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.
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.
Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.
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.
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.
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.
We studied the effect of indomethacin, a cyclooxygenase inhibitor, on bradykinin-induced responses in the intact and denuded epithelium of the isolated tracheal smooth muscle in guinea pigs. Epithelium removal alone did not alter the responsiveness to bradykinin. Indomethacin (2.8 microM) enhanced the sensitivity to bradykinin of both intact and denuded preparations. This finding suggests that the tracheal epithelial may have no protective effect on the contractile responses induced by bradykinin. This may be due to the presence of high amounts of bradykinin-inactivating enzymes in the tracheal smooth muscle. Indomethacin-medicated potentiation caused by bradykinin in epithelium intact and denuded preparations may be an indication of removal of the bronchodilator prostaglandin biosynthesis. The significance of these findings is discussed.
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.
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 present study aimed to evaluate the effect of Hoe 140, a BK receptor B(2) antagonist, on acute oedema induced by carrageenan, BK and kaolin in male Wistar Kyoto rats. Hoe 140 (0.2 mg/kg and 20 mg/kg) given ip caused significant (p<0.05 and p<0.01) inhibition of carrageenan and BK-induced paw oedema. This suggests that BK is the prime inflammatory mediator of carrageenan oedema, and that it is also a specific blocker of oedema caused by BK. Furthermore, Hoe 140 was found to be less effective in reducing kaolin-induced oedema in rats. This might reflect that BK is not a prime inflammatory mediator of kaolin-induced oedema. The possible significance of these findings is discussed.
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).
It is known that BK does play a role in the cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors. The present study therefore was conducted to examine the effects of bradykinin (BK) and its antagonist on survival time in spontaneously hypertensive rats (SHR) with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure (BP) in the presence and absence of BK and BK2 receptor antagonist, D-Arg-[Hyp-D-Phe7]BK. Coronary artery was ligated in anaesthetized rats and they were artificially ventilated with room air (stroke volume, 4 ml; 48 strokes/min) as described by the previous investigators. Lead II elecrocardiogram (ECG) was recorded from subcutaneous steel needle electrodes. Results of this investigation indicated that BK treatment 4 microg/kg (i.v.) and 8 microg/kg (i.v.) caused significant (P < 0.05) increase in survival time in SHR with coronary artery ligation for 15 min and continuously as compare to their respective saline-treated controls. However, BK antagonist treatment 4 microg/kg (i.v.) abolished the increase in survival time caused by BK treatment. The mean values of survival time between the saline-treated and BK antagonist plus BK-treated rats did not differ significantly (P > 0.05). The heart rate and BP responses were greatly reduced (P < 0.001) in the presence of coronary artery ligation. These findings suggest that BK might have cardioprotective effect to increase the survival time in rats by activating BK2 receptors after coronary artery ligation.
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 effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.
The present investigation evaluated the effects of aprotinin, an inhibitor of kallikrein, on blood pressure responses, heart rate, and duration of hypotension induced by acute administration of captopril and enalapril (angiotensin-converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats. Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a significant (p < 0.001) fall in systolic and diastolic blood pressures in the absence of aprotinin. In contrast, captopril (20 mg/kg) and enalapril (20 mg/kg) failed (p > 0.05) to cause a fall in systolic and diastolic blood pressures in the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as well as in the absence of aprotinin. The duration of hypotension produced by captopril and enalapril was abolished significantly (p < 0.001) in the presence of aprotinin. These findings may suggest that captopril and enalapril caused hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin can antagonize the hypotensive responses of these agents. Thus, kallikrein may be an independent mediator in the regulation of blood pressure.
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.
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.
Components of the kallikrein-kinin system are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B(2) receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI(2) and PAF) in the inflamed joint. B(2)-receptor antagonists may provide valuable agents as new analgesic drugs. Furthermore, it is suggested that substances to reduce activation of the kallikrein-kinin system (KKS) may provide a pharmacological basis for the synthesis of novel antirheumatic or anti-inflammatory drugs.
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.