scholarly journals Efficacy of Artesunate + Sulphadoxine-Pyrimethamine (AS + SP) and Amodiaquine + Sulphadoxine-Pyrimethamine (AQ + SP) for UncomplicatedfalciparumMalaria in Equatorial Guinea (Central Africa)

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Pilar Charle ◽  
Pedro Berzosa ◽  
Miguel Angel Descalzo ◽  
Aida de Lucio ◽  
Jose Raso ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Age Groups ◽  
Central Africa ◽  
Equatorial Guinea ◽  
Pcr Analysis ◽  
Whatman Filter Paper ◽  
Combination Drugs ◽  
Late Treatment ◽  
Sulphadoxine Pyrimethamine

Objectives. The objectives of the study were (i) to evaluate the efficacy of combination drugs, such as artesunate + sulphadoxine-pyrimethamine (AS + SP) and amodiaquine + sulphadoxine-pyripethamine (AQ + SP) in treatment of uncomplicatedfalciparummalaria (ii) to differentiate recrudescence from reinfection by analysingmsp-1andmsp-2genes ofPlasmodium falciparumin treatment failure cases.Methods. We carried out an in vivo study in the year 2005 in 206 children between 6 to 59 months age groups. Of the 206, 120 received AQ + SP, and 86 received AS + SP. A clinical and parasitological followup during 14 days was undertaken. Finger-prick blood sample from each patient was taken on Whatman filter paper (no. 3) on days 0, 7, 14 and also the day when the parasite and symptoms reappeared for PCR analysis.Results. Late treatment failure was observed in 3.5% (4/114) with AQ + SP, and 2.5% (2/79) with AS + SP. The success rate was 96.5% with AQ + SP and 97.5% with AS + SP. No deaths and severe reactions were recorded. Out of the 6 treatment failure cases, one was reinfection as observed by PCR analysis ofmsp-1 andmsp-2 genes on day 14.Discussion. Both the combinations found to be efficacious and safe and could be used as a first-line treatment for uncomplicatedfalciparummalaria in Equatorial Guinea.

scholarly journals Efficacy and Tolerability of Malartin and Sulphadoxine-Pyrimethamine Combination against Uncomplicated Falciparum Malaria in Dibanda, Southwest Cameroon

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Helen Kuokuo Kimbi ◽  
Mesame Ntoko ◽  
Nelson N. Ntonifor ◽  
Emmaculate Lum ◽  
Anna L. Njunda ◽  
...  
Keyword(s):  
Falciparum Malaria ◽  
Drug Combination ◽  
Age Groups ◽  
Social Classes ◽  
Uncomplicated Falciparum Malaria ◽  
Artemisinin Derivatives ◽  
The Difference ◽  
Sulphadoxine Pyrimethamine

Artemisinin derivatives are now the most potent and rapidly acting antimalarials. The aim of this study was to assess thein vivoefficacy and tolerability of a combination of Malartin (an artesunate) and sulphadoxine-pyrimethamine (SP) in the treatment of uncomplicated falciparum malaria in Dibanda, Cameroon. A total of 197 subjects were recruited into the study and administered Malartin for 3 days and SP as a single dose on day 0. Only 174 of the subjects were successfully followed up on days 3, 7, and 14. The overall success rate of the drug combination was 92.53%. Parasite density decreased during the follow-up period in different age groups, sexes, and social classes. The prevalence of anaemia decreased from 22.99% at enrolment to 9.77% on day 14, and the difference was significant (P<0.05) on all days of followup. The drug combination did not give rise to any serious side effects.

scholarly journals Pfcrt mutant haplotypes may not correspond with chloroquine resistance

2014 ◽  
Vol 8 (06) ◽  
pp. 768-773 ◽  
Author(s):  
Diganta Goswami ◽  
Sunil Dhiman ◽  
Bipul Rabha ◽  
Dinesh Kumar ◽  
Indra Baruah ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Success ◽  
Chloroquine Resistance ◽  
Pfcrt Gene ◽  
Kaplan Meier ◽  
Chloroquine Treatment ◽  
Pcr Rflp ◽  
Pcr Products ◽  
Late Treatment

Introduction: Chloroquine resistance in Plasmodium falciparum is associated with mutations in pfcrt and pfmdr1 genes. The frequency distribution of pfcrt K76T and pfmdr1 N86Y mutations and their association with chloroquine susceptibility was studied in an endemic area along the Indo-Bangladesh border. Methodology: A single-arm prospective study of clinical and parasitological responses in P. falciparum malaria patients to chloroquine was conducted in vivo. PCR-RFLP assay was used to detect pfcrt K76T and pfmdr1 N86Y mutations in P. falciparum. The PCR products of pfcrt gene were sequenced,  translated and aligned for haplotyping. Results: Out of 63 cases, 44 (69.8%) responded adequately to chloroquine treatment. Pfcrt K76T mutation was recorded in 100% of the treatment failure cases, whereas pfmdr1 N86Y mutation was found in 52.6% of the cases only. Early treatment failure (84.2%) occurred more frequently than late treatment failure (15.8%). Kaplan–Meier survival analysis showed that the probability estimate for treatment success after 7 and 15 days was 0.84 (95% CI = 0.72-0.92) and 0.70 (95% CI = 0.57-0.80), respectively. Sequence analysis of 72 to 76 pfcrt gene codons revealed the presence of two mutant (CVMNT, CVIET) and two wild (CVMNK, CVIEK) haplotypes. The mutant CVIET haplotype was predominantly distributed (42.1%). Conclusions: The presence of mutations in pfcrt K76T and pfmdr1 N86Y genes is not sufficient to explain the therapeutic efficacy of chloroquine to P. falciparum. Study suggests that pfcrt K76T mutant haplotypes are widely distributed and are spreading diligently, which needs to be taken into account in devising an antimalarial policy.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

scholarly journals MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1202-1212
Author(s):  
Aichun Zhang ◽  
Yangzi Jin
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Pathway Activation ◽  
Nasal Lavage Fluid

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.

scholarly journals Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Vicente Urbano Nsue Ndong Nchama ◽  
Ali Hamad Said ◽  
Ali Mtoro ◽  
Gertrudis Owono Bidjimi ◽  
Marta Alene Owono ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Control ◽  
Malaria Infection ◽  
Age Groups ◽  
Control Measures ◽  
Equatorial Guinea ◽  
Safety And Efficacy ◽  
Bioko Island ◽  
Malaria Vaccines

Abstract Background Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. Methods A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. Results There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6–59-month-olds, 0.26 in 5–17-year-olds, 0.20 in 18–45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6–59-month-olds, 0.10 in 5–17-year-olds, 0.11 in 18–45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. Conclusion Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.

scholarly journals Three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomoyo Y. Irie ◽  
Tohru Irie ◽  
Alejandro A. Espinoza Orías ◽  
Kazuyuki Segami ◽  
Norimasa Iwasaki ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Age Groups ◽  
Three Dimensional ◽  
Hounsfield Unit ◽  
Lateral Wall ◽  
Ct Attenuation ◽  
Dimensional Distribution ◽  
The Mean ◽  
Pedicle Wall

AbstractThis study investigated in vivo the three-dimensional distribution of CT attenuation in the lumbar spine pedicle wall measured in Hounsfield Unit (HU). Seventy-five volunteers underwent clinical lumbar spine CT scans. Data was analyzed with custom-written software to determine the regional variation in pedicle wall attenuation values. A cylindrical coordinate system oriented along the pedicle’s long axis was used to calculate the pedicular wall attenuation distribution three-dimensionally and the highest attenuation value was identified. The pedicular cross-section was divided into four quadrants: lateral, medial, cranial, and caudal. The mean HU value for each quadrant was calculated for all lumbar spine levels (L1–5). The pedicle wall attenuation was analyzed by gender, age, spinal levels and anatomical quadrant. The mean HU values of the pedicle wall at L1 and L5 were significantly lower than the values between L2–4 in both genders and in both age groups. Furthermore, the medial quadrant showed higher HU values than the lateral quadrant at all levels and the caudal quadrant showed higher HU values at L1–3 and lower HU values at L4–5 than the cranial quadrant. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral wall.

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint

Cartilage ◽  
2020 ◽  
pp. 194760352098015
Author(s):  
Mara H. O’Brien ◽  
Eliane H. Dutra ◽  
Shivam Mehta ◽  
Po-Jung Chen ◽  
Sumit Yadav
Keyword(s):  
Age Groups ◽  
Mandibular Condyle ◽  
Bone Morphogenetic Protein 2 ◽  
Matrix Synthesis ◽  
Cartilage Growth ◽  
Chondrocyte Proliferation ◽  
Conditional Deletion ◽  
Morphogenetic Protein

Objective Bone morphogenetic protein 2 (BMP2) plays important roles in cartilage growth and development. Paradoxically, elevated levels of BMP2 leads to hypertrophic differentiation and osteoarthritis of cartilage. We examined the in vivo loss of BMP2 in cells expressing aggrecan of the mandibular condyle and knee. Design Three-week-old BMP2 flox/flox- CreER-positive mice and their Cre-negative littermates were treated with tamoxifen and raised until 3 or 6 months. We also investigated the direct effects of BMP2 on chondrocytes in vitro. Cells from the mandibular condyle of mice were treated with recombinant human BMP2 (rhBMP2) or rhNoggin (inhibitor of BMP2 signaling). Results Conditional deletion of BMP2 caused breakage of the cartilage integrity in the mandibular condyle of mice from both age groups, accompanied by a decrease in cartilage thickness, matrix synthesis, mineralization, chondrocyte proliferation, and increased expression of degeneration markers, while the effects at articular cartilage were not significant. In vitro results revealed that rhBMP2 increased chondrocyte proliferation, mineralization, and differentiation, while noggin induced opposite effects. Conclusions In conclusion, BMP2 is essential for postnatal maintenance of the osteochondral tissues of the mandibular condyle.

scholarly journals Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase

2021 ◽  
Author(s):  
Marco Fiorillo ◽  
Cristian Scatena ◽  
Antonio Giuseppe Naccarato ◽  
Federica Sotgia ◽  
Michael P. Lisanti
Keyword(s):  
Cell Migration ◽  
Treatment Failure ◽  
Atp Synthase ◽  
Atp Depletion ◽  
Multi Drug Resistance ◽  
Gamma Subunit ◽  
Primary Tumors ◽  
Atp Production ◽  
Mitochondrial Atp Synthase

AbstractHere, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important implications for understanding treatment failure and cancer cell dormancy. Using bioinformatic analysis of patient samples, we defined a mitochondrial-related gene signature for metastasis, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). The relationship between ATP5F1C protein expression and metastasis was indeed confirmed by immunohistochemistry. Next, we used MDA-MB-231 cells as a model system to functionally validate these findings. Importantly, ATP-high MDA-MB-231 cells showed a nearly fivefold increase in metastatic capacity in vivo. Consistent with these observations, ATP-high cells overexpressed (i) components of mitochondrial complexes I–V, including ATP5F1C, and (ii) markers associated with circulating tumor cells (CTCs) and metastasis, such as EpCAM and VCAM1. Knockdown of ATP5F1C expression significantly reduced ATP-production, anchorage-independent growth, and cell migration, as predicted. Similarly, therapeutic administration of the FDA-approved drug, Bedaquiline, downregulated ATP5F1C expression in vitro and prevented spontaneous metastasis in vivo. In contrast, Bedaquiline had no effect on the growth of non-tumorigenic mammary epithelial cells (MCF10A) or primary tumors in vivo. Taken together, our results suggest that mitochondrial ATP depletion is a new therapeutic strategy for metastasis prophylaxis, to avoid treatment failure. In summary, we conclude that mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression.

scholarly journals Targeting a Lipid Desaturation Enzyme, SCD1, Selectively Eliminates Colon Cancer Stem Cells through the Suppression of Wnt and NOTCH Signaling

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 106
Author(s):  
Yeongji Yu ◽  
Hyejin Kim ◽  
SeokGyeong Choi ◽  
JinSuh Yu ◽  
Joo Yeon Lee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Notch Signaling ◽  
Cultured Cells ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Dependent Manner ◽  
Lipid Desaturation ◽  
Novel Target

The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.

scholarly journals Programmed cell death 4 (PDCD4) expression during multistep Barrett's carcinogenesis

2010 ◽  
Vol 63 (8) ◽  
pp. 692-696 ◽  
Author(s):  
Matteo Fassan ◽  
Marco Pizzi ◽  
Giorgio Battaglia ◽  
Luciano Giacomelli ◽  
Paola Parente ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Intestinal Metaplasia ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Low Grade ◽  
Cytoplasmic Staining ◽  
Programmed Cell Death 4 ◽  
Columnar Metaplasia

AimTo test the contribution of programmed cell death 4 (PDCD4) tumour suppressor gene in Barrett's carcinogenesis.MethodsPDCD4 immunohistochemical expression was assessed in 88 biopsy samples obtained from histologically proven long-segment Barrett's mucosa (BM; 25 non-intestinal columnar metaplasia, 25 intestinal metaplasia (IM), 16 low-grade intraepithelial neoplasia (LG-IEN), 12 high-grade IEN (HG-IEN) and 10 Barrett's adenocarcinoma (BAc)). As controls, 25 additional samples of native oesophageal mucosa (N) were obtained from patients with dyspepsia. To further support the data, the expression levels of miR-21, an important PDCD4 expression regulator, in 14 N, 5 HG-IEN and 11 BAc samples were determined by quantitative real-time PCR analysis.ResultsPDCD4 immunostaining decreased progressively and significantly with the progression of the phenotypic changes occurring during Barrett's carcinogenesis (p<0.001). Normal basal squamous epithelial layers featured strong PDCD4 nuclear immunoreaction (mostly coexisting with weak–moderate cytoplasmic staining). Non-intestinal columnar metaplasia and intestinal metaplasia preserved a strong nuclear immunostaining; conversely, a significant decrease in PDCD4 nuclear expression was seen in dysplastic (LG-IEN and HG-IEN) and neoplastic lesions. Weak–moderate cytoplasmic immunostaining was evident in cases of LG-IEN, while HG-IEN and BAc samples showed weak cytoplasmic or no protein expression. As expected, miR-21 expression was significantly upregulated in HG-IEN and BAc samples, consistently with PDCD4 dysregulation.ConclusionsThese data support a significant role for PDCD4 downregulation in the progression of BM to BAc, and confirm miR-21 as a negative regulator of PDCD4 in vivo. Further efforts are needed to validate PDCD4 as a potential prognostic marker in patients with Barrett's oesophagus.

Sign in / Sign up

Export Citation Format

Share Document