Cells Mm-3 Research Articles

SARS-CoV-2 mRNA Vaccine Response in People Living with HIV According to CD4 Count and CD4/CD8 Ratio.

Our aim was to estimate the rates of not achieving a robust/above-average humoral response to the COVID-19 mRNA vaccine in people living with HIV (PLWH) who received ≥2 doses and to investigate the role of the CD4 and CD4/CD8 ratio in predicting the humoral response. We evaluated the humoral anti-SARS-CoV-2 response 1-month after the second and third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/above-average response using two criteria: (i) a humoral threshold identified as a correlate of protection against SARS-CoV-2 (<90% vaccine efficacy): anti-RBD < 775 BAU/mL or anti-S < 298 BAU/mL, (ii) threshold of binding antibodies equivalent to average neutralization activity from the levels of binding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratified according to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to compare the probability of not achieving robust/above-average responses. A mixed linear model was used to estimate the mean anti-RBD titer at various time points across the exposure groups. a total of 1176 PLWH were included. The proportions of participants failing to achieve a robust/above-average response were significantly higher in participants with a lower CD4 and CD4/CD8 ratio, specifically, a clearer gradient was observed for the CD4 count. The CD4 count was a better predictor of the humoral response of the primary cycle than ratio. The third dose was pivotal in achieving a robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm3 and a ratio > 0.6. A robust humoral response after a booster dose has not been reached by 50% of PLWH with CD4 < 200 cells mm3. In the absence of a validated correlate of protections in the Omicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.

EFEKTIVITAS WADAH BUNDAR BERARUS TERHADAP PENINGKATAN RESPON IMUN BENIH IKAN MAS (Cyprinus carpio) YANG DIINFEKSI OLEH BAKTERI Aeromonas hydrophila

This research focused on determining the best survival performance of carp (C. carpio) fingerlings in circular containers combined with venturi aerators to generate water current, then challenged by A. hydrophila. The research used an experimental method of Completely Randomized Design (CRD) with four treatments and four replications. The treatment used was the use of venturi aerators on circular containers: without water current as a control (A), with a water current of 0.06 ms?¹ (B), 0.1 ms?¹ (C), and 0.14 ms?¹ (D). The study was initiated by rearing 5-7 cm fish fingerlings for 40 days and followed by a challenge test for 14 days. Carp fingerlings were challenged by A. hydrophila intraperitoneally at a density of 10? CFU ml?¹. Each tank consists of 15 fingerlings. Parameters observed included survival rate, the number of red blood cells and white blood cells, macroscopic symptoms, and water quality. The results showed survival rate in treatment (D) was the best (water current of 0.14 ms?¹), 98% before the challenge period and 95% after the challenge period. In addition, it can increase the hematological parameters as seen from the increase in the number of red and white blood cells after the challenge test, from 1.043 x 106 cells mm³?¹ to 2.36 x 106 cells mm³?¹ and 2.7 x 104 cells mm³?¹ to 9.3 x 104 cells mm³?¹ respectively. And it shows an increased immune response as seen from the recovery acceleration in macroscopic symptoms on the seventh day after A. hydrophila injection. While water quality did not differ between control and treatments.Keywords : current circular generating tank, carp fingerling, Aeromonas hydrophila, immune response

The Body Fat Percentage Rather Than the BMI Is Associated with the CD4 Count among HIV Positive Japanese Individuals.

Maintenance of the cluster of differentiation 4 (CD4) positive lymphocyte count (CD4 count) is important for human immunodeficiency virus (HIV) positive individuals. Although a higher body mass index (BMI) is shown to be associated with a higher CD4 count, BMI itself does not reflect body composition. Therefore, we examined the association of body weight, body composition and the CD4 count, and determined the optimal ranges of CD4 count associated factors in Japanese HIV positive individuals. This cross-sectional study included 338 male patients treated with antiretroviral therapy for ≥12 months. Multiple logistic regression analysis was used to identify factors significantly associated with a CD4 count of ≥500 cells (mm3)−1. The cutoff values of factors for a CD4 ≥ 500 cells (mm3)−1 and cardiovascular disease risk were obtained by receiver operating characteristic curves. Age, body fat percentage (BF%), nadir CD4 count, duration of antiretroviral therapy (ART), years since the HIV-positive diagnosis and cholesterol intake showed significant associations with the CD4 count. The cutoff value of BF% for a CD4 ≥ 500 cells (mm3)−1 and lower cardiovascular disease risk were ≥25.1% and ≤25.5%, respectively. The BF%, but not the BMI, was associated with CD4 count. For the management of HIV positive individuals, 25% appears to be the optimal BF% when considering the balance between CD4 count management and cardiovascular disease risk.

A Case Report on Malaria

Introduction: Malaria is caused by the parasitic protozoan Plasmodium. It is a vector-borne disease which is transmitted from person to person via bites from infected mosquitoes. Following a mosquito bite the parasites multiply in the liver and subsequently infect red blood cells. It is a mosquito-borne illness. Fever or flu symptoms include shivering chills, headaches, and muscle pains. Anemia, jaundice, nausea, and diarrhea are some of the symptoms of malaria.&#x0D; Main Symptoms and Important Clinical Findings: A 24-year-old woman was admitted in. Acharya vinoba bhave rural hospital with chief complaint of stomach pain as her primary complaint. Then after several days Fever, pain, fatigue, headache occur. Several diagnostic evaluations done which shows total Red blood cells count: 4.8 million cu mm; white cell count: 11.810 cells mm3; lymphocytes: 11.2% platelets drop on smear, RBCs are moderated.&#x0D; The Main Diagnoses, Therapeutic Interventions, and Outcomes: 24 years old women admitted in Acharya vinoba bhave rural hospital with the chief complaint of stomach pain, fever, fatigue, headache and after all investigation she has diagnosed as malaria. Doctor manage with Iv fluids, cap. Doxycycline 100 mg, tab.dolo 650 mg, tab.larigo 650 mg, emset 4 mg injection Once a day, she was also given the Calcium Tab. Her condition has improved as a result of the treatment. The fever and agony had subsided.&#x0D; Conclusion: My patient was admitted to Acharya vinoba bhave rural hospital with a known case of malaria and a fever and discomfort complaint. Her condition improved after she received proper therapy.

Viability of Osteochilus Hasselti Padjadjaran Strain Against Aeromonas Hydrophila Infection

The purpose of this research is to reveal the viability of the new strain : nilem carp padjadjaran strain that challenged by Aeromonas hydrophila. The treatments are common carp (Cyprinus carpio), nilem carp (Osteochilus hasselti) and nilem carp (O. hasselti) padjadjaran strain that intraperitoneally challenged by A. hydrophila with 108 cfu ml-1. Parameters observed are mortality hours, gross pathological symptoms and haematological profile for 24 hour. Nilem padjadjaran strain mortality reached 100% after 10th hour postchallenge, while common carp and nilem reached 100% mortality in 14th hour postchallenge. Gross pathological symptoms showed reddish lesions, abdominal dropsy and exopthalmia, with first sign of reddish lesions is appeared in nilem padjadjaran strain at 3rd hour postchallenge. Feed responses of all fish are lost in 7th hour postchallenge. Nilem padjadjaran strain has no shock responses in 9th hour postchallenge. Total erythrocyte counts of common carp, nilem and nilem padjadjaran strain before challenged are 2,15 x 106, 2,45 x 106 dan 2,14 x 106 cells mm3-1, after 10th hour postchallenge becomes 1,2 x 106, 1,69 x 106 dan 1,21 x 106 cells mm3 -1. Total leukocyte count of common carp, nilem and nilem padjadjaran strain before challenged are 6,48 x 104, 7,36 x 104 and 6,56 x 104 cells mm3-1, and tend to increase in 3rd and 7th hour postchallenge (8,8 x 104, 9,12 x 104 dan 105 cells mm3-1 and 1,26 x 105, 1,3 x 105, 1,27 x 105 cells mm3-1), but in 10th hour postchallenge the total leukocyte count becomes decreased again (1,24 x 105, 1,26 x 105, 1,18 x 105 cells mm3 -1). Thus, nilem carp padjadjaran strain has no better immune performance than its parents.

Febrile Syndrome in HIV positive patients

Fever is one of the accompanying symptoms of HIV, mainly in the advanced stages of the disease, but its occurrence is related to a number of factors such as CD4+ Lymphocyte level, accompanying opportunistic infections; causative microorganisms etc. Fever accompanies HIV from the initial stage of the “acute retroviral syndrome” infection and during the evolution of the pathology towards the AIDS stage, even in IRIS. Fever-related opportunistic infections are divided into two groups by infectious or non-infectious causes3,4. In our study, we included 355 HIV-positive cases who had febrile episodes in different stages of immunodeficiency. In the HIV stage (to which we referred lymphocytes CD4+ over 500 cells/mm3, and without AIDS-related opportunistic infections) there were 39 cases. In the AIDS stage, there were 143 cases with a CD4 + level of 200-400 cells/mm3: pulmonary manifestations 85 cases, gastrointestinal 58 cases. With a level of CD4+ lymphocytes below 200 cells/ mm3 123 cases; pulmonary involvement 45 cases, intestinal 32 cases, CNS 11 cases, hematological.13 cases, disseminated 15 cases, FUO 7 cases. With CD4+ level below 50 cells mm3, 50 cases: non-Hodgkin’s lymphoma 9 cases. MAC 3 cases, TBC.19 cases, CNS lymphoma. 6 cases, retinal CMV 3 cases, Kaposi’s sarcoma 10 cases.

Nectar yeasts enhance the interaction between Clematis akebioides and its bumblebee pollinator.

It has been hypothesised that intense metabolism of nectar-inhabiting yeasts (NIY) may change nectar chemistry, including volatile profile, which may affect pollinator foraging behaviours and consequently plant fitness. However, empirical evidence for the plant-microbe-pollinator interactions remains little known. To test this hypothesis, we use a bumblebee-pollinated vine Clematis akebioides endemic to southwest China as an experimental model plant. To quantify the incidence and density of Metschnikowia reukaufii, a cosmopolitan NIY in floral nectar, a combination of yeast cultivation and microscopic cell-counting method was used. To examine the effects of NIY on plant-pollinator interactions, we used real flowers filled with artificial nectar with or without yeast cells. Then the volatile metabolites produced in the yeast-inoculated nectar were analysed with coupled gas chromatography and mass spectrometry (GC-MS). On average 79.3% of the C.akebioides flowers harboured M.reukaufii, and cell density of NIY was high to 7.4×104 cells mm-3 . In the field population, the presence of NIY in flowers of C.akebioides increased bumblebee (Bombus friseanus) pollinator visitation rate and consequently seed set per flower. A variety of fatty acid derivatives produced by M.reukaufii may be responsible for the above beneficial interactions. The volatiles produced by the metabolism of M.reukaufii may serve as an honest signal to attract bumblebee pollinators and indirectly promote the female reproductive fitness of C.akebioides, forming a potentially tripartite plant-microbe-pollinator mutualism.

Prioritization of antiretroviral therapy in patients with high CD4 counts, and retention in care: lessons from the START and Temprano trials.

Initiation of antiretroviral therapy is not a once in a lifetime opportunity. In some resource constrained settings financial limitations make it necessary to prioritize treatment initiation for some groups of patients. In developed countries, there are patients who are reluctant to initiate treatment. Subgroup analysis of the START trial can inform recommendations for which patients with CD4 counts >500 cells mm3 temporary postponement of treatment initiation is safer. These include individuals aged <30 years and/or with CD4/CD8 ratio of >0.8 and/or viral load of <5000. This is because these individuals are at very low risk of disease progression in the subsequent 2 to 3 years, the risk is minimally diminished by antiretroviral therapy and is virtually identical in the first 18 months of therapy regardless of treatment initiation. In addition, asymptomatic young individuals are at higher risk of loss‐to‐follow and of low adherence to treatment, and those with low viral loads are less likely to transmit the virus. In addition, lessons from START and Temprano can help design trials to investigate strategies to decrease losses‐to‐follow‐up, while minimizing risks to patients.

Hematologic abnormalities and associated factors among HIV infected children pre- and post-antiretroviral treatment, North West Ethiopia.

IntroductionThere are few studies on the hematologic parameters of HIV-infected individuals in Ethiopia; of these, almost all studies researched adults. Our current study is unique in that it mainly focused on the pediatric population and compared both pre- and post-antiretroviral therapy (ART) children. Inference from this study can be used for other developing countries where the burden of HIV disease is high.ObjectiveThe aim of this study was to identify hematologic abnormalities in HIV-infected children before and after initiation of ART.MethodologyA cross-sectional study was conducted on HIV-infected children from June 1 to August 30, 2015. Data were collected using a pretested and structured questionnaire. Statistical analysis was performed using SPSS 20 version.ResultsThe median age of study subjects was 10 years with an interquartile range (IQR) of (6, 12). Two-thirds (74.3%) of study subjects received ART for >1 year. The median of CD4 count before ART was 490 cells/mm3 with an IQR of (286, 765); this increased to 663 cells mm3 with an IQR of (499, 908) after ART. Likewise, the median of hemoglobin before ART was 11.5 mg/dL with an IQR of (9.9, 13), which increased after ART to 13 mg/dL with an IQR of (11.8, 14). The prevalence of anemia was 42.8% before and 18.9% after ART initiation. The median of absolute neutrophil count before ART was 3×103 with an IQR of (2.1, 4.6) and after ART, it became 3×103 with IQR of (1.9, 4.2). Age <5 years (adjusted odds ratio [AOR]: 2.76; 95% CI: 1.5, 5.0), an advanced stage of AIDS (AOR: 2.8; 95% CI: 1.4, 5.6) and CD4% <25% (AOR: 2.4; 95% CI: 1.2, 4.9) were significantly associated with anemia before ART initiation, while opportunistic infections were associated with anemia after initiation of ART (AOR: 2.3; 95% CI: 1.08, 4.8).ConclusionART positively or negatively affects the hematologic profile of HIV-infected children. The current study demonstrated a significant reduction of anemia after initiation of ART.

Effects of Nicotine and Sodium Bicarbonate on Blood Parameters of Albino Rats (&amp;lt;i&amp;gt;Rattus norvegicus&amp;lt;/i&amp;gt;)

In this study, the effects of nicotine and sodium bicarbonate on some blood parameters of male albino rats were investigated. Seventy five albino rats of 90 days old and average body weight of 190g were used. These animals were randomly selected into five groups, A, B, C, D, and E of five rats each. This experiment was replicated three times. Group A was the control group and they were given normal saline. Group B was treated with only nicotine of 0.5ml of 1g/100ml while other groups, C, D, and E received this same concentration of nicotine but with varying concentration levels of (1ml, 2ml, and 3ml of 2g/100ml) of sodium bicarbonate respectively. The treatments were administered orally using gastrointestinal cannular for four weeks. The result showed elevations of serum level in aspartate aminotransferase (AST), alanin aminotransferase (ALT) and alkaline phosphatase (ALP) in the entire treated groups but there was no significant difference, when compared with the control. There was significant difference (P < 0.05) in WBC of group B when compared with the control group, and the value obtained from group A was 10.6 x 103 ± 333 cells mm-3, while 4.4 x 103 ± 333 cells mm-3 was obtained from group B. There was also significant difference in RBC value of group B, ( P < 0.05) when compared with the control group, and the value obtained from group A, the control group was 10.6x106±620 cells mm-3 while 4.6 x106 ± 340 cells mm-3 was obtained from group B. Also, there was significant difference in PCV mean values of group B, C, and D, (P < 0.05) when compared with the control group. The value obtained from group A, the control group was 42 ± 0.5 % while 27.3 ± 1.7 %, 35 ± 1.5 %, and 36 ± 2.3 % were obtained from group B, C, and D respectively. Generally, effects of nicotine were much in group B that received 0.5ml of nicotine without sodium bicarbonate, and these effects decreased as concentration of sodium bicarbonate increased in other groups with fixed concentration of nicotine.

Involvement of the Genetic Diversity of HIV-1 in the Virological Treatment Failure of First Line Antiretroviral in Kinshasa

Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to determine the rate of virological treatment failure and the involvement of genetic diversity and different mutations in this failure in Kinshasa. Methods: Of the 153 Antiretroviral-naive patients who were included in the cohort, 138 patients have been received for the appointment of the 6th month. Clinical parameters were recorded on individual patient charts. The determination of Viral Load (VL) was done at the Laboratory of Molecular Biology. Clinical and biological parameters of the 6th month were compared with those taken at baseline of the cohort to determine the evolution of patients under treatment. Results: At the consultation of the 6th month, 138 patients (90.2%) had returned out of the 153 included. Eighty-one (58.7%) patients were women and 57 (41.3%) men. The age of patients is between 18 and 65 with an average of 37 years. Ten deaths (6.5%) and 5 (3.3%) lost have been reported. One hundred twenty-five patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4. The median CD4 T cells is 560 cells mm3. The median VLs of patients was 0.90 log10 RNA copies/ml. Of the 34 patients in virological failure, 8 (23.5%) are minimal failure, 23 (67.7%) in moderate failure and 3 (8.8%) in severe failure. According to the Pearson’s test, VLs at 6th months were highly correlated with that of inclusion, with V75 and K70 mutations for NRTIs, with V108 mutation for NNRTI well as the virological failure of treatment. Conclusion: Our results confirmed the hypothesis that high Viral Load at the start of the treatment is a poor prognosis for the development of therapy. Transmitted mutations are involved in treatment failure.

Stereological analysis of size and density of hepatocytes in the porcine liver.

The porcine liver is frequently used as a large animal model for verification of surgical techniques, as well as experimental therapies. Often, a histological evaluation is required that include measurements of the size, nuclearity or density of hepatocytes. Our aims were to assess the mean number-weighted volume of hepatocytes, the numerical density of hepatocytes, and the fraction of binuclear hepatocytes (BnHEP) in the porcine liver, and compare the distribution of these parameters among hepatic lobes and macroscopic regions of interest (ROIs) with different positions related to the liver vasculature. Using disector and nucleator as design-based stereological methods, the morphometry of hepatocytes was quantified in seven healthy piglets. The samples were obtained from all six hepatic lobes and three ROIs (peripheral, paracaval and paraportal) within each lobe. Histological sections (thickness 16μm) of formalin-fixed paraffin-embedded material were stained with the periodic acid-Schiff reaction to indicate the cell outlines and were assessed in a series of 3-μm-thick optical sections. The mean number-weighted volume of mononuclear hepatocytes (MnHEP) in all samples was 3670±805μm3 (mean±SD). The mean number-weighted volume of BnHEP was 7050±2550μm3 . The fraction of BnHEP was 4±2%. The numerical density of all hepatocytes was 146997±15738 cellsmm-3 of liver parenchyma. The porcine hepatic lobes contained hepatocytes of a comparable size, nuclearity and density. No significant differences were identified between the lobes. The peripheral ROIs of the hepatic lobes contained the largest MnHEP with the smallest numerical density. The distribution of a larger MnHEP was correlated with a larger volume of BnHEP and a smaller numerical density of all hepatocytes. Practical recommendations for designing studies that involve stereological evaluations of the size, nuclearity and density of hepatocytes in porcine liver are provided.

Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons.

Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210–429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7–4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02–0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01–4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.

The effect of two orchard light management practices on the sensory quality of apple: fruit thinning by shading or photo-selective nets

SummaryThe effects of innovative techniques for orchard light management on the sensory properties and quality of apple (Malus _ domestica Borkh.) fruit were measured using sensory and instrumental techniques. In the first experiment, ‘Rosy Glow’ fruit, thinned chemically or by shading, were compared. In the second experiment, ‘Fuji’ fruit were grown under five different coloured photo-selective hail nets and compared. For ‘Rosy Glow’ fruit, the efficacy of both thinning methods was comparable in terms of crop load, and no sensory differences were perceived between treatments by a trained sensory panel, based on quantitative descriptive profiling, except for the “green flesh” attribute. Nevertheless, ‘Rosy Glow’ fruit from the shade-based thinning had a higher mean fresh weight (FW; 215 g vs. 198 g) and higher titratable acidity (5.3 vs. 4.5 malic acid eq. 100 g-1 juice). Some significant differences were reported by the trained sensory panel for four out of the ten attributes rated among the ‘Fuji’ apples produced under the neutral black net (control), and the red, white, yellow, and blue photo-selective hail nets. Differences were greatest between fruit from the red and yellow hail nets. Apples from the red hail net had higher scores for yellow colour perception (average intensity 42.3 vs. 28.5, based on a linear scale anchored at 0 as the minimum and 100 as the maximum), sweet taste (score 54.9 vs. 42.4), and hardness (i.e., sensory definition for firmness; score 52.0 vs. 43.0), and a lower score for green colour (4.6 vs. 10.0). In terms of objective instrumental measurements, fruit from the red net treatment had a higher mean FW (217 g), with larger cells and larger intercellular spaces measured in terms of the number of cells mm-3 and the percentage of intercellular spaces, and a higher mean dry matter (DM) content [14.7% (w/w)], when compared to fruit from the other photo-selective net treatments. The spectrum of transmitted light influenced fruit growth by affecting cell proliferation and ripening, which changed the sensory perceptions of fruit appearance, taste, and texture.This study demonstrated that it is possible to use sensory panel analysis to measure the impact of new pre-harvest treatments on the quality of harvested apple fruit.

Hematologia e tempo de migração de mácrofagos em surubim Pseudoplatystoma spp. frente a inoculação de Saccharomyces cerevisae

It was studied in this work the definition of time in phagocytic activity of macrophages in the celomatic cavity in surubim Pseudoplatystoma spp. and the hematological and biochemistry alterations after the inoculation of Saccharomyces cerevisae. 24 fishes weighting an average of 15,6 ± 4,3 g were used. The delineation used was entirely randomized, and the incubation times were one, two and three hours, and a control group, where six fishes were used per group. For inoculation, 1.5 mL of solution of yeast Saccharomyces cerevisiae in concentration of 9,000 cells mm-3 were injected intraperitoneally. The hematological and biochemistry variables analyzed were: hematocrit, hemoglobin, total number of erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin concentration, trombocyte count of total blood and total count of differential leukocyte and glucose. The phagocytic capacity and index of macrophages were evaluated. Variance analysis was performed (P<0.05) and the means that showed significative diffence were compared through the Tukey test at 5%. The eosinophills concentration was lower in the times of two and three hours compared to the control group. There was not significative difference to the plasmatic glucose among the times of incubation. The incubation period of two hours proved to be enough to promote migration and optimal activation of serubim macrophages.

P3.097 Socio-Demographic Characteristics and Drug Related High Risk Behaviour in People Who Inject Drugs (PWID) Recently Diagnosed HIV Positive in Barnaul, Russia

BackgroundIn 2012 60.4% of registered HIV cases were attributed to injection drug use in Russia and is up 8% in Barnaul (2012). We sought to describe socio-demographic and drug related...

Suppression of vascular endothelial growth factor expression by RNA interference in human skin squamous cell carcinoma xenografts in nude mouse models.

Objective To observe the effect of short hairpin RNA (shRNA)-mediated vascular endothelial growth factor (VEGF) gene silencing on the growth of human skin squamous cell carcinoma(SCC) xenografts in nude mice.Methods Two eukaryotic expression plasmids targeting VEGF gene,including psilencer-VEGF1-shRNA (VEGF-s1) and psilencer-VEGF2-shRNA (VEGF-s2),as well as one negative control plasmid containing random target sequence (psilencer-Target-off-shRNA,T-off),were chemically synthesized,and transfected into a human skin SCC cell line A431 to develop stably transfected cell lines.Real time quantitative PCR (RT-qPCR) and double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) were carried out to measure the expression of VEGF mRNA and protein respectively in A431 cells.Twelve nude mice were divided into 4 goups to be subcutaneously inoculated in the axillary region with untransfected A431 cells as well as A431 cells transfected with VEGF-s1,VEGF-s2 and T-off,respectively.The tumor growth was observed in nude mice every 5 days.Twenty days after the inoculation,the mice were sacrificed,and transplanted tumors were obtained from the mice and subjected to an immunohistochemical study for the measurement of VEGF,proliferating cell nuclear antigen (PCNA) and CD34 expression.Data were statistically analyzed by using the Stata 7.0 software,and t test was conducted to compare the differences between groups.Results The mRNA and protein expression levels of VEGF were significantly lower in A431 cells transfected with VEGF-s1 and VEGF-s2 than in untransfected A431 cells (27.85 ± 3.95 and 24.69 ± 2.83 vs.54.06 ± 6.38,t =6.05,7.29,both P＜ 0.01; 32.67 ± 2.52 and 29.27 ± 1.10 vs.52.85 ± 2.23,t =8.04 and 11.53,both P＜0.01 ).Twenty davs after the inoculation,the volume and weight of xenografted tumors in mice inoculated with VEGF-sl- and VEGF-s2-transfected A431 cells were significantly lower than those in mice with untransfected A431 cells ( ( 192.50 ± 10.90) mm3 and (203.67 ± 3.21 )mm3 vs.(272.00 ± 21.07) mm3,t =5.80 and 5.55,both P＜ 0.01; (0.05 ± 0.03) g and (0.13 ± 0.04) g vs.(0.25 ± 0.02) g,t =9.60 and 4.64,both P＜ 0.01 ).Decreased expression rate of VEGF,PCNA and number of CD34-positive vessels were observed in the xenografted tumor tissue from mice inoculated with VEGF-sl- and VEGF-s2-transfected A431 cells compared with that from mice with untransfected A431 cells (52.00％ ± 2.00％ and 56.67％ ± 3.06％ vs.70.00％ ± 2.00％,both P ＜ 0.01;37.01％ ± 2.41％ and 33.94％ ± 3.25％ vs.72.11％ ± 3.02％,both P＜ 0.01; 2.05 ± 0.07 and 1.72 ± 0.10 vs.4.01± 1.27,both P ＜ 0.01).No significant differences were observed in the above parameters between cells transfected with VEGF-s1- and VEGF-s2-transfected A431 cells,between untransfected and T-off-transfected A431 cells,between tumor xenografts derived from VEGF-sl- and VEGF-s2-transfected A431 cells,or between tumor xenografts derived from untransfected and T-off-transfected A431 cells (all P ＞ 0.05).Conclusions The shRNA targeting VEGF gene can significantly inhibit the expression of VEGF in A431 cells and A431-derived tumor xenografts in nude mice,in turn suppress the growth and attenuate the malignant phenotype of tumor. Key words: Carcinoma, squamous cell; Animal experimentation; Cell line, tumor; RNA interference; Vascular endothelial growth factors

Cefepime Monotherapy is as Effective as Ceftriaxone Plus Amikacin in Pediatric Patients with Cancer and High-Risk Febrile Neutropenia: A Randomized Comparison

The empirical use of antibiotic therapies is widely accepted in patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum antibiotics in patients with high-risk of complications is an appropriate alternative. However, few data are available in pediatric patients. We conducted a prospective, randomized, open study in patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients were randomized to receive cefepime (CFP) or ceftriaxone plus amikacin (CFT+AK). A total of 57 patients with 125 episodes of fever and neutropenia were evaluated (CFP, 62 and CFT + AK, 63 episodes). The mean neutrophil count at admission was 118.6 cells mm-3 (CFP) and 107 cells mm-3 (CFT+AK). The mean duration of neutropenia was 9.0 days (CFP) and 8.0 days (CFT+AK). Analyzing only the first episodes of each patient, CFP treatment was successful in 65.5% of the episodes and CFT+AK were successful in 64.3%. Overall rates of success with modification were 90% (CFP) and 89% (CFT+AK). No major treatment-emergent toxicity was reported. Monotherapy with CFP seems to be as effective and safe as the combination of CFT+AK for initial empirical therapy in children and adolescents with NF.

Improving HIV management in sub-Saharan Africa: How much palliative care is needed?

The WHO advocates palliative care as an essential component of HIV care from the point of diagnosis (when the burden of pain and symptoms may be first experienced) to the end of life and into bereavement (World Health Organisation, 2006). However, in the field of African HIV care where mortality is high, palliative care has been shown to be largely lacking. This study aimed to measure the prevalence of multidimensional palliative care needs of patients with HIV disease in Muheza, Tanzania. A prospective census measured presenting problems for all patients during a one-month period: professional contact; physical symptoms; psychosocial problems; prescribing; and care planning. During the four-week period of the study, 731 patients attended for HIV care. The total number of professional contacts was 1,512, with 736 nurse, 733 doctor and 43 social worker contacts. Patients were identified as being appropriate for palliative care if they needed pain relief other than simple paracetamol or if they or their family had complex pain or physical, psychosocial or spiritual needs. The mean patient age was 35.4 years (SD=13.7) and 82 patients were under the age of 16. The majority were female (70.9%). Morphine was being prescribed to 21 patients (2.8%) and ART was being prescribed to 434 (59.4%). The mean CD4 count was 178.3 cells mm3 (Median=131.1; SD=179.9). Palliative care intervention was indicated for 378 (51.7%) patients. Among those 434 patients using ART, 230 (52.9%) were indicated as having palliative care needs. Palliative care continues to be an important part of HIV programmes even in the presence of ARV treatment.

Glyceryl trinitrate prevents neutrophil activation but not thromboxane release following ischaemia-reperfusion injury.

The aim of this study was to determine whether glyceryl trinitrate (GTN) has a protective effect on neutrophil-mediated lung injury in a model of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with GTN (2 micrograms kg-1 min-1) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutrophil counts. Neutrophil superoxide release was measured by flow cytometry in a further IR versus GTN experiment (n = 6 in each group). The significant increase in MPO activity produced by IR to a level of 7.99 units g-1 was prevented by GTN which reduced the level to 4.73 units g-1. The increase in pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL protein without GTN was 992 micrograms ml-1 and with GTN 579 micrograms ml-1; BAL neutrophil count without GTN was 3219 cells mm-3 and with GTN 820 cells mm-3; the wet:dry lung weight ratio without GTN was 3.8 and with GTN 3.3. Neutrophil superoxide release increased significantly after 40 min of reperfusion in the untreated IR group (P < 0.05). This increase was prevented in the GTN-treated group. GTN administration had no effect on plasma thromboxane production during revascularization. These data suggest that GTN administration during the reperfusion phase has the potential to decrease pulmonary microvascular injury.