Impact of innate and adaptive immunity on rejection and tolerance

Until recently, research on transplantation rejection and tolerance has been directed toward deciphering the mechanisms of the adaptive immune system. However, the emergence that the innate immune system, the body's first-line defense against pathogens, has a strong influence on adaptive immunity has galvanized interest in elucidating the interplay between these two arms of the immune system. The discovery of Toll-like receptors and the characterization of the cellular mediators involved in innate immunity have provided growing evidence that innate immunity affects the adaptive immune response. Emerging evidence has also shown that early "danger signals"' associated with ischemia-reperfusion injury or brain death contribute to innate immune activation, promoting rejection, and inhibiting tolerance induction. In addition, nonspecific stimuli such as increased donor age or patient disease may also serve to exert a synergistic influence on innate immune activation. Ultimately, controlling the events in innate immune activation may help drive tolerance induction and reduce the rate of rejection.     

Stevioside protects against rhabdomyolysis‐induced acute kidney injury through PPAR‐γ agonism in rats

We explored the potential role of peroxisome proliferator activated receptor‐γ (PPAR‐γ) in stevioside‐mediated renoprotection using rhabdomyolysis‐induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol‐induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin–eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl‐2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR‐γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis‐induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside‐mediated renoprotection, which is suggestive of the involvement of PPAR‐γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis‐induced AKI, which may be attributed to modulation of PPAR‐γ expression.     

Protective effect on phenytoin-induced cognition deficit in pentylenetetrazol kindled mice: A repertoire of Glycyrrhiza glabra flavonoid antioxidants

Context: Glycyrrhiza glabra L. (Febaceae) has been widely used in traditional medicine and scientifically explored for its anticonvulsant and memory improving potential.

Objective: The objective of this study is to investigate the effect of flavonoid rich fraction of G. glabra root extract against phenytoin-induced cognition deficit in pentylenetetrazol (PTZ) kindled mice.

Materials and methods: The ethyl acetate fraction was initially screened in different in vitro free radical scavenging assays. For in vivo studies, the kindled mice in different groups were given 15?d post-treatment with phenytoin (25?mg/kg; p.o.) per se or in combination with varying doses of the fraction (5, 10, and 15?mg/kg; p.o.). Seizure severity score and cognitive functions were accessed using Racine's scale and passive shock avoidance paradigm, respectively on every 5th d after a PTZ challenge dose (35?mg/kg; i.p.). At the end of study, the animals were scarified for cerebral biochemistry.

Results: The fraction showed marked antioxidant activity indicated by low IC₅₀ values in DPPH (20.9?µg/mL), nitric oxide radical scavenging (195.2?µg/mL), and capacity of hydrogen peroxide scavenging (3.4?µg/mL) assays. Treatment with phenytoin per se and along with the flavonoid rich fraction showed significant reduction in seizure severity score as compared to vehicle control. The combined-treated groups also showed improved cognitive functions indicated by reduced number of mistakes and increased step-down latency in passive shock avoidance paradigm.

Conclusion: From the results, it can be concluded that the flavonoid rich fraction in combination with phenytoin reduces seizure severity and improve cognitive functions in PTZ-kindled mice.     

Association of heat shock proteins and neuronal membrane components with lipid rafts from the rat brain

Lipid rafts are specialized plasma membrane microdomains enriched in cholesterol and sphingolipids that serve as major assembly and sorting platforms for signal transduction complexes. Constitutively expressed heat shock proteins Hsp90, Hsc70, Hsp60, and Hsp40 and a range of neurotransmitter receptors are present in lipid rafts isolated from rat forebrain and cerebellum. Depletion of cholesterol dissociates these proteins from lipid rafts. After hyperthermic stress, flotillin-1, a lipid raft marker protein, does not show major change in levels. Stress-inducible Hsp70 is detected in lipid rafts at 1 hr posthyperthermia, with the peak levels attained at 24 hr, suggesting that Hsp70 may play roles in maintaining the stability of lipid raft-associated signal transduction complexes following neural stress.     

Anticonvulsant effect of Ficus religiosa: Role of serotonergic pathways

Ethnopharmacological relevance

Ficus religiosa (Moraceae) is reported to have numerous therapeutic utility in folk medicine. Among different biological activities on central nervous system, it has been reported to be used in ethnomedical treatment of epilepsy, which led us to further explore its anticonvulsant activity in various animal models of epilepsy.

Aim of the study

To investigate anticonvulsant activity of methanolic extract of figs of Ficus religiosa in animal models and to determine its possible anticonvulsant mechanism.

Materials and methods

Anticonvulsant activity of figs extract (25, 50 and 100 mg/kg, i.p.) was studied in seizures induced by maximum electroshock (MES), picrotoxin and pentylenetetrazol (PTZ). Cyproheptadine, a nonselective (5HT_1/2) serotonin antagonist (4 mg/kg, i.p.) was used to study the reversal of protective effect of extract in the above mentioned models. Acute toxicity, neurotoxicity and potentiation of pentobarbitone induced sleep by extract was also studied.

Results

Extract showed no toxicity, potentiated pentobarbitone induced sleep and inhibited seizures induced by MES and picrotoxin in a dose dependent manner. Anticonvulsant effect of extract was comparable to clinically used antiepileptic drugs (phenytoin and diazepam). However, PTZ induced seizures were not inhibited. Animals pretreated with cyproheptadine showed inhibition of the anticonvulsant effect of extract.

Conclusions

These findings suggested that the methanolic extract of figs of Ficus religiosa had anticonvulsant activity against MES and picrotoxin induced convulsions, with no neurotoxic effect, in a dose dependent manner. Inhibition of the anticonvulsant effect of extract by cyproheptadine substantiates the involvement of serotonergic pathways for the anticonvulsant activity of extract.     

Cardiovascular health among Asian Indians (CHAI): a community research project

The object of this research was to assess cardiovascular (CV) risks in Asian Indians in California. We conducted eight focus groups and a pilot survey using community-based participatory research (CBPR) methods. Focus groups were held in six communities. Surveys were conducted by telephone or in person in areas selected for high population densities of Asian Indians. We selected focus group subjects by snowball sampling (n = 57). We held six English and two Punjabi groups. We used a surname-based phone list from three area codes for telephone interviews (n = 254). We added 50 in-person interviews for comparison (total n = 304) and did 50 interviews in Punjabi. We held community meetings for dissemination. Focus groups discussed CV risks; themes developed aided survey development. In-person and telephone surveys were feasible. Telephone surveys were more gender-balanced and people more often answered alcohol, tobacco, and income questions. Self-reported prevalences for hypertension, hypercholesterolemia, and diabetes were 20.4, 35.3 and 10.6%, respectively. Only 11.9% of persons reported ever smoking cigarettes. It was concluded that CBPR methods were effective in this exploratory study assessing CV risks in Asian Indians. Hypertension, high cholesterol, and diabetes were more prevalent in participants than the population average; other risk factors were less common (tobacco).     

Post-Harvest Preservation of Whole Kinnow Fruit Using Betel Leaf Extract Coating

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The present study aimed at preserving Kinnow using betel leaf (Piper betle L.) extract. The purpose was to...