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  1. Atif Abbas S, Sharma JN, Pauzi A, Yusof M
    Gen. Pharmacol., 1999 Sep;33(3):243-7.
    PMID: 10480657
    The present study was conducted to examine the effect of bradykinin and bradykinin 2 receptor antagonist on survival time in rats with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure responses in the presence and absence of bradykinin and its antagonist. Bradykinin treatment (4 microg and 8 microg/kg IV) significantly (p < 0.05) increased the survival time of rats compared with saline-treated rats with coronary artery ligation for 15 min and continuously. The heart rate and blood pressure responses were significantly (p < 0.001) altered in the presence of coronary artery ligation. Bradykinin antagonist treatment (4 microg/kg IV) abolished the effect of bradykinin and thus reduced the survival time of rats with coronary artery ligation. The mean value of survival time between saline-treated and bradykinin antagonist- plus bradykinin-treated rats did not differ significantly (p > 0.05).
  2. Fredalina BD, Ridzwan BH, Abidin AA, Kaswandi MA, Zaiton H, Zali I, et al.
    Gen. Pharmacol., 1999 Oct;33(4):337-40.
    PMID: 10523072
    Fatty acid profile from crude extracts of local sea cucumber Stichopus chloronotus was determined using gas chromatography (GC) technique. The extracts were prepared separately in methanol, ethanol, phosphate buffer saline (PBS), and distilled water as part of our study to look at the affinity of these solvents in extracting the lipid from sea cucumber. The PBS and distilled water extractions indicate water-soluble components, while the organic fractions are extracted in methanol and ethanol as organic solvents. Furthermore, water extraction is the conventional method practiced in Malaysia. In our analysis the C14:0 (myristic), C16:0 (palmitic), C18:0 (stearic), C18:2 (linoleic), C20:0 (arachidic), and C20:5 (eicosapentaenoic, EPA) were significantly different (p < 0.01) in the four solvent extractions. However, the PBS extraction contained a much higher percentage of EPA (25.69%) compared to 18.89% in ethanol, 7.84% in distilled water, and only 5.83% in methanol, and variances were significantly different (p < 0.01 ). On the other hand, C22:6 (docosahexaenoic acid or DHA) is much higher in water extraction (57.55%), in comparison to the others where only 3.63% in PBS and 1.20% in methanol, and this difference is significant at p < 0.01. No DHA was detected in ethanol extractions. Subsequently, C18:1 (oleic acid) was only detected in PBS (21.98%) and water extraction (7.50%). It is interesting that palmitic acid, C16:() was higher in methanol (20.82%) and ethanol (2.18%), while 12.55% was detected in PBS and only 2.20% in water extraction: and again this was significantly different at p < 0.01. Although our results have shown that all four solvents were different in terms of their ability to extract fatty acids, the major component for tissue repair was well preserved. Probably this is one of the important precocious steps when working with a delicate sea cucumber, in both experimental and/or at the preparative stages. Freshness of the sea cucumber samples is important when undertaking this type of experiment. Finally, we believe that the local sea cucumber S. chloronotus contains all the fatty acids required to play a potential active role in tissue repair.
  3. Sharma JN, Uma K, Noor AR, Rahman AR
    Gen. Pharmacol., 1996 Jan;27(1):55-63.
    PMID: 8742494
    1. The kallikrein-kinin system has a significant role in regulating arterial blood pressure. 2. Reduced formation of the kinin compontents may cause hypertensive diseases. This is because of the fact that this system is responsible for vasodilatation, reduction in total peripheral resistance, natriuresis, diuresis, increasing renal blood flow and releasing various vasodilator agents. 3. Reduced kinin-kallikrein generation in hypertensive subjects may also be associated with genetic and environmental defects. 4. The kallikrein-kinin system when administered to hypertensive patients can lower their raised blood pressure to normotensive levels. 5. The mode of action of angiotensin-converting enzyme inhibitors principally may be dependent on the kinin system protection.
  4. Zaiton Z, Merican Z, Khalid BA, Mohamed JB, Baharom S
    Gen. Pharmacol., 1993 Jan;24(1):195-9.
    PMID: 8482496
    1. The mean levels of lipid peroxidation products, namely conjugated diene and malonaldehyde, were increased in the soleus muscles of hyperthyroid cats, while the mean glutathione peroxidase activity was decreased. No corresponding similar changes were noted in the fast extensor digitorum longus muscles and serum. 2. Propranolol administration prevented the increase in conjugated diene level in the soleus muscles of hyperthyroid cat but not the malonaldehyde level. It also prevented the reduction in glutathione peroxidase activity in the slow oxidative soleus muscles of hyperthyroid cats. 3. Maximal twitch tension, subtetanic tension and maximum tetanic tension of soleus and EDL muscles were reduced in hyperthyroid cats. Propranolol administration for 5 weeks to hyperthyroid cats did not prevent the reduction in tension of contractions of these muscles. 4. It is suggested that lipid peroxidation might not be responsible for the myopathy in hyperthyroidism and propranolol administration does not improve skeletal muscle function in hyperthyroid animals.
  5. Jais AM, Matori MF, Kittakoop P, Sowanborirux K
    Gen. Pharmacol., 1998 Apr;30(4):561-3.
    PMID: 9522175
    1. Fatty acid profiles in the external mucus extract and roe of Channa striatus were determined using gas chromatography (GC). 2. The mucus samples were collected by inducing hypothermic stress (-20 degrees C) for about 1 hr, and the roe were collected from gravid females at night soon after they liberated their eggs in a spawning program. 3. All mucus and roe samples were freeze-dried, except a part of roe which was not. 4. The mucus extract contained unsaturated fatty acid (oleic acid, C18:1 and linoleic acid, C18:2) as a major component, 21.25% and 22.47% of total lipid. 5. For the freeze- and nonfreeze-dried roe, the major components of fatty acid were somewhat similar to the mucus but with higher percentages: 58.56%, 26.08% and 45.76%, 20.94%. Interestingly, the nonfreeze-dried roe contained a large proportion of arachidic acid, C20:0 (22.16%), which was totally absent in the freeze-dried roe samples. 6. This profiling of the fatty acid mucus extract and roe is useful in strengthening the earlier claims that haruan possesses a potential remedy for wound healing (Mat Jais et al., 1994). Therefore, we are discussing the possibility of getting an optimum amount of the essential fatty acid for wound healing from various other parts of the fish without sacrificing the fish.
  6. Sharma JN, Wirth KJ
    Gen. Pharmacol., 1996 Jan;27(1):133-6.
    PMID: 8742510
    1. This study examines the effect of Hoe 140, a bradykinin (BK) 2 receptor antagonist, indomethacin and prednisolone on chronic adjuvant arthritis of the knee in rats. We also evaluated the influence of Hoe 140 on BK-forming enzymes in the synovial and paw tissues. 2. Adjuvant arthritis was induced in male Sprague-Dawley rats in the right knee by injecting 0.05 ml of a fine suspension of heat-killed Mycobacterium tubercle bacilli in liquid paraffin (5 mg/ml). 3. Hoe 140 (1.5 mg/kg i.p.), indomethacin (2.5 mg/kg orally) and prednisolone (3.0 mg/kg orally) administration for 9 days resulted in significant suppression of knee joint swelling. Plasma and tissue kallikrein levels were raised (P < 0.01) in the synovial and paw tissues of adjuvant arthritic rats. Hoe 140 treatment reduced (P < 0.05) tissue kallikrein but increased (P < 0.01) plasma kallikrein levels in synovial tissue. 4. Hoe 140 treatment did not alter (P > 0.05) the raised plasma and tissue kallikrein levels in the paw tissue. The findings indicate that Hoe 140 may be a useful anti-inflammatory agent and BK plays a major role in this adjuvant-induced arthritis model.
  7. Makpol S, Shamaan NA, Jarien Z, Top AG, Khalid BA, Wan Ngah WZ
    Gen. Pharmacol., 1997 Apr;28(4):589-92.
    PMID: 9147029
    1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.
  8. Nwe KH, Morat PB, Khalid BA
    Gen. Pharmacol., 1997 May;28(5):661-4.
    PMID: 9184798
    1. Sex steroids have been shown to regulate the biosynthesis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11 beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar rats was determined following a daily IM injection of sex steroids for 7 days. 4. The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T in normal and ADX rats. The enzyme activity in normal rats given both T and E2 was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The presence of corticosteroids influenced the effects of E2, but not of T and P4, on 11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4 increased it. E2 did not act through lowering T level.
  9. Ridzwan BH, Kaswandi MA, Azman Y, Fuad M
    Gen. Pharmacol., 1995 Nov;26(7):1539-43.
    PMID: 8690242
    1. Three species of sea cucumbers found in the Sabah coastal areas were screened for the presence of antibacterial activity using three methods of extraction. Tests were conducted in vitro using the agar absorption method. 2. Both the lipid extract and the methanol-solvent extract from Holothuria atra, Holothuria scabra and Bohadshia argus were found to show no antibacterial activity. 3. Phosphate-buffered saline (PBS) from H. atra and B. argus, however, inhibited the growth of all gram-positive and gram-negative bacteria. 4. Comparisons were also made between extracts from the outer layer of H. atra and its inner part, and it was found that the extract from the outer layer showed less bacterial growth inhibition property. 5. The bacterial growth inhibition property of the PBS extract from H. atra, however, is dependent on the extract's concentration. Bacterial growth inhibition was apparent after 48 hr incubation.
  10. Jais AM, McCulloch R, Croft K
    Gen. Pharmacol., 1994 Sep;25(5):947-50.
    PMID: 7835642
    1. Two species of snakehead fish are available in Sabah, i.e. Channa striatus and Channa melanosoma, and are commonly known as haruan. Haruan is consumed by many Malaysians to induce healing after a clinical operations. However, there is no scientific evidence as yet to substantiate the claim, and so it was decided to analyse the biochemical composition in haruan to determine which compounds may have a possible role or potential in wound healing. 2. Samples (midline fillet) of both species were extracted separately in hexane for the qualitative analysis of fatty acids by a gas chromatography, Hewlett-Packard 5890A, using a 10 meter superox 11 column (Alltech) at temperature between 190 and 245 degrees C. Peak areas were calculated automatically using Hewlett-Packard 3393A computing integrator. Subsequently, the amino acid composition was analysed using a precolumn derivatization reverse phase HPLC waters PICO-TAG system. 3. Haruan is found to contain unusually high arachidonic acid (AA) but almost no eicosapentaenoic acid (EPA). AA which is a precursor of prostaglandin may initiate blood clotting and be responsible for growth. Haruan also contains all the essential amino acids for wound healing, particularly glycine which is the most important component of human skin collagen. Therefore, haruan contained all the basic biochemical requirements for wound healing.
  11. Sharma JN
    Gen. Pharmacol., 1993 Mar;24(2):267-74.
    PMID: 8387049
    1. Bradykinin and related kinins may act on four types of receptors designated as B1, B2, B3 and B4. It seems that the B2 receptors are most commonly found in various vascular and non-vascular smooth muscles, whereas B1 receptors are formed in vitro during trauma, and injury, and are found in bone tissues. 2. These BK receptors are involved in the regulations of various physiological and pathological processes. 3. The mode of kinin actions are based upon the interactions between the kinin and their specific receptors, which can lead to activation of several second-messenger systems. 4. Recently, numerous BK receptors antagonists have been synthesized with prime aim to treat diseases caused by excessive kinin production. 5. These diseases are RA, inflammatory diseases of the bowel, asthma, rhinitis and sore throat, allergic reactions, pain, inflammatory skin disorders, endotoxin and anaphylactic shock and coronary heart diseases. 6. On the other hand, BK receptor antagonists could be contraindicated in hypertension, since these drugs may antagonize the antihypertensive therapy and/or may trigger the hypertensive crisis. 7. It is worth suggesting that the BK receptor agonists might be useful antihypertensive drugs.
  12. Nabishah BM, Morat PB, Kadir BA, Khalid BA
    Gen. Pharmacol., 1991;22(2):389-92.
    PMID: 1647349
    1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
  13. Sharma JN
    Gen. Pharmacol., 1988;19(2):177-87.
    PMID: 3280399
    The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.
  14. Ridzwan BH, Waton NG, Jais AM
    Gen. Pharmacol., 1989;20(2):133-6.
    PMID: 2565846
    1. Acid secretion for each dog has reached a near maximum (100%) at the 6th samples, 90 min after the intravenous infusion of histamine (10 mu ghr-1, or approximately equal to 0.3 mghr-1). 2. 0.5 mgkg-1 Cimetidine had produced a mean inhibition of 47% on the stomach. 3. 0.1 mgkg-1 Ranitidine (D 14,951) could only inhibit a maximum of 28%, and the secretion had return to normal in just 30 min. 4. 0.025 mgkg-1 Tiotidine (D 15,104) had inhibited 53% acid secretion within 15 min of exposure. Recovery was quite similar to that of Cimetidine, at 150 min. 5. At a dosage one fifth of Cimetidine (0.1 mgkg-1) D 15,144 had depressed 35% of acid secretion at the first 15 min. The inhibition is gradually increased to about 43% (at 30 min), and was maintained for the next 105 min.
  15. Ridzwan BH, Jais AM, Waton NG
    Gen. Pharmacol., 1988;19(4):631-6.
    PMID: 3410287
    1. 30 mg kg-1 chlorpromazine (CPZ) depleted more than half of the tissue histamine from lungs, stomach, ileum and skin of the normal guinea-pigs. However, the drug increased the tissue histamine content in scorbutic animals. 2. In contrast, reserpine depleted histamine from the four tested tissues in both normal and scorbutic animals, except those in the lungs of the control animals. 3. Ascorbic acid only depleted histamine from the stomach and ileum. 4. A 24 hr period was the time limit for CPZ to deplete the histamine in all the four tested tissues. 5. Histamine partially or completely recovered in the tissues after the next 24 hr.
  16. Nabishah BM, Merican Z, Morat PB, Alias AK, Khalid BA
    Gen. Pharmacol., 1990;21(6):935-8.
    PMID: 2177714
    1. Steroid hormones have been shown to regulate the concentration of adrenergic and muscarinic receptors in many tissues. 2. The cyclic adenosine 3',5'-monophosphate (cAMP) content in rat lung tissues in response to either dexamethasone, corticosterone, deoxycorticosterone or progesterone for 7 days were measured following intraperitoneal injection of isoprenaline just before sacrificed. 3. There was a significant increase in cAMP level (P less than 0.001) in dexamethasone and corticosterone-treated rats compared to controls that received isoprenaline alone. 4. Pretreatment with deoxycorticosterone and progesterone suppressed the increase in cAMP in response to isoprenaline. 5. The effect of glucocorticoids in causing bronchodilatation in asthmatic patients is partly due to the restoration of adenyl cyclase responsiveness to beta-agonist.
  17. Sharma JN
    Gen. Pharmacol., 1990;21(4):451-7.
    PMID: 2199299
    The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs.
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