The present investigation was aimed at evaluating the cardiac and total plasma kininogen levels, as well as LVWT in hypertensive and diabetic rats. STZ-induced diabetes produced a significant (P < 0.001) rise in mean arterial blood pressure (BP). The LVWT increased (P < 0.001) in SHR with and without diabetes) and diabetic WKYR. The cardiac tissue, as well as total plasma kininogen levels fell significantly (P < 0.001) in diabetic WKYR and SHR with and without diabetes compared to the control WKYR. These findings suggest that reduced kininogen levels may indicate a deficiency in kinin generation in the heart and in the peripheral circulation in diabetic and hypertensive rats. This effect may contribute to the development of LVH.
Crinum asiaticum Linn plant is used in Malaysia as a rheumatic remedy and to relieve local pain. In the present study, we examined the anti-inflammatory effects of this plant extract on carrageenan-induced hind paw oedema in mice. C. asiaticum was serially extracted with petroleum ether, followed by chloroform and lastly, methanol. The chloroform and methanol extracts of the plant given orally (50 mg kg-1) caused significant (p < 0.05; n = 7) reduction in paw oedema but the petroleum ether extract did not induce significant effect (p > 0.05) on paw oedema. The methanol extract was then dissolved in water and extracted consecutively with chloroform, ethyl acetate and butanol. The chloroform fraction of methanol extract (CFME) treatment (50 mg kg(-1)) significantly reduced (p < 0.05; n = 7) the acute paw oedema. This may indicate that active anti-inflammatory compounds are present in the CFME. In an attempt to study the mechanism of action of its anti-inflammatory activity, the effects of CFME on BK- and histamine-induced contractions were investigated in isolated rat uterus and guinea-pig ileum preparations, respectively. It was found that CFME caused dose-dependent reduction (p < 0.05; n = 6) of the contractile response induced by BK and shifted the log dose-response curve of histamine to the right. The present findings suggest that C. asiaticum possessed an anti-inflammatory activity as suggested by its use in traditional medicine. The anti-inflammatory activity of this plant could not have been due to its anti-bradykinin activities as CFME non-specifically inhibited BK-induced contraction. It also suggest that CFME may contain compound(s) with anti-histaminic properties. The significance of these findings is discussed.
The tubers of Amorphophallus paeoniifolius (Elephant foot yam), principally consumed as crop food and vegetables, are used in ethno-medicinal practices in mitigation of constipation and piles. Hence, present study evaluated the effect of tubers of A. paeoniifolius and its active constituents glucomannan and betulinic acid on experimentally-induced constipation. The tuber and its extracts were standardized as per Ayurvedic Pharmacopoeia of India and physicochemical constants were found within the pharmacopoeial limit. HPTLC fingerprint profile of extracts has been developed using suitable mobile phase. Methanolic extract was subjected to column chromatography. The isolated phytoconstituents were characterized by FT-IR, NMR and MS and identified as betulinic acid and β-sitosterol. Functional constipation was induced in rats by oral administration of loperamide (3 mg/kg) for first 3 consecutive days. The rats were orally treated with methanolic and aqueous tuber extracts in the doses of 125, 250 and 500 mg/kg, glucomannan (300 mg/kg) and betulinic acid (1.5 mg/kg) for 7 days. The parameters viz. number of stools, wet weight of stools and moisture content of stools and intestinal transit were studied. Treatment with tuber extracts, glucomannan and betulinic acid showed significant (p < 0.05) increase in fecal parameters and intestinal transit in constipated rats. The effects were comparable to standard laxative drug, sodium picosulfate (5 mg/kg, orally). The results indicated that tuber extracts and its active constituents showed laxative effect and relieved constipation. It is concluded that tuber of A. paeoniifolius exhibited beneficial effect in functional constipation possibly through its laxative action. The study validates its ethno-medicinal use in correction of constipation. The principal constituents, betulinic acid and glucomannan in tuber extracts might have played important role in relieving the constipation.
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.
This study examined the effects of streptozotocin-induced diabetes on blood pressure and cardiac tissue kallikrein levels in WKYR and SHR. Streptozotocin-induced diabetes caused significant (p < 0.001) increase in SBP and DBP in WKYR and SHR as compared with their respective controls. We also observed that the active cardiac tissue kallikrein levels reduced greatly (p < 0.001) in diabetic WKYR and SHR than the normal rats. These findings suggest for the first time that the cardiac tissue kallikrein formation may have a greater role in the regulation of blood pressure and cardiac function.
Though Chromobacterium violaceum is a common inhabitant of soil and water in tropical and sub-tropical regions, human infections are rare but when they do occur result in high mortality. Since the first case from Malaysia in 1927, about 150 cases have been reported in world literature. Till date 6 cases have been reported from southern and eastern parts of India. We report here a case of C. violaceum septicaemia, probably the first case from north India. The patient, a 6 and a half year old boy was admitted with high fever. The patient had anaemia, neutrophilic leucocytosis and bilateral chest infiltrates. Routine and bacteriological investigations were carried out to establish the aetiological diagnosis. C. violaceum was isolated in pure culture from blood and pus. The patient was successfully treated with ciprofloxacin and amikacin. This is probably the first documented case report of C. violaceum infection from north India and the only Indian case with septicaemia which survived.
Tor tor is an important game and food fish of India with a distribution throughout Asia from the trans-Himalayan region to the Mekong River basin to Malaysia, Pakistan, Bangladesh and Indonesia. A new cell line named TTCF was developed from the caudal fin of T. tor for the first time. The cell line was optimally maintained at 28°C in Leibovitz-15 (L-15) medium supplemented with 20% fetal bovine serum (FBS). The propagation of TTCF cells showed a high plating efficiency of 63.00%. The cytogenetic analysis revealed a diploid count of 100 chromosomes at passage 15, 30, 45 and 60 passages. The viability of the TTCF cell line was found to be 72% after 6 months of cryopreservation in liquid nitrogen (-196°C). The origin of the cell lines was confirmed by the amplification of 578- and 655-bp sequences of 16S rRNA and cytochrome oxidase subunit I (COI) genes of mitochondrial DNA (mtDNA) respectively. TTCF cells were successfully transfected with green fluorescent protein (GFP) reporter plasmids. Further, immunocytochemistry studies confirm its fibroblastic morphology of cells. Genotoxicity assessment of H₂O₂ in TTCF cell line revealed the utility of TTCF cell line as in vitro model for aquatic toxicological studies.
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.
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).
Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetomella pseudocircinoseta and Coniella pseudodiospyri on Eucalyptus microcorys leaves, Cladophialophora eucalypti, Teratosphaeria dunnii and Vermiculariopsiella dunnii on Eucalyptus dunnii leaves, Cylindrium grande and Hypsotheca eucalyptorum on Eucalyptus grandis leaves, Elsinoe salignae on Eucalyptus saligna leaves, Marasmius lebeliae on litter of regenerating subtropical rainforest, Phialoseptomonium eucalypti (incl. Phialoseptomonium gen. nov.) on Eucalyptus grandis × camaldulensis leaves, Phlogicylindrium pawpawense on Eucalyptus tereticornis leaves, Phyllosticta longicauda as an endophyte from healthy Eustrephus latifolius leaves, Pseudosydowia eucalyptorum on Eucalyptus sp. leaves, Saitozyma wallum on Banksia aemula leaves, Teratosphaeria henryi on Corymbia henryi leaves. Brazil, Aspergillus bezerrae, Backusella azygospora, Mariannaea terricola and Talaromyces pernambucoensis from soil, Calonectria matogrossensis on Eucalyptus urophylla leaves, Calvatia brasiliensis on soil, Carcinomyces nordestinensis on Bromelia antiacantha leaves, Dendryphiella stromaticola on small branches of an unidentified plant, Nigrospora brasiliensis on Nopalea cochenillifera leaves, Penicillium alagoense as a leaf endophyte on a Miconia sp., Podosordaria nigrobrunnea on dung, Spegazzinia bromeliacearum as a leaf endophyte on Tilandsia catimbauensis, Xylobolus brasiliensis on decaying wood. Bulgaria, Kazachstania molopis from the gut of the beetle Molops piceus. Croatia, Mollisia endocrystallina from a fallen decorticated Picea abies tree trunk. Ecuador, Hygrocybe rodomaculata on soil. Hungary, Alfoldia vorosii (incl. Alfoldia gen. nov.) from Juniperus communis roots, Kiskunsagia ubrizsyi (incl. Kiskunsagia gen. nov.) from Fumana procumbens roots. India, Aureobasidium tremulum as laboratory contaminant, Leucosporidium himalayensis and Naganishia indica from windblown dust on glaciers. Italy, Neodevriesia cycadicola on Cycas sp. leaves, Pseudocercospora pseudomyrticola on Myrtus communis leaves, Ramularia pistaciae on Pistacia lentiscus leaves, Neognomoniopsis quercina (incl. Neognomoniopsis gen. nov.) on Quercus ilex leaves. Japan, Diaporthe fructicola on Passiflora edulis × P. edulis f. flavicarpa fruit, Entoloma nipponicum on leaf litter in a mixed Cryptomeria japonica and Acer spp. forest. Macedonia, Astraeus macedonicus on soil. Malaysia, Fusicladium eucalyptigenum on Eucalyptus sp. twigs, Neoacrodontiella eucalypti (incl. Neoacrodontiella gen. nov.) on Eucalyptus urophylla leaves. Mozambique, Meliola gorongosensis on dead Philenoptera violacea leaflets. Nepal, Coniochaeta dendrobiicola from Dendriobium lognicornu roots. New Zealand, Neodevriesia sexualis and Thozetella neonivea on Archontophoenix cunninghamiana leaves. Norway, Calophoma sandfjordenica from a piece of board on a rocky shoreline, Clavaria parvispora on soil, Didymella finnmarkica from a piece of Pinus sylvestris driftwood. Poland, Sugiyamaella trypani from soil. Portugal, Colletotrichum feijoicola from Acca sellowiana. Russia, Crepidotus tobolensis on Populus tremula debris, Entoloma ekaterinae, Entoloma erhardii and Suillus gastroflavus on soil, Nakazawaea ambrosiae from the galleries of Ips typographus under the bark of Picea abies. Slovenia, Pluteus ludwigii on twigs of broadleaved trees. South Africa, Anungitiomyces stellenboschiensis (incl. Anungitiomyces gen. nov.) and Niesslia stellenboschiana on Eucalyptus sp. leaves, Beltraniella pseudoportoricensis on Podocarpus falcatus leaf litter, Corynespora encephalarti on Encephalartos sp. leaves, Cytospora pavettae on Pavetta revoluta leaves, Helminthosporium erythrinicola on Erythrina humeana leaves, Helminthosporium syzygii on a Syzygium sp. bark canker, Libertasomyces aloeticus on Aloe sp. leaves, Penicillium lunae from Musa sp. fruit, Phyllosticta lauridiae on Lauridia tetragona leaves, Pseudotruncatella bolusanthi (incl. Pseudotruncatellaceae fam. nov.) and Dactylella bolusanthi on Bolusanthus speciosus leaves. Spain, Apenidiella foetida on submerged plant debris, Inocybe grammatoides on Quercus ilex subsp. ilex forest humus, Ossicaulis salomii on soil, Phialemonium guarroi from soil. Thailand, Pantospora chromolaenae on Chromolaena odorata leaves. Ukraine, Cadophora helianthi from Helianthus annuus stems. USA, Boletus pseudopinophilus on soil under slash pine, Botryotrichum foricae, Penicillium americanum and Penicillium minnesotense from air. Vietnam, Lycoperdon vietnamense on soil. Morphological and culture characteristics are supported by DNA barcodes.
We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.
We have investigated the effect of indomethacin on histamine- and acetylcholine (ACh)-induced responses in the intact and denuded epithelium of guinea pig isolated tracheal smooth muscle. Epithelium removal resulted in increased responsiveness to ACh and histamine. Indomethacin (2.8 microM) enhanced the sensitivity of both intact and denuded preparations to histamine and ACh. These findings suggest that the tracheal epithelium of guinea pig plays a protective role against bronchoconstrictors, such as ACh and histamine. Furthermore, indomethacin-mediated hyperresponsiveness caused by these agonists in epithelium denuded preparations might be a reflection of removal of prostaglandin (PG) biosynthesis. A similar process of interaction in indomethacin-treated asthmatic patients (with damaged airway epithelium) might take place. The significance of these findings is discussed.
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.
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.
Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.
We investigated the cardiac tissue kallikrein and kininogen levels, left ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and spontaneously hypertensive rats with and without streptozotocin-induced diabetes. The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto diabetic and spontaneously hypertensive diabetic rats as compared with their respective controls. The cardiac tissue kallikrein and kininogen levels were reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto control rats. In addition, the left ventricular thickness was found to be increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats in the presence and in the absence of diabetes. Our results indicate that reduced activity of the kinin-forming system may be responsible for inducing left ventricular hypertrophy in the presence of raised mean arterial blood pressure in diabetic and hypertensive rats. Thus, the kinin-forming components might have a protective role against the development of left ventricular hypertrophy. The possible significance of these findings is discussed.
Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.