Adenosine, a purine nucleoside has been described as a 'retaliatory metabolite' by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT) and Wolff Parkinson White (WPW) syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions.

Objective: To study the variation of disposition kinetic values of sparfloxacin in healthy, hepatopathic, and nephropathic chickens after a single intravenous administration. Materials and Methods: Hepatotoxicity was induced by the administration of paracetamol (500 mg / kg / day, p.o. for seven days) and nephrotoxicity by uranyl nitrate (2.0 mg / kg / day dissolved in distilled water, i.v. for four days) in chickens. Disposition kinetic studies of sparfloxacin were investigated in healthy as well as hepatopathic and nephropathic birds after a single intravenous administration at 40 mg / kg body weight. Results: Maximum plasma concentration detected at 0.16 hour was 31.25 ± 2.95, 61.95 ±1.85, and 99.86 ± 2.21 mg / ml in healthy, hepatopathic, and nephropathic group, respectively. The drug could not be detected in the plasma of healthy birds beyond 12-hour period, while the same was detectable for 72 hour in the plasma of hepatopathic and nephropathic birds. The concentration of sparfloxacin was significantly (P < 0.01) higher in all the samples of hepathopathic and nephropathic birds compared to healthy birds. All the kinetic values were increased (P < 0.01) in the hepatopathic and nephropathic birds, except Vd _area and Cl _B values in hepatopathic Birds; while β and Cl _B values nephropathic birds were decreased significantly than that of healthy birds. Conclusions: The dose of sparfloxacin may be reduced in hepatopathic as well as nephropathic birds.

Objectives: The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. Materials and Methods: The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. Results: The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 ± 1.0 µg/ml). Conclusions: The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents.

Objective: To evaluate the antioxidant status of chicken during cold stress and to investigate if there are any beneficial effects of Brahma Rasayana supplementation in cold stressed chicken. Materials and Methods: Activities of enzymatic and levels of non-enzymatic antioxidants in blood / serum and liver tissue were evaluated in chicken exposed to cold (4 ± 10C and relative humidity of 40 ± 5%, for six consecutive hours daily, for 5 or 10 days). The antioxidant properties of Brahma Rasayana (BR) supplementation (2 g/kg daily, orally) during cold stress was also studied. Results: There was a significant (P < 0.05) decrease in antioxidant enzyme in the blood, such as, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), and serum reduced glutathione (GSH) in cold stressed chicken. Serum and liver lipid peroxidation levels were significantly (P < 0.05) higher in cold stressed untreated chickens when compared to the treated and unstressed groups. There was also a significant (P < 0.05) increase in the antioxidant enzymes in the blood, such as, catalase (CAT) and SOD, in the liver CAT and SOD, and in GPX and GR in BR-treated cold stressed chicken, when compared to the untreated controls. Conclusions: Results of the present study conclude that in chicken, BR supplementation during cold stress brings about enhanced actions of the enzymatic and non-enzymatic antioxidants, which nullify the undesired side effects of free radicals generated during cold stress.

Objective: The aim of this study was to investigate anti-inflammatory and hepatoprotective activities of Plantago major L. (PM). Materials and Methods: Anti-inflammatory activity: Control and reference groups were administered isotonic saline solution (ISS) and indomethacin, respectively. Plantago major groups were injected PM in doses of 5 mg/kg (PM-I), 10 mg/kg (PM-II), 20 mg/kg (PM-III) and 25 mg/kg (PM-IV). Before and three hours after the injections, the volume of right hind-paw of rats was measured using a plethysmometer. Hepatoprotective Activity: The hepatotoxicity was induced by carbon tetrachloride (CCl4) administration. Control, CCl4 and reference groups received isotonic saline solution, CCl4 and silibinin, respectively. Plantago major groups received CCl4 (0.8 ml/kg) and PM in doses of 10, 20 and 25 mg/kg, respectively for seven days. Blood samples and liver were collected on the 8th day after the animals were killed. Results: Plantago major had an anti-inflammatory effect matching to that of control group at doses of 20 and 25 mg/kg. It was found that reduction in the inflammation was 90.01% with indomethacin, 3.10% with PM-I, 41.56% with PM-II, 45.87% with PM-III and 49.76% with PM-IV. Median effective dose (ED50) value of PM was found to be 7.507 mg/kg. Plantago major (25 mg/kg) significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels when compared to the CCl4 group. The histopathological findings showed a significant difference between the PM (25 mg/kg) and CCl4 groups. Conclusion: The results showed that PM had a considerable anti-inflammatory and hepatoprotective activities.

Objective: To evaluate the antihyperglycemic activity of atorvastatin and hydroxychloroquine combination in alloxan-induced diabetic rats. Materials and Methods: Alloxan induced diabetic Wistar male rats were randomized into six groups of 6 rats each. (Normal rats, diabetic control, atorvastatin (ATV), hydroxychloroquine (HCQ), ATV 5 mg /kg + HCQ 100 mg/kg, and ATV 10 mg/kg + HCQ 200 mg/kg). The rats were treated for 9 days and blood samples were collected at baseline and end of therapy. These samples were analyzed for plasma glucose by autoanalyzer. Changes in body weight, water, food intakes and total protein content were also recorded. Results: Atorvastatin and hydroxychloroquine alone and in combination reported significant fall in blood glucose level from baseline. Fall in glucose level was significantly more in high dose combination of atorvastatin and hydroxychloroquine (ATV: 10 mg/kg + HCQ: 200 mg/kg) as compared to other study treatment groups (ATV: 17% Vs HCQ: 7% Vs ATV 5mg/kg + HCQ 100mg /kg: 14% Vs ATV 10mg/kg + HCQ 200mg /kg: 21%; p<0.01). ATV and HCQ individually and in combination also improved the body weight loss. The weight gain was significantly more in combination treated rats as compared to positive control group and greater than those who received atorvastatin and hydroxychloroquine alone. Rats treated with the combination also reported significant decrease in food intake and significant increase in total protein. Conclusion: Increased hypoglycemic effect in combination may be due to potentiation or synergism between HCQ and ATV. Further studies are required to demonstrate clinically significant antidiabetic effect.

Objectives: Screening of the medicinal plants and determination of minimum inhibitory concentration (MIC) against Vibrio cholerae and Vibrio parahaemolyticus. Materials and Methods: A simple in vitro screening assay was employed for the standard strain of Vibrio cholerae, 12 isolates of Vibrio cholerae non-O1, and Vibrio parahaemolyticus. Aqueous and organic solvent extracts of different parts of the plants were investigated by using the disk diffusion method. Extracts from 16 medicinal plants were selected on account of the reported traditional uses for the treatment of cholera and gastrointestinal diseases, and they were assayed for vibriocidal activities. Results: The different extracts differed significantly in their vibriocidal properties with respect to different solvents. The MIC values of the plant extracts against test bacteria were found to be in the range of 2.5-20 mg/ml. Conclusions: The results indicated that Lawsonia inermis, Saraca indica, Syzygium cumini, Terminalia belerica, Allium sativum, and Datura stramonium served as broad-spectrum vibriocidal agents.

Objective: To investigate the effect of Ocimum sanctum, ascorbic acid, and verapamil on macrophage function and oxidative stress in experimental animals exposed to cocaine. Materials and Methods: Mice were used in this study and were divided randomly into different groups of six animals each. They were either treated with intraperitoneal injection of saline or cocaine hydrochloride or an oral feeding of oil of Ocimum sanctum, ascorbic acid or verapamil, or both (ascorbic acid and verapamil), and were evaluated for a respiratory burst of macrophages, superoxide and nitric oxide (NO) production, estimation of TNF-a in the serum and supernatant of cultured macrophages, estimation of lipid peroxidation (malondialdehyde- MDA) in the serum, and superoxide dismutase activity in the erythrocytes. Results: Unstimulated respiratory burst as well as superoxide production was enhanced on treatment with cocaine and all the three drugs were found to attenuate this enhancement. The bactericidal capacity of macrophages decreased significantly on chronic cocaine exposure, as it was associated with decreased respiratory burst and superoxide production. There was a significant decrease in NO production by macrophages on chronic cocaine exposure and all the test drugs were found to restore nitrite formation to a normal level. There was an increase in the malonylodialdehyde (MDA) level and decrease in the superoxide dismutase level on chronic cocaine exposure, and all the three drugs effectively decreased the MDA level and increased superoxide dismutase level. There was an increase in serum TNF-α on chronic cocaine exposure, which was decreased significantly by ascorbic acid and verapamil. Conclusion: O. sanctum, ascorbic acid, and verapamil were equally effective in improving the macrophage function and reducing oxidative stress. These findings suggested that O. sanctum, ascorbic acid, and verapamil attenuated acute and chronic cocaine-mediated effects.

Objective: To study the mechanism involved in hydrogen peroxide (H ₂ O ₂ ) or tert-butyl hydroperoxide (t-BHP)-induced potentiation of the Ang II-mediated contraction of isolated rat thoracic aorta. Materials and Methods: Thoracic aorta was isolated from the Sprauge dawley rats (300-320 gm), cut spirally and response to Ang II (5 ´ 10 ^-8 M) was taken in the absence and presence of H ₂ O ₂ (10 ^-6 M) and t-BHP (10 ^-5 M). To explore the probable mechanism of H ₂ O ₂ and t-BHP-induced potentiation of Ang II-mediated contractile response, different blockers such as losartan (AT ₁ receptor blocker; 1 µM), catalase (H ₂ O ₂ scavenger; 500 U/ml), lercanidipine (L-type calcium channel blocker; 1 µM), geinistein (tyrosine kinase inhibitor; 100 µM), and indomethacin (cyclo-oxygenase inhibitor; 10 µM) were used. Results: In spiral preparation of rat thoracic aorta, H ₂ O ₂ (10 ^-6 M) and t-BHP (10 ^-5 M) did not produce the contraction as such. However, when they are added simultaneously with Ang II (5 ´ 10 ^-8 M), they potentiated the contractile response of the Ang II. Catalase (500 U/ml) partially antagonized the Ang-II-induced contraction, as well as antagonized the potentiation induced by H ₂ O ₂ . Losartan (1 µM) and lercanidipine (1 µM) antagonized the Ang II-induced contractile response without affecting H ₂ O ₂ (10 ^-6 M)-mediated potentiation. Geinistein (100 µM) antagonized H ₂ O ₂ (10 ^-6 M)-mediated potentiation, but it slightly decreased the Ang II response. Losartan (1 µM) and lercanidipine (1 µM) and Geinistein (100 µM) antagonized the Ang II-induced contractile response but not t-BHP-mediated potentiation. Indomethacin antagonized t-BHP-mediated potentiation without affecting much of Ang II response. Conclusion: From the above-mentioned results, we can reasonably conclude that H ₂ O ₂ and t-BHP potentiated the contraction induced by the Ang II. H ₂ O ₂ -induced potentiation of Ang II response may be mediated through tyrosine kinase activation and t-BHP through the activation of cyclo-oxygenase enzyme.

Objectives: In the present study, central effects of physostigmine and atropine have investigated in the formalin-induced pain in rats. Materials and Methods: In conscious rats implanted with an intracerebroventricular (i.c.v.) cannula, the effects of i.c.v. injection of physostigmine and atropine were investigated on the formalin test in the rat. Formalin test was induced by subcutaneous (s.c.) injection of formalin (50 µl, 1%) in ventral surface of left hind paw, and durations of licking and biting of the injected paw were measured in 5-min blocks for 1 h. Results: Formalin produced a biphasic response (first phase: 0-5 and second phase: 15-40 min) in durations of licking and biting of the injected paw. Physostigmine at doses of 2.5, 5 and 10 ug significantly (P < 0.05) attenuated both first and second phases of pain response. Atropine (5 and 10 ug), used alone, produced no significant effect on pain, but pretreatment with atropine (10 ug) significantly (P < 0.05) blocked antinociception induced by physostigmine (5 ug). Conclusion: These results indicate that i.c.v. physostigmine can affect both neurogenic and inflammatory phases of formalin-induced pain through a mechanism in which the muscarinic cholinergic receptors are involved.

Sildenafil is used in infants and children mainly for the treatment of pulmonary hypertension associated with congenital heart disease. Some side-effects of sildenafil are similar to the symptoms and signs of congestive heart failure in children. We present a case of a two-month-old infant with supracardiac total anomalous venous connection and pulmonary hypertension, who presented with severe sweating and tachycardia after institution of sildenafil therapy. He improved dramatically on discontinuation of the drug.