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Influenza (flu) is caused by a highly contagious virus that is spread by coughs and sneezes. Flu symptoms include high fever, chills and sweating, sore throat, weakness, headache, muscle and joint pains, and cough. Older people and those with an underlying medical condition are more likely to develop serious complications, including secondary bacterial pneumonia, primary influenza pneumonia, and inflammation of the brain or heart. There are three types of flu virus: A, B, and C. The flu virus has a unique ability to change its surface structure. This allows it to escape recognition by the body’s immune system and cause widespread illness (epidemics and pandemics). Most cases of influenza occur within a 6- to 8-week period during winter and spring. Epidemics occur when there are minor changes in the nature of the virus so that more people within a community are susceptible. Influenza A is more likely to cause epidemics. Pandemics (worldwide epidemics) occur when there are major changes in the virus so that the disease affects a large proportion of people in a geographic region or on more than one continent. The findings presented in this article have many important implications for understanding the influenza A (H1N1) viral pathogenesis, prevention, and treatment. Direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by virus infection. Nitric oxide and oxygen free radicals such as superoxide anion (O 2 –· ) are generated markedly in influenza A (including H1N1) virus-infected host boosts, and these molecular species are identified as the potent pathogenic agents. The mutual interaction of nitric oxide (NO) with O 2 –· resulting in the formation of peroxynitrite is operative in the pathogenic mechanism of influenza virus pneumonia. Influenza virus infection involves pathological events in which oxygen free radicals play an important role in the pathogenesis. The toxicity and reactivity of oxygen radicals generated in excessive amounts mediate the overreaction of the host’s immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold. With 30,000 deaths and 200,000 hospitalizations from the seasonal flu, those numbers are certainly higher than what we have seen of the swine flu. Protecting yourself from both viruses is very important. Kristi Yamaguchi

Background: Changes in leukocyte-endothelial and microvascular perfusion are hallmark events in inflammation. Thus, protection of the intestinal microcirculation represents a pivotal therapeutic target in systemic inflammation and sepsis. The endocannabinoid system (ECS) modulates a number of critical homeostatic functions and has been associated with anti-inflammatory responses. Our study aimed to examine intestinal leukocyte adhesion and capillary perfusion following selective inhibition of the endocannabinoid degradation enzyme, fatty acid amide hydrolase (FAAH), in experimental sepsis (endotoxemia). Methods: Five groups of rats were used: controls, endotoxemia [lipopolysaccharide (LPS)], FAAH inhibitor URB597 (0.3 mg/kg)+LPS, URB597 (0.6 mg/kg)+LPS, and URB597 (0.6 mg/kg)+cannabinoid 2 receptor (CB 2 R) antagonist (AM630)+LPS. After 2 h, intravital microscopy was performed to quantify intestinal leukocyte recruitment and functional capillary density (FCD), as well as macrohemodynamic monitoring and histological examinations. Results: LPS induced a significant increase in leukocyte adhesion in collecting and postcapillary submucosal venules and a decrease in intestinal FCD. URB597 pretreatment prevented the LPS-induced increase in leukocyte adhesion in intestinal venules and a decrease in intestinal FCD. The administration of the CB 2 R inhibitor, AM630, with URB597 reversed the protective effects of URB597 on the LPS-induced increase in leukocyte adhesion in intestinal venules, but not URB597’s effect on the intestinal FCD. Conclusions: FAAH inhibition prevents the LPS-induced increase in leukocyte adhesion and improves the capillary perfusion of the gut. This might be mediated in part by CB 2 R activation. Our study encourages further investigation into the therapeutic potential of drugs targeting the ECS in sepsis.

Background: The use of medicinal plants has turned out to be an alternative method for the treatment of diseases, such as diabetes mellitus. The recommendation of the World Health Organization Committee on Diabetes encouraging research on hypoglycemic agents of plant origin used in traditional medicine has greatly motivated research in this area. The hypoglycemic activity of Ipomoea digitata tuber extract was investigated in streptozotocin-induced diabetic rats. Methods: An oral administration of the hydroalcoholic extract of I. digitata tuber (100 and 200 mg/kg) and glibenclamide was given for 28 days. Blood glucose levels were measured at 0, 2, 4, 6, and 24 h in the acute study and at 0, 7, 14, 21, and 28 days in the chronic study. The weight of rats was recorded before and after the study period of 28 days. Results: In the acute study, both doses of the extract showed a significant reduction in the blood glucose level compared with the control but less significant than glibenclamide. In the chronic study, all treatments showed a significant blood glucose reduction in diabetic rats. The extract and glibenclamide not only prevented a further body weight loss but also maintained the body weight during the study period. Conclusions: The result of the study concluded that I. digitata exhibits a considerable hypoglycemic activity, which could be due to the presence of flavonoids and β-sitosterol as active principles, although the mechanism of action remains to be determined. Thus, the plant can be the key contributor in the treatment of diabetes as an alternative medicine.

Background: This study investigates the protective role of polyphenolic-rich extract from Sorghum bicolor against diethylnitrosamine (DEN)-induced redox imbalance in rat microsomes. Methods: Reactive oxygen species (ROS) scavenging potentials of the polyphenolic extract from S. bicolor (0.2–1.0 mg/mL) was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide ion, hydrogen peroxide, hydroxyl radical, and ferric ion reducing system. The detoxification of ROS was evaluated in DEN-induced redox imbalance in rat microsomes. Results: Sorghum bicolor polyphenolic extract at 1.0 mg/mL scavenged the DPPH, superoxide ion, hydrogen peroxide, and hydroxyl radical at 75%, 76%, 79%, and 81%, respectively; it also reduced ferric ion significantly. The polyphenolic extract significantly (p<0.05) attenuated DEN-mediated decrease in the activities of ROS detoxifying enzymes (superoxide dismutase, catalase, glutathione peroxidase and reductase, and glucose-6-phosphate dehydrogenase). The concentrations of malondialdehyde, conjugated dienes, lipid hydroperoxide, protein carbonyl, and percentage DNA fragmentation in DEN-treated microsomes were significantly reduced by the polyphenolic extract. Conclusions: The results of the present study indicated that S. bicolor polyphenolic extract possessed in vitro antioxidant activity and protected microsomes from DEN-mediated oxidative stress by scavenging free radicals and ROS scavenger and inducer of ROS detoxifying enzymes.

Background: The present study aimed to determine the effect of Trichopus zeylanicus leaf extract (TZ Et) on mercuric chloride (HgCl 2 )-induced liver toxicity in rats. Methods: Wistar albino male rats were divided into four groups. Group I was administered physiological saline as a vehicle control. Group II was administered HgCl 2 (0.4 mg/kg body weight/day) intraperitoneally for 20 days. Groups III and IV were administered TZ Et orally (100 mg/kg body weight/day) for 20 days with or without intraperitoneal administration of HgCl 2 . Serum hepatic marker enzymes, enzymic and non-enzymic antioxidants, liver functional markers, lipid peroxidation, and liver histology were evaluated. Results: The toxic effect of HgCl 2 was indicated by the significantly (p<0.05) increased serum marker enzymes, liver functional markers, and lipid peroxidation. The activities of enzymic and non-enzymic antioxidants were significantly (p<0.05) decreased. TZ Et significantly (p<0.05) prevented these pathological alterations as observed by histology. Conclusions: The present study concludes that TZ Et has the ability to alleviate the hepatotoxic effects caused by HgCl 2 in rats.

Background: The present study aimed to evaluate the antihyperlipidemic effect of ferulic acid (FA) on carbon tetrachloride (CCl 4 )-treated rats. Methods: Female albino rats of the Wistar strain were used in the present study. The rats were divided into four groups: groups 1 and 4 received physiological saline (3 mL/kg body weight/week) by subcutaneous injection, whereas groups 2 and 3 received a subcutaneous injection of CCl 4 (3 mL/kg body weight/week) for a total period of 12 weeks. In addition, groups 3 and 4 were administered FA (20 mL/kg body weight) every day for the last 90 days. Results : The results showed significantly (p≤0.05) elevated levels of cholesterol, triglycerides (TG), and free fatty acids (FFA) in the liver and kidney of CCl 4 -treated rats as compared with those of the controls. In addition, the levels of cholesterol, FFA, phospholipids (PL), and TG were elevated significantly in the circulation. Administration of FA effectively reduced these levels of lipids in the plasma, liver, and kidney of CCl 4 -treated rats. The PL level was significantly decreased in the liver and kidney of CCl 4 -treated rats and was positively modulated by FA treatment. Our histopathological observations were also in correlation with the biochemical parameters. Conclusions: From the results obtained, we could conclude that FA effectively protects the system against hyperlipidemia and may be an effective therapeutic agent for the treatment of this disorder.

Background: Glucocorticoids (GCs) exert a wide range of anti-inflammatory, immunosuppressive, and antineoplastic activities. The aim of our investigation was to elucidate the effect of dexamethasone, a synthetic GC, on polyamine metabolism in the rat thymus. Methods: Male albino Wistar rats, weighing 180–230 g, were divided into two groups: control and experimental. The experimental group received dexamethasone intraperitoneally for 3 days, in a daily dose of 4 mg/animal. The last dose of the hormone was applied on the 3rd day, 1 h before killing. The control group received 0.9% NaCl instead of the hormone. The animals were killed by decapitation. The thymus was removed quickly and rinsed with ice-cold saline. Polyamines were extracted using butanol. The amount of polyamines was investigated by electrophoresis. For the estimation of polyamine oxidase (PAO) activity, 10% water homogenate was prepared. Results: Our results suggested that dexamethasone supplementation of experimental animals for 3 days significantly decreased the spermine (Sp) and spermidine (Spd) levels in rat thymus tissue (Sp Control, 362.56±25.33 nmol/g wet weight; Sp Exp. Group, 313.01±21.16 nmol/g wet weight; Spd Control, 673.81±30.95 nmol/g wet weight; Spd Exp. Group, 410.21±17.26 nmol/g wet weight). PAO activity significantly decreased under hormone influence in comparison with the control group (PAO Control, 0.449±0.121 U/mg prot.; PAO Exp. Group, 0.312±0.096 U/mg prot.). Conclusions: The decrease in polyamine amounts in the rat thymus is not due to the change in PAO activity.

Background: Altered regulation of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) is present in liver cirrhosis. Several experimental studies have shown that selective modulation of NO metabolism in the liver reduces intrahepatic resistance and portal pressure in cirrhosis. This preliminary study investigated whether selective inhibition of phosphodiesterase-5 (PDE-5), which prevents the conversion of cGMP to 5′-GMP, as well as non-selective inhibition of PDE isozymes could ameliorate hepatic toxicity induced by paracetamol (PCM). Methods: PCM (250 mg/kg, i.p.) was administered to induce hepatotoxicity. Control rats received physiological saline (10 mL/kg, p.o.), while sildenafil (a selective PDE-5 inhibitor) and aminophylline (a non-selective PDE inhibitor) were administered separately at 10 mg/kg p.o. to PCM-treated rats. Results: PCM hepatotoxicity, characterized by elevation of aspartate and alanine aminotransferases, hepatic degeneration, and centrilobular necrosis, was attenuated by both PDE inhibitors. Sildenafil and aminophylline significantly (p<0.05) reduced plasma aspartate aminotransferase activity by 49.6% and 39.8%, respectively, with moderate increase in alanine aminotransferase activity by 26.1% and 20.4%, respectively, in PCM-treated rats. Decreases in total protein and albumin induced by PCM were significantly (p<0.05) prevented by 30.0% and 22.2%, respectively, following sildenafil administration, while aminophylline decreased these proteins by 14.0% and 25.9%, respectively. Sildenafil and aminophylline significantly (p<0.05) reduced lipid peroxidation by 30.7% and 19.7%, respectively, while moderately increasing glutathione (GSH) in the PCM-treated rats. Both drugs did not significantly alter the total cholesterol and triglyceride levels. Conclusions: These preliminary data suggest that pharmacological inhibition of PDE isozymes may be a useful strategy in protecting against PCM hepatic toxicity.

Background: Nerve growth factor (NGF) is a neurotrophin that supports the survival and differentiation of sympathetic neurons, and its increased expression after myocardial infarct was correlated with cardiac sympathetic hyperinnervation and arrhythmias. However, it is unclear whether NGF protects the heart during infarct. In this study, we sought to address this issue in rat heart exposed to ischemia/reperfusion injury (IRI). Methods: NGF was administered intravenously (IV), 15 min before ischemia, at different concentrations in the absence or presence of inhibitors of phosphatidylinositol-3 kinase (PI 3 K) or nitric oxide synthase (NOS) in different groups of rats (n=6) with left coronary occlusion for 30 min followed by 120-min reperfusion. The area at risk and infarct to risk ratios were determined from sections stained with 1% 2,3,5-triphenylterazolium chloride. Results: NGF treatment at doses of 0.015–15 μg/kg, with an optimal dose of 0.15 μg/kg given IV before ischemia, reduced the infarct size from about 60% at the area of risk to about 25%, indicating cardioprotection by about 60%. The infarct-sparing effects of NGF were partially abolished by the inhibition of PI 3 K and NOS using wortmannin and N (G)-monomethyl-l-arginine, respectively. Conclusions: We have demonstrated for the first time that NGF attenuates myocardial infarct damage in an in vivo rat model of myocardial regional IRI. This cardioprotective effect is proposed to be related to the activities of PI 3 K and NOS. This suggests that NGF has a potential therapeutic role in the treatment of IRI.