Evaluation of IL-8, nitric oxide and macrophage inhibitory factor as clinical circulatory markers in patients with cutaneous leishmaniasis, before and during sodium stibogluconate treatment.

The clinical spectrum of cutaneous leishmaniasis (CL), an intracellular parasitic pathogen, ranges from a single sore healing to chronic crusty lesions with a manifestation of treatment resistance. The complicated interaction between Leishmania bodies and the early immune response, including innate and adaptive mechanisms, determines the evolution of nodules. This study examined the levels of the chemoattractant interleukin 8 (IL-8), pro-inflammatory nitric oxide (NO), and immunoregulatory macrophage inhibitory factor (MIF) in the serum of subjects recently diagnosed with cutaneous leishmaniasis, in parallel with patients being monitored during consecutive sodium stibogluconate (Pentostam) treatment. A total of 161 serum samples of newly diagnosed individuals and patients undergoing pentostam injections were collected form an endemic area of Diyala, east central of Iraq. Sandwich ELISA was used to measure the level of IL-8, NO and MIF in the studied groups. Results of circulatory markers levels showed a considerable difference in all groups, with IL-8 being exceptionally higher in the first two groups of pretreated and dose-1 (191.5, 273.64) pg/ml respectively, while NO was found to be lower than in control subjects, particularly in the pretreated group (12.08 µmol/L) and MIF level was significantly higher in the pretreated group, which was (7.18 pg/ml). These findings can provide insights for distinction of disease phase and monitoring treatment efficacy along consecutive dosages, particularly in populations where CL is endemic.

Evaluation of in-service smartphone battery drainage profile for video calling feature in major apps.

Video calling is one of the most energy-intensive features in apps requiring the simultaneous operation of the mobile camera, display screen, audio speaker, and internet services. This feature impacts a smartphone battery's runtime and lifetime. This paper is the first of its kind experimental study, which quantifies the operating profile (discharge current, temperature, and terminal voltage) of video call feature in multiple widely used social media apps, which include WhatsApp, Facebook Messenger, Zoom, Skype, WeChat, Google Hangouts, Imo and Viber. One smartphone each of Vivo and Motorola has been evaluated as the manufacturer-provided application programming interface (API) allowed real-time measurement of the operating profile. Results indicate that the video calling feature for Facebook Messenger and Imo is the most energy efficient. In contrast, Google Hangouts is up to 35% more energy-intensive for video calling than other apps. Measurements also show that Vivo's in-service battery temperature is lower than Motorola due to its efficient chipset. For instance, during active Google Hangouts operation for 1 h, Vivo temperature is limited to 46 °C, whereas Motorola temperature rises to 52 °C. Finally, the influence of app algorithms and codecs on energy efficiency is also discussed with regard to operating performance.

Rectal Lymphoma: Report of a Rare Case.

Rectal lymphoma is a rare condition, presenting in less than 0.5% of all primary rectal neoplasms. Due to the disease's primary non-specific symptoms, its diagnosis is usually made at advanced stages. Clinically, it is indistinguishable from rectal carcinoma. The optimal approach for managing rectal lymphoma has still not been determined. We report a case of primary rectal diffuse large B-cell lymphoma (stage IV) in a 71-year-old Omani woman.

Detection of artemisinin effect on macrophage inducible nitric oxide gene expression in macrophage infected with Leishmania donovani.

Leishmaniosis is a parasitic infection spreads to humans by sand flies. Over 20 different species of Leishmania are responsible for the disease, which infect over 14 million people around the world. Chemotherapy is one of the most effective treatments for leishmaniosis, however it is restricted by the high cost and/or toxicity. In this study, the possible effect of artemisinin (ART) was detected on intracellular amastigotes of Iraqi strain of Leishmania donovani in ex vivo condition in U937 macrophage cell line. Gene expression of inducible nitric oxide synthase (iNOS) in U937 macrophage was investigated, before and after treatment with artemisinin. Kinetic result by real-time PCR demonstrated that the iNOS expression folding reached the maximum at concentration of 500 µM after 24 hours, at 750 µM after 48 hours and at 1000 µM after 72 hours, which was 56, 11, and 6, respectively. The copy number of iNOS gene expression was also significantly higher in treated infected U937 cells compared to both non-treated-infected cells and intact macrophages, under different concentration of ART along the three times of follow-up. Moreover, stained macrophages with fluorescent DAPI proved that the percentage of intracellular infective amastigotes was decreased to the minimum in treated U937 cells, in comparison to non-treated cells. The minimal amastigote-invasion percentage was recorded at 1000 µM, which was 26%, 27%, 21% compared to 61%, 87%, 75% in untreated cells after 24, 48, 72 hours respectively. These findings demonstrated ART positive efficacy against iNOS expression and this compound can be further studied as novel therapeutic rather than toxic available chemotherapies.

Extraction, Isolation and Nutritional Quality of Coffee Protein.

Coffee protein is reported to have high levels of branched-chain amino acids of value in sports nutrition and malnutrition recovery. However, data demonstrating this unusual amino acid composition are limited. We investigated the extraction and isolation of protein concentrates from coffee bean fractions, viz. green coffee, roasted coffee, spent coffee and silver skin, and determined their amino acid profile, caffeine content and protein nutritional quality, polyphenol content and antioxidant activity. Alkaline extraction/isoelectric precipitation gave lower concentrate yields and protein content than alkaline extraction/ultrafiltration. The protein concentrate from green coffee beans had a higher protein content than those from roasted coffee, spent coffee and silver skin, regardless of extraction method. The isoelectric precipitated green coffee protein concentrate had the highest in vitro protein digestibility and in vitro protein digestibility corrected amino acid score (PDCAAS). Silver skin protein concentrate had a very low digestibility and in vitro PDCAAS. In contrast to a previous finding, the amino acid levels in all coffee concentrates did not demonstrate high levels of branched-chain amino acids. All protein concentrates had very high levels of polyphenols and high antioxidant activity. The study suggested investigating coffee protein's techno-functional and sensory attributes to demonstrate their potential applications in different food matrices.

Hibiscus sabdariffa, a Treatment for Uncontrolled Hypertension. Pilot Comparative Intervention.

In Iraq, in 2019, there were about 1.4 million Internally Displaced Persons (IDP); medical treatments were often interrupted. The feasibility of using Hibiscus sabdariffa (HS) decoction to curb hypertension was evaluated. A multicentric comparative pilot intervention for 121 participants with high blood pressure (BP) (≥140/90 mmHg) was conducted. Participants of the intervention group (with or without conventional medication) received HS decoction on a dose regimen starting from 10 grams per day. BP was measured five times over six weeks. The major active substances were chemically quantified. Results: After 6 weeks, 61.8% of participants from the intervention group (n = 76) reached the target BP < 140/90 mmHg, compared to 6.7% in the control group (n = 45). In the intervention group, a mean (±SD) reduction of 23.1 (±11.8) mmHg and 12.0 (±11.2) for systolic and diastolic BP, respectively, was observed, while in the control group the reduction was 4.4 (±10.2)/3.6 (±8.7). The chemical analysis of the starting dose indicated a content of 36 mg of total anthocyanins and 2.13 g of hibiscus acid. The study shows the feasibility of using HS decoction in IDP's problematic framework, as hibiscus is a safe, local, affordable, and culturally accepted food product.

Artemisinin efficacy against old world Leishmania donovani: in vitro and ex vivo study.

Visceral leishmaniosis is one of the most fatal old-world neglected disease with estimated 90 thousand worldwide cases emerge each year. In Iraq, the cutaneous and visceral form are endemic but available chemotherapies are either toxic with diverse side effects, expensive available drugs or parasite resistant is arising. Artemisinin (ART) is a semi-synthetic compound which proved its effectiveness against protozoan parasites, such as malaria and Leishmania. In this study, the efficacy of different concentrations of pure artemisinin was screened in vitro against promastigotes and axenic amastigotes by MTT assay after 24, 48 and 27 hours follow up. In addition, the infectivity ability and number was investigated of intra-cellular Leishman bodies in treated murine peritoneal macrophages after 24 and 48 hours ART treatment. The results verified ART efficacy against the promastigotes and axenic amastigotes viability with IC50 measured after 24, 48- and 72-hours treatment. Infectivity percentage of murine macrophages and parasite burden were significantly reduced in treated cells. These findings indicate the leishmanicidal activity of ART against the Iraqi isolate of L. donovani and further in vivo study is recommended for assigning ART as a natural anti visceral leishmaniosis compound.

Curcumin Protects Against Radiotherapy-Induced Oxidative Injury to the Skin.

OBJECTIVE: Side-effects to normal tissues reduce the therapeutic window of radiotherapy. During radiotherapy, the skin is inevitably exposed to doses of ionizing radiation, leading to varying degrees of skin damage. Natural antioxidants have been explored for their radioprotective potentials. Thus, the present study aimed to investigate the protective effect of curcumin against radiotherapy-induced oxidative damage to the skin. METHODS: Forty rats were divided into four groups as follows: vehicle control (without irradiation or drug treatment), treatment with 150 mg/kg curcumin, 10 Gy single dose irradiation only, and 150 mg/kg curcumin plus 10 Gy radiation (RC). In the treatment groups, each rat was treated orally with 150 mg/kg curcumin 1 day before irradiation to 3 consecutive days after irradiation. Weeks 1, 2, or 4 after irradiation, all rats were sacrificed and their skin tissues collected and frozen at -80°C for the determination of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity in skin tissues. RESULTS: Radiotherapy-induced oxidative injury to the skin was evidenced by elevated MDA levels as well as depleted CAT, SOD, and GSH-Px activities. However, the administration of curcumin before and after irradiation prevented radiotherapy-induced oxidative damage by significantly elevating the activities of antioxidant enzymes. CONCLUSION: From the findings of the present study, curcumin showed potential for protection against radiotherapy-induced oxidative injury to the skin. However, future studies are required to evaluate its clinical efficacy.

Relationship between liver iron concentration determined by R2-MRI, serum ferritin, and liver enzymes in patients with thalassemia intermedia.

BACKGROUND: Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine aminotransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic resonance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. METHODS: In this cross-sectional study, 119 patients with TI (mean age years) were randomly selected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF and ALT levels, were assessed in all participants. A P-value <0.05 was considered statistically significant. RESULTS: SF and LIC levels were lower in patients with TI than in those with TM; only ferritin values were significant. We found a statistically significant relationship between SF and LIC, with cut-off estimates of SF in patients with TI who had splenectomy and those who entered puberty spontaneously (916 and 940 ng/mL, respectively) with LIC >5 mg Fe/g dry weight (P<0.0001). A significant relationship was also found for patients with TI who had elevated ALT level (63.5 U/L), of 3.15 times the upper normal laboratory limit, using a cut-off for LIC ≥5 mg Fe/g dry weight. CONCLUSION: We determined the cut-off values for ALT and SF indicating the best time to start iron chelation therapy in patients with TI, and found significant correlations among iron overload, SF, and ALT.

The Nutritional and Phytochemical Composition of the Indigenous Australian Pindan Walnut (Terminalia cunninghamii) Kernels.

Nutritional composition of the kernels of two types of Pindan walnut (Terminalia cunninghamii), a native nut consumed traditionally by Australian Indigenous peoples, is reported for the first time. Results showed that Pindan walnut kernels contained high levels of fat, protein and ash, approximately 50, 30 and 5% fresh basis, respectively. The levels of minerals in the kernels were much higher than common walnuts and macadamia nuts, especially those of phosphorus, magnesium and zinc. The high amounts of polyphenols in the kernels provided strong hydrophilic antioxidant capacities, of up to 2004 mg Trolox equivalents/100 g fresh basis using the hydrophilic oxygen radical absorbance capacity assay. Both free polyphenol content and hydrophilic antioxidant capacities of the kernels were higher than those of macadamia nuts, although the lipophilic oxygen radical absorbance capacity was lower. These preliminary studies indicate high potential for wider use of the Pindan walnut as a novel, nutritious and health-promoting food.

Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes.

Leishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphingolipid for synthesis of complex sphingolipid. In this study L. mexicana endocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis. Notably, in contrast to L. major, L. mexicana amastigotes are indicated to possess a complete biosynthetic pathway suggesting that scavenged sphingolipids may be nonessential for proliferation. This suggested that Old and New World species differ in their interactions with the macrophage host. This will need to be considered when targeting the Leishmania sphingolipid biosynthetic pathway with novel therapeutics.

Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa.

Given the paucity and toxicity of available drugs for leishmaniasis, coupled with the advent of drug resistance, the discovery of new therapies for this neglected tropical disease is recognised as being of the utmost urgency. As such antimicrobial peptides (AMPs) have been proposed as promising compounds against the causative Leishmania species, insect vector-borne protozoan parasites. Here the AMP temporins A, B and 1Sa have been synthesised and screened for activity against Leishmania mexicana insect stage promastigotes and mammalian stage amastigotes, a significant cause of human cutaneous disease. In contrast to previous studies with other species the activity of these AMPs against L. mexicana amastigotes was low. This suggests that amastigotes from different Leishmania species display varying susceptibility to peptides from the temporin family, perhaps indicating differences in their surface structure, the proposed target of these AMPs. In contrast, insect stage L. mexicana promastigotes were sensitive to two of the screened temporins which clearly demonstrates the importance of screening AMPs against both forms of the parasite.

Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain.

The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C(13)) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase.

Sphingolipids are key components of eukaryotic membranes, particularly the plasma membrane. The biosynthetic pathway for the formation of these lipid species is largely conserved. However, in contrast to mammals, which produce sphingomyelin, organisms such as the pathogenic fungi and protozoa synthesize inositol phosphorylceramide (IPC) as the primary phosphosphingolipid. The key step involves the reaction of ceramide and phosphatidylinositol catalysed by IPC synthase, an essential enzyme with no mammalian equivalent encoded by the AUR1 gene in yeast and recently identified functional orthologues in the pathogenic kinetoplastid protozoa. As such this enzyme represents a promising target for novel anti-fungal and anti-protozoal drugs. Given the paucity of effective treatments for kinetoplastid diseases such as leishmaniasis, there is a need to characterize the protozoan enzyme. To this end a fluorescent-based cell-free assay protocol in a 96-well plate format has been established for the Leishmania major IPC synthase. Using this system the kinetic parameters of the enzyme have been determined as obeying the double displacement model with apparent V(max)=2.31 pmol min(-1)U(-1). Furthermore, inhibitory substrate analogues have been identified. Importantly this assay is amenable to development for use in high-throughput screening applications for lead inhibitors and as such may prove to be a pivotal tool in drug discovery.

Calciphylaxis cutis: a case report and review of literature.

Calciphylaxis is a poorly understood syndrome of vascular calcification and skin necrosis. It affects 1-4% of the population with end stage renal disease (ESRD). Disorders implicated in the pathogenesis of calciphylaxis include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product, and secondary hyperparathyroidism (Essary, L.R. and Wick, M.R. (2000) Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. Am. J. Clin. Pathol. 113, 280-287, Beitz, J.M. (2004) Calciphylaxis:an uncommon but potentially deadly form of skin necrosis. Am. J. Nurs. 104, 36-37.). Although these abnormalities are extremely common in-patients with ESRD, calciphylaxis is relatively rare. The mortality rate of calciphylaxis is about 60-80%. The leading cause of death is sepsis from necrotic skin lesions (Hitti,W.A., Papadimitriou, J.C., Bartlett, S. and Wali, R.K. (2007) Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. Scand. J. Urol. Nephrol.1-3.). Here, we report a case of calciphylaxis in a 23-year-old female with past history of chronic renal failure, renal transplantation and intake of immunosuppressive drug. The relevant literature was discussed.