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1.
BMC Infect Dis ; 23(1): 579, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670240

RESUMO

BACKGROUND AND OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is the second leading cause of community-acquired and hospital-acquired gram-negative bloodstream infection (BSI). This study aimed to assess the epidemiological and microbial-resistance characteristics and clinical factors associated with K. pneumoniae BSI in Saudi Arabia. MATERIALS AND METHODS: Data of 152 K. pneumoniae isolates diagnosed between January 2019 and January 2020 at King Fahad Medical City, Riyadh, Saudi Arabia were evaluated retrospectively. Clinical records of the patients were collected and analysed statistically. RESULTS: In total, 152 cases of K. pneumoniae BSI were identified. Adult patients (66.4%) were at a higher risk of developing the infection than paediatric patients (33.6%). The rate of infection was slightly higher in women than in men. Neurological disorders were the predominant underlying conditions for the acquisition of K. pneumoniae BSI, at all ages. Most of the deceased patients were adults with multi-organ dysfunction. Klebsiella pneumoniae showed disturbing resistance to amoxicillin-clavulanate and cefuroxime (72.4%), ceftazidime (67.8), cephalothin (76.3%), and to Carbapenems (36.1%). CONCLUSIONS: The impact of K. pneumoniae BSI was seen not only at the patient level, but also at the community level, and was related to multi-drug resistant infection. These findings provide a better understanding of microbial resistance and its association with patient clinical outcomes.


Assuntos
Bacteriemia , Infecções por Klebsiella , Klebsiella pneumoniae , Adulto , Criança , Feminino , Humanos , Masculino , Anti-Infecciosos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita/epidemiologia , Resultado do Tratamento , Testes de Sensibilidade Microbiana
2.
Molecules ; 28(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37570720

RESUMO

The incorporation of fermented camel milk with natural additives possesses numerous benefits for the treatment of various pathological and metabolic conditions. The present study investigated the impact of fortification of fermented camel milk with sage or mint leaves powder (1 and 1.5%, respectively) on glucose and insulin levels, lipid profile, and liver and kidney functions in alloxan-induced diabetic rats. The gross chemical composition of sage and peppermint leaves powder was studied. The chemical composition of sage and mint extracts was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS) of sage and mint extracts. Furthermore, a total of forty-two adult normal male albino rats were included in this study, whereas one group was kept as the healthy control group (n = 6 rats) and diabetes was induced in the remaining animals (n = 36 rats) using alloxan injection (150 mg/kg of body weight). Among diabetic rats groups, a control group (n = 6 rats) was kept as the diabetic control group whereas the other 5 groups (6 rats per group) of diabetic rats were fed fermented camel milk (FCM) or fermented camel milk fortified with 1 and 1.5% of sage or mint leaves powder. Interestingly, the oral administration of fermented camel milk fortified with sage or mint leaves powder, at both concentrations, caused a significant decrease in blood glucose level and lipid profile, and an increase in insulin level compared to the diabetic control and FCM groups. Among others, the best results were observed in the group of animals that received fermented camel milk fortified with 1.5% sage powder. In addition, the results revealed that the fermented camel milk fortified with sage or mint leaves powder improved the liver and kidney functions of diabetic rats. Our study concluded that the use of sage and mint leaves powder (at a ratio of 1.5%) with fermented camel milk produces functional food products with anti-diabetic activity.


Assuntos
Diabetes Mellitus Experimental , Insulinas , Mentha , Salvia officinalis , Ratos , Masculino , Animais , Leite/química , Mentha piperita , Salvia officinalis/química , Camelus , Pós/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Aloxano , Mentha/química , Lipídeos/análise , Folhas de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/análise
3.
Medicina (Kaunas) ; 59(8)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37629715

RESUMO

Background and Objectives: Early detection of neonatal sepsis is critical because it is potentially fatal. Therefore, sepsis biomarkers of sufficient sensitivity and specificity are needed. This study aimed to evaluate the utility of peripheral blood parameters as neonatal sepsis biomarkers and the diagnostic performance of the monocyte distribution width (MDW) in sepsis in a neonatal intensive care unit. Materials and Methods: A cross-sectional study was conducted from September 2019 to August 2020 at the King Saud University Medical City in Riyadh, Saudi Arabia. Samples were collected and organised as follows: 77 study cases were subdivided into two subgroups (other health complication (49) and sepsis (28)), and there were 70 controls. The causative microorganisms of neonatal sepsis were isolated. Peripheral blood samples were collected from each neonate in an ethylenediaminetetraacetic acid tube for a complete blood count and a leukocyte differential count. Moreover, the receiver operating characteristic (ROC) curve analysis was used to measure the diagnostic performance of the MDW. Results: The haematological parameters and neonatal sepsis cases had a considerable correlation. The MDW was the most significant haematological parameter. The ROC analysis of the MDW demonstrated that the area under the curve was 0.89 (95% confidence interval: 0.867 to 0.998) with a sensitivity of 89.3%, a specificity of 88.2%, and a negative predictive value of 97.2% at the cut-off point of 23. Conclusions: The use of haematological parameters is feasible and can be performed rapidly. Neonatal sepsis showed a strong correlation with leukopenia, anaemia, thrombocytopenia, and an elevated MDW value. Moreover, the ROC curve analysis confirmed the high diagnostic ability of the MDW in neonatal sepsis prediction.


Assuntos
Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Sepse Neonatal/diagnóstico , Estudos Transversais , Monócitos , Sepse/diagnóstico , Biomarcadores
4.
Medicina (Kaunas) ; 58(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36556974

RESUMO

Background and Objectives: In pre-eclampsia, restricted blood supply due to the lack of trophoblastic cell invasion and spiral artery remodeling is responsible for adverse pregnancies and maternal outcomes, which is added to by maternal undernutrition. This study was designed to observe the effect of multiple nutritional micronutrient supplements on the pregnancy outcomes of underweight pre-eclamptic women. To investigate the effects of lipid-based multiple micr supplementations (LNS-PLW) on pregnancy and maternal outcomes in underweight primigravida pre-eclamptic women. Materials and Methods: A total of 60 pre-eclamptic, underweight primigravida women from the antenatal units of tertiary care hospitals in the Khyber Pakhtunkhwa Province, Pakistan, were randomly divided into two groups (Group 1 and Group 2). The participants of both groups were receiving routine treatment for pre-eclampsia: iron (60 mgs) and folic acid (400 ug) IFA daily. Group 2 was given an additional sachet of 75 gm LNS-PLW daily till delivery. The pregnancy outcomes of both groups were recorded. The clinical parameters, hemoglobin, platelet count, and proteinuria were measured at recruitment. Results: The percentage of live births in Group 2 was 93% compared to 92% in Group 1. There were more normal vaginal deliveries (NVDs) in Group 2 compared to Group 1 (Group 2, 78% NVD; group 1, 69% NVD). In Group 1, 4% of the participants developed eclampsia. The frequency of cesarean sections was 8/26 (31%) in Group 1 and 6/28 (22%) in Group 2. The number of intrauterine deaths (IUDs) was only 1/28 (4%) in Group 2, while it was 2/26 (8%) in Group 1. The gestational age at delivery significantly improved with LNS-PLW supplementation (Group 2, 38.64 ± 0.78 weeks; Group 1, 36.88 ± 1.55 weeks, p-value 0.006). The Apgar score (Group 2, 9.3; Group 1, 8.4) and the birth weight of the babies improved with maternal supplementation with LNS-PLW (Group 2, 38.64 ± 0.78 weeks: Group 1, 36.88 ± 1.55; p-value 0.003). There was no significant difference in systolic blood pressure, while diastolic blood pressure (Group 2, 89.57 ± 2.08 mmHg; Group 1, 92.17 ± 5.18 mmHg, p-value 0.025) showed significant improvement with LNS-PLW supplementation. The hemoglobin concentration increased with the LNS-PLW supplement consumed in Group 2 (Group 2, 12.15 ± 0.78 g/dL; Group 1, 11.39 ± 0.48 g/dL, p-value < 0.001). However, no significant difference among the platelet counts of the two groups was observed. Conclusions: The pregnancy and maternal outcomes of underweight pre-eclamptic women can be improved by the prenatal daily supplementation of LNS-PLW during pregnancy, along with IFA and regular antenatal care and follow-up.


Assuntos
Pré-Eclâmpsia , Lactente , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Magreza/induzido quimicamente , Resultado da Gravidez , Ácido Fólico/uso terapêutico , Suplementos Nutricionais , Micronutrientes/uso terapêutico , Lipídeos
5.
Int J Mol Sci ; 20(4)2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30823534

RESUMO

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2⁻related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Myristica/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Heme Oxigenase (Desciclizante)/genética , Masculino , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Silimarina/farmacologia , Silimarina/uso terapêutico
6.
Microb Pathog ; 117: 299-303, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29496525

RESUMO

Malaria is a harmful disease affecting both tropical and subtropical countries and causing sometimes fatal complications. The effects of malaria-related complications on the intestine have been relatively neglected, and the reasons for the intestinal damage caused by malaria infection are not yet clear. The present study aims to evaluate the influence of intestinal vitamin D receptor on host-pathogen interactions during malaria induced in mice by Plasmodium chabaudi. To induce the infection, animals were infected with 106P. chabaudi-parasitized erythrocytes. Mice were sacrificed on day 8 post-infection. The infected mice experienced a significant body weight loss and parasitaemia affecting about 46% of RBCs. Infection caused marked pathological changes in the intestinal tissue indicated by shortening of the intestine and villi. Moreover, the phagocytic activity of macrophages increased significantly (P < 0.01) in the infected villi compared to the non-infected ones. Infection by the parasite also induced marked upregulation of nuclear factor-kappa B, inducible nitric oxide synthase, Vitamin D Receptor, interleukin-1ß, tumour necrosis factor alpha and interferon gamma-mRNA. It can be implied from this that vitamin D receptor has a role in regulating malarial infection.


Assuntos
Interações Hospedeiro-Parasita/fisiologia , Mucosa Intestinal/metabolismo , Malária/sangue , Malária/complicações , Plasmodium chabaudi/patogenicidade , Receptores de Calcitriol/fisiologia , Animais , Peso Corporal , Modelos Animais de Doenças , Eritrócitos/parasitologia , Eritrócitos/patologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Parasita/genética , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Intestinos/parasitologia , Intestinos/patologia , Macrófagos/metabolismo , Malária/parasitologia , Malária/patologia , Camundongos , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Parasitemia , Fagocitose , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/metabolismo
7.
Microb Pathog ; 110: 409-413, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28705749

RESUMO

Helminth infections in general and digenetic trematodes in particular cause a huge economic loss globally to our livestock. Gigantocotyle explanatum is a digenetic amphistome that infects the bile ducts of water buffalo and are highly prevalent in tropical and sub-tropical countries. In the present study, effects of an organophosphate compound, Metrifonate (MF) in three doses, viz., 9.4 × 10-5 M (Dose I), 14.4 × 10-5 M (Dose II), and 19.4 × 10-5 M (Dose III), have been studied in vitro, on the motility and on some enzymatic and non-enzymatic oxidative stress indices in G. explanatum. The worm's motility and their non-enzymatic oxidative stress biomarkers like lipid peroxides measured as thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) were disrupted significantly in a dose-dependent manner. However, the enzymatic oxidative stress biomarkers like glutathione-S-transferase (GST) and superoxide dismutase (SOD) were affected by MF treatment in a biphasic manner. Exposure to Dose I significantly stimulated the activities of both GST and SOD, whereas exposure to Doses II and III resulted into significant inhibition in a dose-dependent manner. Our findings suggest that MF has potential to be a strong and effective anthelmintic, however, further studies in vitro as well as in vivo are needed to explore further these observations and understand the exact mode of MF action in G. explanatum and other trematodes of veterinary economic importance.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Trematódeos/efeitos dos fármacos , Triclorfon/farmacologia , Animais , Ductos Biliares/parasitologia , Biomarcadores , Búfalos/parasitologia , Glutationa/metabolismo , Glutationa Transferase/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Proteínas Recombinantes , Superóxido Dismutase/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Trematódeos/enzimologia , Trematódeos/isolamento & purificação , Triclorfon/administração & dosagem
8.
Microb Pathog ; 107: 69-74, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28336326

RESUMO

The development and spread of multidrug-resistant strains of malarial parasites have led to an overwhelming increase in the resistance to current antimalarial drugs. The urgent need for alternative antimalarial drugs has directed some of the current studies toward folkloric medicine approaches. Interestingly, the Zizyphus spina Cristi leaf extract (ZLE) has been found to exhibit antiplasmodial activity. This study evaluated the protective effect of ZLE against Plasmodium berghei-induced cerebral tissue injuries in mice. Male C57Bl/6 mice received an injection of P. berghei-infected red blood cells. Mice were divided into three groups (control, infected, and ZLE-treated), and were subjected to histological, biochemical, and molecular analyses. Murine malaria infections induced significant weight loss; however, upon ZLE treatment, the weight of mice was markedly restored. Additionally, infected mice showed brain histopathological changes and induction of oxidative damage. Significantly, ZLE treatment restored the levels of oxidative markers and antioxidant enzyme to the normal ranges. The mRNA expression of several genes in the brain of mice including Cacnb4, Adam23, Glrb, Vdac3, and Cabp1 was significantly upregulated during P. berghei infection. In contrast, ZLE markedly reduced the mRNA expression of these genes. To conclude, the results indicate that ZLE could play an important role in reducing the destructive effect of P. berghei-induced cerebral malaria owing to its antiplasmodial and antioxidant activities.


Assuntos
Antimaláricos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Malária Cerebral/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ziziphus/química , Proteínas ADAM/genética , Animais , Antioxidantes , Encéfalo/patologia , Encéfalo/fisiopatologia , Canais de Cálcio/genética , Proteínas de Ligação ao Cálcio/genética , Modelos Animais de Doenças , Malária/tratamento farmacológico , Malária/parasitologia , Malária Cerebral/sangue , Malária Cerebral/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas do Tecido Nervoso/genética , Folhas de Planta/química , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/patogenicidade , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Receptores de Glicina/genética , Regulação para Cima , Canais de Ânion Dependentes de Voltagem/genética
9.
Parasitol Res ; 115(4): 1427-33, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26670312

RESUMO

Malaria is a health burden disease where the world harnessed the power of expertise and innovation to understand the biology of the parasite and the pathogenesis of the disease as well as to discover effective drugs. However, the treatment of malaria remains a challenging task and inadequate to address today's perplexing problem, the emergence of resistant strains. Historically, traditional medicine has been a mainstay for remediation and still retains its importance with the presence of potent natural products. Pomegranate has been used as antioxidant and anti-inflammatory against a range of diseases. Therefore, pomegranate peel extract (PPE) was used in this study to examine its effect on Plasmodium chabaudi-induced hepatic inflammation. Animals were allocated into three groups: a vehicle control group, a group infected with 10(6) P. chabaudi-parasitized erythrocytes and a pomegranate-treated group infected with 10(6) P. chabaudi-parasitized erythrocytes. This group received 100 µl of 300 mg/kg PPE after infection. The results showed the effectiveness of PPE on reversing the anaemic signs that have been provoked by P. chabaudi infection through instating the haemoglobin concentration and erythrocyte count back to normal values. Moreover, PPE exhibited hepatoprotective activities upon histopathological examination and liver function tests. These data were further confirmed by the significant reduction of the hepatic oxidative markers, glutathione, nitric oxide and malondialdehyde, in mice infected with P. chabaudi. Based on these outcomes, pomegranate could be used as a hepatoprotective agent against P. chabaudi-induced hepatic injury. However, further studies are needed in order to determine the mode of action of pomegranate upon infection.


Assuntos
Hepatopatias/parasitologia , Lythraceae/química , Malária/complicações , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Fígado/patologia , Hepatopatias/prevenção & controle , Malária/tratamento farmacológico , Malondialdeído , Camundongos , Óxido Nítrico/farmacologia , Fitoterapia , Extratos Vegetais/química , Plasmodium chabaudi
10.
BMC Complement Altern Med ; 16: 221, 2016 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-27422638

RESUMO

BACKGROUND: Multiple drug-resistant malaria parasites have been widely detected, which has encouraged research studies focused on discovering alternative therapies. Medicinal plants such as pomegranate, Punica granatum, have been proven to exhibit antiprotozoal effects and therefore, we examined its effects on murine malaria-induced splenic injury and oxidative stress in this study. METHODS: Mice were divided into three groups, a vehicle control and two groups that were infected with 10(6) Plasmodium chabaudi-parasitized red blood cells (RBCs). The third group was gavaged with 100 µL of 300 mg/kg pomegranate peel extract for 6 days. All mice were euthanized on day 6 post-infection. RESULTS: The results revealed the potential antimalarial, antioxidant, and anti-inflammatory effects of pomegranate. Furthermore, pomegranate peel extracts significantly reduced parasitemia and spleen index of the treated mice compared to the untreated group. Additionally, the spleen histology score supported the findings by showing better amelioration in the pomegranate-treated mice than in the untreated mice. Concomitantly, the spleen capsule thickness showed clear evidence of splenomegaly in the untreated mice, as evidenced by the reduced spleen capsule. However, pomegranate peel extract exhibited a remarkable restorative effect on the spleen capsules of the treated mice. Moreover, the extract significantly reduced the expression levels of the proinflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as inducible nitric oxide synthase (iNOS). Moreover, our study showed that pomegranate extract profoundly affected oxidative stress levels by reducing the oxidant molecules, nitric oxide (NO) and malondialdehyde (MDA). CONCLUSION: This study showed that pomegranate clearly induced antimalarial activity in the host by attenuating inflammatory and oxidative stress responses. Furthermore, pomegranate enhanced the innate immune responses and, therefore, could serve an alternative therapy to control clinical malaria episodes and may protect against malaria infection.


Assuntos
Apoptose/efeitos dos fármacos , Lythraceae/química , Estresse Oxidativo/efeitos dos fármacos , Plasmodium chabaudi , Baço/efeitos dos fármacos , Animais , Imuno-Histoquímica , Malária , Masculino , Camundongos , Baço/parasitologia , Baço/fisiopatologia
11.
Proc Natl Acad Sci U S A ; 109(21): 8298-303, 2012 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-22566611

RESUMO

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc(1). Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria.


Assuntos
Antimaláricos/farmacologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Piridinas/farmacologia , Quinolonas/farmacologia , Animais , Antimaláricos/química , Células Cultivadas , Transporte de Elétrons/efeitos dos fármacos , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Hepatócitos/citologia , Hepatócitos/parasitologia , Macaca mulatta , Malária Falciparum/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos , Mitocôndrias/efeitos dos fármacos , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium cynomolgi/efeitos dos fármacos , Plasmodium cynomolgi/crescimento & desenvolvimento , Plasmodium falciparum/crescimento & desenvolvimento , Piridinas/química , Quinolonas/química
12.
Exp Parasitol ; 145: 80-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25102435

RESUMO

Multidrug resistant Plasmodium falciparum is the major health problem in the tropics. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate antimalarial activities of Garcinia mangostana Linn. crude ethanolic extract including its bioactive compounds as well as the metabolic footprinting of P. falciparum following exposure to G. mangostana Linn. extract. The median (range) IC50 (concentration that inhibits parasite growth by 50%) values of ethanolic extract of G. mangostana Linn., α-mangostin, ß-mangostin, gartanin, 9-hydroxycarbaxathone, artesunate, and mefloquine for 3D7 vs K1 P. falciparum clones were 12.6 (10.5-13.2) vs 4.5 (3.5-6.3) µg/ml, 7.3 (7.1-8.5) vs 5.0 (3.7-5.9) µg/ml, 47.3 (46.8-54.0) vs 35.0 (30.0-43.7) µg/ml, 9.2 (8.1-11.9) vs 6.8 (6.2-9.1) µg/ml, 0.6 (0.4-0.8) vs 0.5 (0.4-0.7) µg/ml, 0.4 (0.2-1.2) vs 0.7 (0.4-1.0)ng/ml, and 5.0 (4.2-5.0) vs 2.7 (2.5-4.6) ng/ml, respectively. The action of G. mangostana Linn. started at 12 h of exposure, suggesting that the stage of its action is trophozoite. The 12-h exposure time was used as a suitable exposure time for further analysis of P. falciparum footprinting. G. mangostana Linn. extract was found to target several metabolic pathways particularly glucose and TCA metabolisms. The malate was not detected in culture medium of the exposed parasite, which may indirectly imply that the action of G. mangostana Linn. is through interruption of TCA metabolism.


Assuntos
Antimaláricos/farmacologia , Garcinia mangostana/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Artemisininas/farmacologia , Artesunato , Resistência a Múltiplos Medicamentos , Glucose/metabolismo , Concentração Inibidora 50 , Mefloquina/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Plasmodium falciparum/metabolismo , Xantonas/farmacologia
13.
J Trop Med ; 2024: 8529788, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576602

RESUMO

Introduction: This study determines the incidence of common viral and helminth coinfections with malaria in the tertiary care hospital set up in southern Khyber Pakhtunkhwa, Pakistan. Materials and Methods: The multidimensional research included malaria patients admitted to different hospitals of district Kohat during January and December 2021. Stool samples and blood were assembled from the patients. Giemsa-stained microscopy-positive samples were processed by the immunochromatography technique (ICT) to identify Plasmodium species. Common viral infections such as viral hepatitis (A, B, and C), HIV, and dengue (DENV) were analyzed by ICT kits while SARS-CoV-2 was confirmed through real-time PCR. Furthermore, the intestinal helminths were identified using the Kato-Katz thick smear method. Results: Among 1278 patients, 548 were diagnosed with malaria, 412 (75.2%) were positive for P. vivax infection, 115 (21%) for P. falciparum, and 21 (3.8%) for mixed malaria infection (P. vivax/P. falciparum), with a higher incidence among males (65.2%) than females (34.8%). Coinfection with helminths was positive in 215 (39.3%) malaria patients. The most common infections were caused by the Ascaris lumbricoides species (42.6%) followed by Enterobius vermicularis (31.7%) and hookworm. A total of 24.6% of malaria-positive cases were also coinfected with different viruses with higher frequencies of confection for HAV (8.2%) and DENV (6.2%), respectively. The patients revealed higher incidence of coinfections with P. falciparum (57%) as compared with P. vivax (39.2%) and mixed infections (3.7%). Conclusion: This study demonstrated that the study population exhibited a significant incidence of coinfections with intestinal helminth and viral malaria.

14.
Infect Drug Resist ; 17: 571-581, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375102

RESUMO

Background: Proteus mirabilis (P. mirabilis) is known to cause various infections, most commonly urinary tract infections, and is a threat to hospitalized patients, especially in long-stay departments that utilize invasive devices. This study aims to fill the knowledge gap regarding P. mirabilis epidemiology and antimicrobial resistance in Saudi Arabia. It investigates epidemiological patterns, resistance characteristics, and clinical outcomes among P. mirabilis patients at King Fahad Medical City in Riyadh from 2019 to 2021. Methods: A total of 598 P. mirabilis isolated from diverse clinical specimens, including the clinical information of 78 intensive care unit (ICU) patients, were included in the current study. The Phoenix BD instrument was used for complete identification and sensitivity testing of Proteus spp. Demographic, clinical, and outcome data were reported and compared using statistical analysis. Results: Pan-drug-resistant isolates were identified in 2019 (n = 6), although multi- and extensively drug-resistant isolate frequencies were greatest among all patients in 2019. The highest susceptibility levels were observed for piperacillin-tazobactam, carbapenems, and cephalosporins antibiotics. In contrast, Cephalothin, trimethoprim-sulfamethoxazole, and ampicillin had the lowest susceptibilities. Urine infections with a positive culture of P. mirabilis were significantly higher in females and non-ICU patients (p <0.001), but respiratory infections were significantly higher in ICU patients (p <0.001). Moreover, ICU patients infected with P. mirabilis and undergoing renal dialysis have a 7.2-fold (P 0.034) higher risk of death than those not receiving dialysis. Conclusion: Hospitalized patients are at risk of fatal consequences due to P. mirabilis infection. It is crucial to conduct further investigation to fully understand the severity of this issue and take necessary measures to prevent it.

15.
ACS Omega ; 9(1): 166-177, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222566

RESUMO

Proper management and control measurements are needed to stop the spread of highly pathogenic E. coli isolates that cause urinary tract infections (UTI) by developing new antibacterial agents to ensure the safety of public health. Therefore, the present investigations were used to achieve the synthesis of iron oxide nanoparticles (IONPs) via a simple coprecipitation method using ferric nitrates Fe (NO3)3 as the precursor and hydrazine solution as the precipitator and to explore the antibacterial activity against eradicating Uropathogenic Escherichia coli (E. coli). The synthesized IONPs were further studied using a UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopic (SEM) analysis. The maximum surface plasmon resonance peak was observed as absorption at 320 nm in a colloidal solution to validate the synthesis of IONPs. The FT-IR analysis was used to identify different photoactive functional groups that were responsible for the reduction of Fe (NO3)3 to IONPs. The crystalline nature of synthesized IONPs was revealed by XRD patterns with an average particle size ranging as 29 nm. The SEM image was employed to recognize the irregular morphology of synthesized nanoparticles. Moreover, significant antibacterial activity was observed at 1 mg/mL stock solution but after (125, 250, and 500 µg/mL) dilution, the synthesized IONPs showed moderate activity and became inactive at lower concentrations. The morphological and biochemical tests were used to confirm the presence of E. coli in the samples. Furthermore, the minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were carried out to determine the inhibitory concentrations for the isolated bacteria. The isolated E. coli were also subjected to antibiotic sensitivity testing that showed high resistance to antibiotics such as penicillin and amoxicillin. Thus, the findings of this study were to use IONPs against antibiotic resistance that has been developed in an inappropriate way.

16.
J Trop Med ; 2024: 6613120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784112

RESUMO

To determine the incidence of antimicrobial-resistant emerging pathogens, Clostridium difficile, and its associated risk factors in tertiary care setups of Pakistan. This cross-sectional prospective study was conducted from January 2019 to December 2020, to determine the prevalence and antimicrobial resistance patterns of C. difficile strains isolated from 450 stool specimens of patients suffering from diarrhea hospitalized in tertiary care hospitals in Peshawar, Pakistan. The stool samples of the patients were processed for culture and detection of toxin A and toxin B by enzyme-linked immunosorbent assay (ELISA) and tpi PCR. The drug sensitivity test was performed for antibiotics including ampicillin, cefixime, cefepime, amoxicillin, nalidixic acid, sulpha/TMP (SXT), chloramphenicol, metronidazole, vancomycin, ciprofloxacin, levofloxacin, and imipenem. Of 450 stool specimens, 108 (24%) were positive for C. difficile by stool culture, whereas 115 (25.5%) were only positive for C. difficile toxins based on ELISA and PCR (128 (28.6%). Of 108, 90.7% (n = 98) isolates were resistant to one antibiotic, and 90 (83.4%) were resistant to three or more antimicrobials. The highest resistance rates were found against penicillin (83.3%) followed by amoxicillin (70%), nalidixic acid (61%), and metronidazole (38%), and the lowest resistance was found against vancomycin (6.4%) and imipenem (3.7%). CDI was statistically significantly correlated with increased age, use of antibiotics, abdominal surgeries, use of proton pump inhibitors and H2a, and presence of comorbidities. The high frequency of C. difficile in Peshawar, Pakistan, indicates that CDI is an important nosocomial infection in different hospitals. The results will be helpful for clinicians to redesign control and therapeutic strategies in hospitals.

17.
Sci Rep ; 14(1): 14459, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914597

RESUMO

Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium associated with multiple nosocomial outbreaks. Antibiotic resistance increases healthcare costs, disease severity, and mortality. Multidrug-resistant infections (such as S. maltophilia infection) are difficult to treat with conventional antimicrobials. This study aimed to investigate the isolation rates, and resistance trends of S. maltophilia infections over the past 19 years, and provide future projections until 2030. In total, 4466 patients with S. maltophilia infection were identified. The adult and main surgical intensive care unit (ICU) had the highest numbers of patients (32.2%), followed by the cardiology department (29.8%), and the paediatric ICU (10%). The prevalence of S. maltophilia isolation increased from 7% [95% confidence interval (CI) 6.3-7.7%] in 2004-2007 to 15% [95% CI 10.7-19.9%] in 2020-2022. Most S. maltophilia isolates were resistant to ceftazidime (72.5%), levofloxacin (56%), and trimethoprim-sulfamethoxazole (14.05%), according to our study. A consistent and significant difference was found between S. maltophilia-positive ICU patients and non-ICU patients (P = 0.0017) during the three-year pandemic of COVID-19 (2019-2021). The prevalence of S. maltophilia isolates is expected to reach 15.08% [95% CI 12.58-17.59%] by 2030. Swift global action is needed to address this growing issue; healthcare authorities must set priorities and monitor infection escalations and treatment shortages.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/isolamento & purificação , Humanos , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Estudos Retrospectivos , Prevalência , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Masculino , Feminino , Adulto , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Farmacorresistência Bacteriana Múltipla , Unidades de Terapia Intensiva/estatística & dados numéricos , COVID-19/epidemiologia , Criança , Farmacorresistência Bacteriana , Idoso , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/tratamento farmacológico
18.
Healthcare (Basel) ; 11(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36766887

RESUMO

OBJECTIVES: E. cloacae is an opportunistic organism that causes serious infections, particularly in immuno-compromised and hospitalized patients, along with the emergence of resistance traits. The COVID-19 pandemic has impacted the epidemiological pattern and resistance traits of E. cloacae infections as well as those of other bacteria. The study aims to assess the epidemiological patterns, resistance characteristics and clinical outcomes of E. cloacae in Saudi Arabia and the impact of the COVID-19 pandemic. METHODS: King Fahad Medical City in Riyadh provided the data between January 2019 and December 2021 for the retrospective study of 638 isolates of E. cloacae. The clinical outcome of an E. cloacae infection was also determined by collecting and statistically analyzing the clinical records of 153 ICU patients. RESULTS: The total percentage of resistant E. cloacae isolates decreased from 48.36% in 2019 to 38% in 2020 and 37.6% in 2021. The overall mortality rate among ICU patients was 40.5%, with an adult age group having a substantial relative risk value of 1.37. CONCLUSION: E. cloacae is a prevalent nosocomial infection in which adult age is a significant risk factor for mortality. Moreover, this study emphasizes the importance of comparing E. cloacae resistance trends before and throughout the pandemic period in order to better understand the bacteria's behaviour.

19.
J Multidiscip Healthc ; 16: 1979-1988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484821

RESUMO

Introduction: Helicobacter pylori infection is widespread and harmful, rendering its eradication a serious public health problem. Undergraduate students' general understanding of H. pylori infection is relatively poor. This was a second-phase research study to evaluate the efficacy of an educational intervention in raising awareness among university students. Methods: A quasi-experimental approach was employed, with 108 undergraduate students at King Saud University as participants. First, during the October 2021 academic year, data were gathered using a validated survey. The survey was divided into sociodemographic characteristics and H. pylori knowledge. Second, we assessed the effectiveness of an educational intervention to increase university students' awareness of the topic. Results: Before the intervention, the percentage of students that had good (9.3%), fair (28.7%) and poor (62%) knowledge of H. pylori infection changed to 55.6%, 41.7%, and 2.8% respectively. There was a significant increase in overall and domain-wise mean knowledge score after the educational intervention (p = 0.001). The pretest knowledge was independent of all socio-demographic variables except "whether or not they had heard about H. pylori infection" (χ2= 8.666, p = 0.013). Conclusion: Educational intervention may help increase students' awareness of H. pylori infections.

20.
J Infect Public Health ; 16(3): 313-319, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36641839

RESUMO

BACKGROUND: Acinetobacter baumannii infection is a serious public health problem because it is highly resistant to antimicrobial therapy and causes a high fatality rate in critically ill patients. The aim of the study is to examine the demographics, microbiological findings, clinical presentation, and outcomes of multi-drug-resistant Acinetobacter baumannii respiratory infections in adult ICU intubated patients during COVID-19 pandemic. METHODS: This study included 115 mechanically ventilated adult ICU patients who had multi-drug-resistant Acinetobacter baumannii retrieved from respiratory samples during the COVID-19 pandemic in Albaha, Saudi Arabia. The information was obtained from medical and laboratory files. Univariate analysis was used to compare gender, COVID-19 infection, and outcomes. RESULTS: The rate of Acinetobacter baumanni respiratory infections among adult ICU patients was 6.2 %. Almost 93 % developed ventilator-associated pneumonia, and five of them developed bacteremia. The isolates had significant antibiotic resistance patterns, of which 3 % were pandrug-resistant bacteria. The death rate was 74 %, with major risk factors including sepsis, septic shock, VAP, liver diseases, and the use of inappropriate antibiotic therapy that lacked both colistin and tigecycline. Patients with COVID-19 coinfection had worse outcomes compared to non-COVID-19 patients. CONCLUSIONS: The identification of MDR-AB as a threat highlights the importance of surveillance studies in this region.


Assuntos
Acinetobacter baumannii , COVID-19 , Infecções Respiratórias , Adulto , Humanos , Estudos Retrospectivos , Estado Terminal , Pandemias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla
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