poly I:C synergistically upregulated IFN-ß, IFN-γ, IL-12, IL-4, and IL-13 transcripts and cross-inhibited IL-1ß, IL-10, and iNOS transcripts in the chicken peripheral blood mononuclear cells (PBMCs) as analyzed by quantitative real-time PCR. Further, four-week old specific pathogen free White Leghorn chickens (n = 60) were randomly divided into six groups and either immunized with hot IBDV vaccine with or without Pam3CSK4 and/or poly I:C or not vaccinated to serve as controls. The results indicated that poly I:C alone and in combination with Pam3CSK4 alleviated vaccine-induced immunosuppression, as evidenced by greater weight gain, increased overall antibody responses to both sheep erythrocytes and live infectious bronchitis virus vaccine, upregulated IFN-γ transcripts and nitric oxide production by PBMCs (P < 0.05), and lower bursal lesion score in the experimental birds. In conclusion, poly I:C alone and its combination with Pam3CSK4 reduced the destruction of B cells as well as bursal damage with restoration of function of T cells and macrophages when used with a hot IBDV vaccine.

Lecithin-based deferoxamine nanoparticles accelerated cutaneous wound healing in diabetic rats.

Nanoparticles have higher frequency of being exposed to cells or tissue, and are thus more likely to gain access into cytoplasm or nuclei to modulate molecular events due to significantly larger surface area to volume ratio. As a result, they present amplified response or even different physiochemical and biomedical properties from bigger particles. Deferoxamine accelerates wound healing in diabetic rats by increased neovascularization, reduced inflammation and improved maturation of wound. We investigated the wound healing potential of deferoxamine-nanoparticles in diabetic rats. Lecithin based nanoparticles of deferoxamine were prepared and characterized. The diabetic rats were divided into five Groups, of which Group I was treated with pluronic-gel f-127 (25%), Group II with deferoxamine 0.1% and Group III, IV and V were treated with deferoxamine-nanoparticles incorporated in pluronic-gel f-127 25% at 0.03% (0.01% deferoxamine), 0.1% (0.03% deferoxamine) and 0.3% (0.1% deferoxamine) w/v respectively. The wound closure was significantly accelerated in group V as compared to control groups. HIF-1α, VEGF, SDF-1α, TGF-ß1, and IL-10 protein levels were significantly higher in group V. The collagen deposition and neovascularization was greater in deferoxamine-nanoparticle treated rats. In contrast, TNF-α level was lowest in group V. In summary, the deferoxamine-nanoparticle formulation we developed, when applied topically on diabetic wounds results in faster wound healing as compared to simple deferoxamine formulation. This formulation may prove to be an effective therapy for treatment of diabetic wounds.

Acute peripheral polyneuropathy with multiorgan failure: a diagnostic dilemma.

We describe the case of a young man who presented with abdominal pain, vomiting and acute symmetric peripheral polyneuropathy. He was noted to have high anion gap metabolic acidosis with high lactate levels and persistently high arterial and venous pO2 values. The cerebrospinal fluid was acellular with a high protein and the nerve conduction study was consistent with axonal sensorimotor neuropathy. His clinical condition deteriorated rapidly despite full supportive care and he subsequently died of multiorgan failure. An extensive workup for various infectious, autoimmune and other possible aetiologies was carried out to identify the underlying cause for his fulminant illness. All diagnostic workup was non-conclusive except for a significantly elevated serum aluminium level. We have discussed the possibility of aluminium phosphide poisoning in view of the clinical presentation.

Acute disseminated encephalomyelitis as the first presentation of CNS tuberculosis: report of a case with brief review.

Acute disseminated encephalomyelitis (ADEM) also known as post infectious encephalomyelitis is a demyelinating disease of the central nervous system (CNS) that typically presents as a monophasic disorder associated with multifocal neurological symptoms and disability. It may follow vaccination in children or infection. Viral infection like measles, rubella, influenza, Epstein bar, HIV, herpes, cytomegalusvirus (CMV) and West Nile virus have been implicated in the causation. Among bacteria, group A hemolytic streptococcus, mycoplasma pneumonia, Chlamydia, Rickettesia and leptospira have been shown to cause ADEM. There are few reports of ADEM due to tuberculosis (TB). We describe acute disseminated encephalomyelitis due to tuberculosis in a 35 year old female who initially started with neuropsychiatric manifestations and later developed florid neurological deficit and classical magnetic resonance imaging (MRI) lesions suggestive of the disease. The patient recovered completely after antitubercular therapy and is following our clinic for the last 12 months now.